Pub Date : 2026-01-14DOI: 10.1016/j.conctc.2026.101600
Ting Lu , Zhixuan Shi , Shuna Huang , Lan Lv , Xinyuan Chen , Ke Ma , Xu Li , Fancai Lai , Jun Ni
<div><h3>Aims</h3><div>Surgery provides the best chance of survival for early-stage non-small cell lung cancer patients, resulting in a large number of patients requiring surgical resection each year. Preoperative inspiratory muscle training (IMT) is recognized as an important component of the preoperative management of lung cancer, although there is limited evidence for the delivery of a home-based IMT combined with preoperative education. We developed a programme combining short-term home-based IMT and preoperative physiotherapy education ("the programme") for lung patients with lung cancer. This study aims to evaluate the effectiveness of the programme in reducing postoperative pulmonary complications (PPCs) after video-assisted thoracoscopic surgery (VATs) compared to standard care.</div></div><div><h3>Methods</h3><div>This randomized controlled clinical trial (RCT) called for 114 participants at a tertiary hospital to be randomized 1:1 to the control group (CG) and the intervention group (IG). All subjects in both groups received routine perioperative rehabilitation intervention and health education manual. Participants in the IG received a detailed education course plus at least seven-day inspiratory muscle training programme before VATs. Outcome assessments were obtained in person at baseline (T0), the day before surgery (T1) and hospital discharge (T2). Primary outcome measure was PPCs using the Melbourne Group Score (MGS) obtained at discharge. Secondary outcomes were health-related quality of life, maximal inspiratory pressure (MIP), Forced expiratory volume in the first second (FEV1), 6-min walk distance (6MWD), length of hospital stay (LOS), anxiety and depression levels, and hospital costs. SPSS 26.0 statistical analysis software was used for analysis, and bilateral tests were used according to statistical tests. When P < 0.05, the difference was considered statistically significant.</div></div><div><h3>Results</h3><div>In accordance with the protocol, we performed interim unblinding after 50 % of the patients had been enrolled. At the interim analysis, the conditional power was calculated as 0.035 (futility index: 0.965; Supplementary 1), indicating this study should be stopped because there is little chance of achieving statistical significance. No safety concerns were identified. A total of 56 cases (27 cases in the IG and 29 cases in the CG) were finally included from March 2023 to March 2024. The incidence of PPCs between the two groups was not statistically significant (CG = 2/29, IG = 3/27, adjust RR was1.90 (0.29–12.82). One-week preoperative training programme increased MIP, but the results were not sufficient to make a significant difference (P = 0.208). Other secondary outcome measures were also assessed, but no significant between-group differences were found.</div></div><div><h3>Conclusion</h3><div>Preoperative education combined with one-week IMT has no significant clinical significance in reducing the incidence of p
{"title":"Effect of preoperative inspiratory muscle training combined with education course on postoperative pulmonary complications in high-risk patients with lung cancer after video-assisted thoracoscopic surgery: a randomized controlled trial","authors":"Ting Lu , Zhixuan Shi , Shuna Huang , Lan Lv , Xinyuan Chen , Ke Ma , Xu Li , Fancai Lai , Jun Ni","doi":"10.1016/j.conctc.2026.101600","DOIUrl":"10.1016/j.conctc.2026.101600","url":null,"abstract":"<div><h3>Aims</h3><div>Surgery provides the best chance of survival for early-stage non-small cell lung cancer patients, resulting in a large number of patients requiring surgical resection each year. Preoperative inspiratory muscle training (IMT) is recognized as an important component of the preoperative management of lung cancer, although there is limited evidence for the delivery of a home-based IMT combined with preoperative education. We developed a programme combining short-term home-based IMT and preoperative physiotherapy education (\"the programme\") for lung patients with lung cancer. This study aims to evaluate the effectiveness of the programme in reducing postoperative pulmonary complications (PPCs) after video-assisted thoracoscopic surgery (VATs) compared to standard care.</div></div><div><h3>Methods</h3><div>This randomized controlled clinical trial (RCT) called for 114 participants at a tertiary hospital to be randomized 1:1 to the control group (CG) and the intervention group (IG). All subjects in both groups received routine perioperative rehabilitation intervention and health education manual. Participants in the IG received a detailed education course plus at least seven-day inspiratory muscle training programme before VATs. Outcome assessments were obtained in person at baseline (T0), the day before surgery (T1) and hospital discharge (T2). Primary outcome measure was PPCs using the Melbourne Group Score (MGS) obtained at discharge. Secondary outcomes were health-related quality of life, maximal inspiratory pressure (MIP), Forced expiratory volume in the first second (FEV1), 6-min walk distance (6MWD), length of hospital stay (LOS), anxiety and depression levels, and hospital costs. SPSS 26.0 statistical analysis software was used for analysis, and bilateral tests were used according to statistical tests. When P < 0.05, the difference was considered statistically significant.</div></div><div><h3>Results</h3><div>In accordance with the protocol, we performed interim unblinding after 50 % of the patients had been enrolled. At the interim analysis, the conditional power was calculated as 0.035 (futility index: 0.965; Supplementary 1), indicating this study should be stopped because there is little chance of achieving statistical significance. No safety concerns were identified. A total of 56 cases (27 cases in the IG and 29 cases in the CG) were finally included from March 2023 to March 2024. The incidence of PPCs between the two groups was not statistically significant (CG = 2/29, IG = 3/27, adjust RR was1.90 (0.29–12.82). One-week preoperative training programme increased MIP, but the results were not sufficient to make a significant difference (P = 0.208). Other secondary outcome measures were also assessed, but no significant between-group differences were found.</div></div><div><h3>Conclusion</h3><div>Preoperative education combined with one-week IMT has no significant clinical significance in reducing the incidence of p","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101600"},"PeriodicalIF":1.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.conctc.2026.101598
Carmen P. McLean , Meghan M. Bell , Christopher K. Haddock , Stefanie T. LoSavio , Jeffrey Mann , Shannon McCaslin , Nazia Rahman , Lauren Rodden , Timothy Rogers , Craig S. Rosen , Craig Woodworth , Jeffrey Cook
Posttraumatic stress disorder (PTSD) affects up to 13–17 % of active duty military personnel who deployed after 9/11 and significantly impacts military readiness. However, behavioral health providers in the Military Health System (MHS) face significant challenges in implementing evidence-based psychotherapies (EBPs) such as Written Exposure Therapy (WET). One of the main obstacles is the limited capacity to schedule and conduct weekly therapy sessions due to large patient panels and heavy workloads. This study uses a Hybrid Type 1 implementation-effectiveness design to increase access to WET by task sharing delivery with behavioral health technicians (BHTs). We will compare BHT-delivered WET plus treatment as usual (TAU) to TAU alone in a Phase II randomized clinical trial with 150 active-duty participants. The primary aims are to evaluate the clinical effectiveness of BHT-delivered WET, patient acceptability, and BHT treatment fidelity. Secondary aims include identifying barriers and facilitators to WET implementation. Participants will be randomly assigned to BHT-delivered WET or TAU alone, with WET delivered weekly over five sessions either in-person or via telehealth. Quality control will be maintained through rigorous BHT training, supervision, and fidelity assessments. Community-Based Participatory Research methods will ensure stakeholder engagement and feedback throughout the study. Data analysis involves linear mixed-effects models and rapid qualitative analysis to assess outcomes. The results will demonstrate the effectiveness of WET in routine care settings and the feasibility of BHT-delivered WET as an implementation strategy. The findings have the potential to enhance PTSD treatment accessibility and inform best practices within the MHS and similar settings.
{"title":"Behavioral health technician delivered written exposure therapy for posttraumatic stress disorder in the military: Design of a hybrid implementation effectiveness trial","authors":"Carmen P. McLean , Meghan M. Bell , Christopher K. Haddock , Stefanie T. LoSavio , Jeffrey Mann , Shannon McCaslin , Nazia Rahman , Lauren Rodden , Timothy Rogers , Craig S. Rosen , Craig Woodworth , Jeffrey Cook","doi":"10.1016/j.conctc.2026.101598","DOIUrl":"10.1016/j.conctc.2026.101598","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) affects up to 13–17 % of active duty military personnel who deployed after 9/11 and significantly impacts military readiness. However, behavioral health providers in the Military Health System (MHS) face significant challenges in implementing evidence-based psychotherapies (EBPs) such as Written Exposure Therapy (WET). One of the main obstacles is the limited capacity to schedule and conduct weekly therapy sessions due to large patient panels and heavy workloads. This study uses a Hybrid Type 1 implementation-effectiveness design to increase access to WET by task sharing delivery with behavioral health technicians (BHTs). We will compare BHT-delivered WET plus treatment as usual (TAU) to TAU alone in a Phase II randomized clinical trial with 150 active-duty participants. The primary aims are to evaluate the clinical effectiveness of BHT-delivered WET, patient acceptability, and BHT treatment fidelity. Secondary aims include identifying barriers and facilitators to WET implementation. Participants will be randomly assigned to BHT-delivered WET or TAU alone, with WET delivered weekly over five sessions either in-person or via telehealth. Quality control will be maintained through rigorous BHT training, supervision, and fidelity assessments. Community-Based Participatory Research methods will ensure stakeholder engagement and feedback throughout the study. Data analysis involves linear mixed-effects models and rapid qualitative analysis to assess outcomes. The results will demonstrate the effectiveness of WET in routine care settings and the feasibility of BHT-delivered WET as an implementation strategy. The findings have the potential to enhance PTSD treatment accessibility and inform best practices within the MHS and similar settings.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101598"},"PeriodicalIF":1.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.conctc.2026.101597
Alexandria M. Boykins , Asos Mahmood , Mona N. Wicks , Satya Surbhi , Santos A. Martinez , Frankie B. Stentz , James E. Bailey
Background
Intensive lifestyle programs promoting weight loss have been shown to induce long-term remission of early Type 2 diabetes (T2D). Further, multicomponent weight loss interventions are recommended for all patients with obesity, but these programs are largely unavailable for people living in low-income and medically underserved areas in the United States (US) and little is known about the benefits, feasibility, and costs of such interventions in community settings.
Objective
To assess the feasibility, preliminary effectiveness, and costs of a multicomponent intensive healthy eating and weight-loss program designed to support diabetes remission.
Study design
The US-based Healthy Eating and Active Living to reverse diabetes (HEAL Diabetes-USA) is a pragmatic randomized controlled pilot study conducted in Memphis, Tennessee (data collection: August 2023–August 2025), independent of and not affiliated with the UK-based HEAL-D program. Adults (≥18 years) with early T2D (<6 years), HbA1c ≥ 6.5%, and overweight/obesity (n = 60) are randomized to either Enhanced Care (EC) or Intensive Care (IC). EC includes printed materials and standard health coaching. IC is the multi-component intervention arm which includes grocery delivery, nutrition education, biweekly group sessions, and ongoing health coaching. Primary outcomes include changes in body weight and HbA1c, and proportion of patients who achieved diabetes remission at 6 and 12 months. Secondary outcomes include changes in random blood glucose, self-efficacy, diabetes self-care activities and program cost analyses.
Conclusions
This protocol describes the design of HEAL Diabetes-USA, a community-based intensive lifestyle intervention for early T2D. Findings will inform the feasibility and cost-effectiveness of delivering multicomponent diabetes-remission programs in medically underserved US settings.
{"title":"Healthy eating and active living to reverse diabetes (HEAL Diabetes-USA): a randomized controlled pilot study protocol to assess the feasibility of a weight loss intervention for diabetes remission","authors":"Alexandria M. Boykins , Asos Mahmood , Mona N. Wicks , Satya Surbhi , Santos A. Martinez , Frankie B. Stentz , James E. Bailey","doi":"10.1016/j.conctc.2026.101597","DOIUrl":"10.1016/j.conctc.2026.101597","url":null,"abstract":"<div><h3>Background</h3><div>Intensive lifestyle programs promoting weight loss have been shown to induce long-term remission of early Type 2 diabetes (T2D). Further, multicomponent weight loss interventions are recommended for all patients with obesity, but these programs are largely unavailable for people living in low-income and medically underserved areas in the United States (US) and little is known about the benefits, feasibility, and costs of such interventions in community settings.</div></div><div><h3>Objective</h3><div>To assess the feasibility, preliminary effectiveness, and costs of a multicomponent intensive healthy eating and weight-loss program designed to support diabetes remission.</div></div><div><h3>Study design</h3><div>The US-based Healthy Eating and Active Living to reverse diabetes (HEAL Diabetes-USA) is a pragmatic randomized controlled pilot study conducted in Memphis, Tennessee (data collection: August 2023–August 2025), independent of and not affiliated with the UK-based HEAL-D program. Adults (≥18 years) with early T2D (<6 years), HbA1c ≥ 6.5%, and overweight/obesity (n = 60) are randomized to either Enhanced Care (EC) or Intensive Care (IC). EC includes printed materials and standard health coaching. IC is the multi-component intervention arm which includes grocery delivery, nutrition education, biweekly group sessions, and ongoing health coaching. Primary outcomes include changes in body weight and HbA1c, and proportion of patients who achieved diabetes remission at 6 and 12 months. Secondary outcomes include changes in random blood glucose, self-efficacy, diabetes self-care activities and program cost analyses.</div></div><div><h3>Conclusions</h3><div>This protocol describes the design of HEAL Diabetes-USA, a community-based intensive lifestyle intervention for early T2D. Findings will inform the feasibility and cost-effectiveness of delivering multicomponent diabetes-remission programs in medically underserved US settings.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101597"},"PeriodicalIF":1.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.conctc.2026.101596
Charlie Olvera , Vanessa Ramirez-Zohfeld , Alaine Murawski , Angela Fidler Pfammatter , Lee A. Lindquist
Traditional clinical trial designs such as the isolated two-arm randomized controlled trial (RCT) do not offer robust solutions for evaluating and optimizing delivery of complex, multi-component behavioral interventions. A recent alternative design, the Multiphase Optimization Strategy (MOST), addresses many shortcomings of the isolated two-arm RCT. The MOST framework for trial design provides researchers opportunities to perform independent evaluations of intervention content, dosage levels, delivery formats, and potential intra-intervention interactions. Results from factorial trials which implement MOST frameworks are used to optimize ongoing interventions.
Herein, we describe the protocol for a MOST RCT which evaluates NegotiAge, an artificial intelligence-based negotiation and dispute resolution training program for family caregivers of older adults. Many family caregivers experience conflicts as they support older adult care recipients. Teaching negotiation skills to family caregivers has potential to improve communication and resolve conflicts more efficiently. The trial evaluation of NegotiAge eschews traditional two-arm RCT design and instead employs the MOST framework. Our MOST trial tests eight treatment combination packages against one another and evaluates associations between specific treatment combinations and user-centered outcomes.
This research is the first to apply the MOST framework in geriatrics and family caregiving. Our use of the MOST framework to evaluate and optimize NegotiAge enables us to identify which components are most effective for family caregivers and isolate the interactional effects of each component. The protocol and eventual results of our MOST trial will demonstrate how to optimize an intervention to be efficient and potent for busy family caregivers of older adults.
{"title":"Evaluating a negotiation training program for family caregivers of older people using a Multiphase Optimization Strategy (MOST) design and protocol","authors":"Charlie Olvera , Vanessa Ramirez-Zohfeld , Alaine Murawski , Angela Fidler Pfammatter , Lee A. Lindquist","doi":"10.1016/j.conctc.2026.101596","DOIUrl":"10.1016/j.conctc.2026.101596","url":null,"abstract":"<div><div>Traditional clinical trial designs such as the isolated two-arm randomized controlled trial (RCT) do not offer robust solutions for evaluating and optimizing delivery of complex, multi-component behavioral interventions. A recent alternative design, the Multiphase Optimization Strategy (MOST), addresses many shortcomings of the isolated two-arm RCT. The MOST framework for trial design provides researchers opportunities to perform independent evaluations of intervention content, dosage levels, delivery formats, and potential intra-intervention interactions. Results from factorial trials which implement MOST frameworks are used to optimize ongoing interventions.</div><div>Herein, we describe the protocol for a MOST RCT which evaluates NegotiAge, an artificial intelligence-based negotiation and dispute resolution training program for family caregivers of older adults. Many family caregivers experience conflicts as they support older adult care recipients. Teaching negotiation skills to family caregivers has potential to improve communication and resolve conflicts more efficiently. The trial evaluation of NegotiAge eschews traditional two-arm RCT design and instead employs the MOST framework. Our MOST trial tests eight treatment combination packages against one another and evaluates associations between specific treatment combinations and user-centered outcomes.</div><div>This research is the first to apply the MOST framework in geriatrics and family caregiving. Our use of the MOST framework to evaluate and optimize NegotiAge enables us to identify which components are most effective for family caregivers and isolate the interactional effects of each component. The protocol and eventual results of our MOST trial will demonstrate how to optimize an intervention to be efficient and potent for busy family caregivers of older adults.</div></div><div><h3>Trial registration ID</h3><div>NCT04837937.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101596"},"PeriodicalIF":1.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-10DOI: 10.1016/j.conctc.2026.101595
Catherine F. Siengsukon , Jade Robichaud , Eryen Nelson , Allison Glaser , Garrett R. Baber , Matthew K.P. Gratton , Anna Zanotto , Milind A. Phadnis , Sharon Lynch
Insomnia is a common problem for individuals with multiple sclerosis (MS) occurring in at least 40 % of individuals with MS. Sleep disturbances in people with MS have been associated with a reduction in cognitive performance, physical function, psychological well-being, quality of life, and occupational function, as well as increased prevalence of fatigue, pain, depression, and anxiety. Cognitive behavioral therapy for insomnia (CBT-I), a multicomponent treatment strategy, addresses thoughts and behaviors that can negatively impact sleep and is the recommended treatment for chronic insomnia. CBT-I is shown to be more effective than pharmacological interventions long-term for treating insomnia with improvements remaining up to 10 years following CBT-I. However, there are limited studies that have examined the effect of CBT-I on sleep outcomes and comorbid symptoms in people with MS. The objective of the proposed study is to determine the efficacy of CBT-I delivered via telehealth to improve insomnia symptoms, fatigue, and health-related quality of life in people with MS. CBT-I offers a low-risk, cost-effective, non-pharmacological approach to improving sleep quality, fatigue, and daily functioning in individuals with MS. Targeting insomnia in MS may also reduce disability, enhance quality of life, increase employment rates, and lower healthcare and support costs. Furthermore, understanding factors that impact improvement in outcomes will allow more accurate individualization of insomnia treatment for people with MS.
Trial registration
The CALM study is registered at: https://clinicaltrials.gov (NCT06428006).
{"title":"Cognitive behavioral therapy for insomnia for individuals with multiple sclerosis (CALM): A randomized control trial protocol","authors":"Catherine F. Siengsukon , Jade Robichaud , Eryen Nelson , Allison Glaser , Garrett R. Baber , Matthew K.P. Gratton , Anna Zanotto , Milind A. Phadnis , Sharon Lynch","doi":"10.1016/j.conctc.2026.101595","DOIUrl":"10.1016/j.conctc.2026.101595","url":null,"abstract":"<div><div>Insomnia is a common problem for individuals with multiple sclerosis (MS) occurring in at least 40 % of individuals with MS. Sleep disturbances in people with MS have been associated with a reduction in cognitive performance, physical function, psychological well-being, quality of life, and occupational function, as well as increased prevalence of fatigue, pain, depression, and anxiety. Cognitive behavioral therapy for insomnia (CBT-I), a multicomponent treatment strategy, addresses thoughts and behaviors that can negatively impact sleep and is the recommended treatment for chronic insomnia. CBT-I is shown to be more effective than pharmacological interventions long-term for treating insomnia with improvements remaining up to 10 years following CBT-I. However, there are limited studies that have examined the effect of CBT-I on sleep outcomes and comorbid symptoms in people with MS. The objective of the proposed study is to determine the efficacy of CBT-I delivered via telehealth to improve insomnia symptoms, fatigue, and health-related quality of life in people with MS. CBT-I offers a low-risk, cost-effective, non-pharmacological approach to improving sleep quality, fatigue, and daily functioning in individuals with MS. Targeting insomnia in MS may also reduce disability, enhance quality of life, increase employment rates, and lower healthcare and support costs. Furthermore, understanding factors that impact improvement in outcomes will allow more accurate individualization of insomnia treatment for people with MS.</div></div><div><h3>Trial registration</h3><div>The CALM study is registered at: <span><span>https://clinicaltrials.gov</span><svg><path></path></svg></span> (NCT06428006).</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101595"},"PeriodicalIF":1.4,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1016/j.conctc.2026.101594
Benjamin T. Hayes , Annika Sabado , Haruka Minami , Chenshu Zhang , Matthew Holm , Laila Khalid , Tiffany Y. Lu , Kristine Torres-Lockhart , Aaron D. Fox
Background
Buprenorphine is an effective treatment for opioid use disorder (OUD), however withdrawal during initiation is a barrier. Low-dose initiation (LDI) involves starting very small doses of buprenorphine overlapping with opioids to avoid withdrawal. This pilot study aims to evaluate the feasibility of a randomized controlled trial (RCT) comparing buprenorphine LDI versus standard initiation among ambulatory patients with OUD.
Methods
This is a pragmatic parallel-group open-label pilot RCT of LDI versus standard initiation in ambulatory settings. LDI arm: starts with 0.5–0.125 mg of sublingual buprenorphine-naloxone films daily, titrating to a therapeutic dose over eight days. Standard arm: participants achieve moderate withdrawal before beginning with 4–1 mg. Therapeutic target in both arms:16-4 mg to 32-8 mg. A total of 70 adults (18 years or older) with any severity of OUD will be recruited. Key exclusion includes currently taking medication treatment for OUD, severe alcohol or benzodiazepine use disorder, severe mental illness, and pregnancy. The primary outcome: feasibility of recruiting primary care patients with OUD to a clinical trial of LDI, measured as percent of assessed participants who enroll in the study. Key secondary outcomes: LDI protocol feasibility, meaning compliance to the protocol (i.e., starting with less than 1 mg of buprenorphine and taking increasing dosages daily); preliminary effectiveness of treatment uptake at a two-week study visit, confirmed by a urine drug test positive for buprenorphine; six-week treatment retention measured by pharmacy-dispensed buprenorphine; and safety outcomes.
Discussion
As a pilot clinical trial this study will inform design of a fully powered RCT to test buprenorphine LDI in the ambulatory setting.
Trial registrationClinicalTrials.gov, NCT05450718: date of registration: June 22, 2022; https://clinicaltrials.gov/study/NCT05450718?term=NCT05450718&rank=1.
{"title":"MiBUP: A pilot randomized controlled trial of low-dose initiation of buprenorphine for opioid use disorder: Design and rationale","authors":"Benjamin T. Hayes , Annika Sabado , Haruka Minami , Chenshu Zhang , Matthew Holm , Laila Khalid , Tiffany Y. Lu , Kristine Torres-Lockhart , Aaron D. Fox","doi":"10.1016/j.conctc.2026.101594","DOIUrl":"10.1016/j.conctc.2026.101594","url":null,"abstract":"<div><h3>Background</h3><div>Buprenorphine is an effective treatment for opioid use disorder (OUD), however withdrawal during initiation is a barrier. Low-dose initiation (LDI) involves starting very small doses of buprenorphine overlapping with opioids to avoid withdrawal. This pilot study aims to evaluate the feasibility of a randomized controlled trial (RCT) comparing buprenorphine LDI versus standard initiation among ambulatory patients with OUD.</div></div><div><h3>Methods</h3><div>This is a pragmatic parallel-group open-label pilot RCT of LDI versus standard initiation in ambulatory settings. LDI arm: starts with 0.5–0.125 mg of sublingual buprenorphine-naloxone films daily, titrating to a therapeutic dose over eight days. Standard arm: participants achieve moderate withdrawal before beginning with 4–1 mg. Therapeutic target in both arms:16-4 mg to 32-8 mg. A total of 70 adults (18 years or older) with any severity of OUD will be recruited. Key exclusion includes currently taking medication treatment for OUD, severe alcohol or benzodiazepine use disorder, severe mental illness, and pregnancy. The primary outcome: feasibility of recruiting primary care patients with OUD to a clinical trial of LDI, measured as percent of assessed participants who enroll in the study. Key secondary outcomes: LDI protocol feasibility, meaning compliance to the protocol (i.e., starting with less than 1 mg of buprenorphine and taking increasing dosages daily); preliminary effectiveness of treatment uptake at a two-week study visit, confirmed by a urine drug test positive for buprenorphine; six-week treatment retention measured by pharmacy-dispensed buprenorphine; and safety outcomes.</div></div><div><h3>Discussion</h3><div>As a pilot clinical trial this study will inform design of a fully powered RCT to test buprenorphine LDI in the ambulatory setting.</div><div><em>Trial registration</em> <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, NCT05450718: date of registration: June 22, 2022; <span><span>https://clinicaltrials.gov/study/NCT05450718?term=NCT05450718&rank=1</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101594"},"PeriodicalIF":1.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.conctc.2025.101590
Adetayo Kasim , Marina Anastasiou , Evangelia Loizou , Andreas Dimakakos , Maria Georganaki , Ioannis Mourelatos , Panos Karelis , Marianna Esposito , Helen Zhou , Tai-Tsang Chen , Dimitrios Skaltsas , Paul Stockman
Background
This study examines whether single-agent activity in early clinical phases correlates with the approval likelihood of combination therapies in oncology. Using the Intelligencia AI database, we investigated the impact of monotherapy efficacy on the success rates of combination therapies.
Methods
The analysis included combinational therapies across various solid tumor types, assessing the approval rates and the presence of monotherapy efficacy with cut-off date September 12, 2024, and an assessment of 3896 programs. We analyzed historical clinical trial data focusing on Objective Response Rate (ORR) as a metric of single-agent activity (SAA).
Results
Approval rate for combination programs across all indications and phases was 4.2 %. Programs that included approved monotherapy drugs had an approval rate of 6.1 %, whereas those without approved monotherapy drugs had a lower approval rate of 2.7 %. However, the historical approval rate for combination programs with failed monotherapy drug with more than 20 % objective response rate was 5.8 %. Furthermore, approved combinations derived from monotherapy-failed pipelines showed diverse ORR thresholds, with specific trends observed across different cancer types.
Conclusions
The likelihood of approval for combination therapies is higher when combined with monotherapy drugs that have previously shown single agent activity. This finding is consistent with other research on historical approval rates and the common consensus within oncology drug development. Here we suggest that by leveraging monotherapy drug activity there can be an enhanced prioritization of anti-cancer agents repurposed for combination therapies, which would have otherwise been shelved based on their single agent failure.
{"title":"Strategic risk assessment in oncology: Utilizing single-agent activity to boost combination therapy approvals","authors":"Adetayo Kasim , Marina Anastasiou , Evangelia Loizou , Andreas Dimakakos , Maria Georganaki , Ioannis Mourelatos , Panos Karelis , Marianna Esposito , Helen Zhou , Tai-Tsang Chen , Dimitrios Skaltsas , Paul Stockman","doi":"10.1016/j.conctc.2025.101590","DOIUrl":"10.1016/j.conctc.2025.101590","url":null,"abstract":"<div><h3>Background</h3><div>This study examines whether single-agent activity in early clinical phases correlates with the approval likelihood of combination therapies in oncology. Using the Intelligencia AI database, we investigated the impact of monotherapy efficacy on the success rates of combination therapies.</div></div><div><h3>Methods</h3><div>The analysis included combinational therapies across various solid tumor types, assessing the approval rates and the presence of monotherapy efficacy with cut-off date September 12, 2024, and an assessment of 3896 programs. We analyzed historical clinical trial data focusing on Objective Response Rate (ORR) as a metric of single-agent activity (SAA).</div></div><div><h3>Results</h3><div>Approval rate for combination programs across all indications and phases was 4.2 %. Programs that included approved monotherapy drugs had an approval rate of 6.1 %, whereas those without approved monotherapy drugs had a lower approval rate of 2.7 %. However, the historical approval rate for combination programs with failed monotherapy drug with more than 20 % objective response rate was 5.8 %. Furthermore, approved combinations derived from monotherapy-failed pipelines showed diverse ORR thresholds, with specific trends observed across different cancer types.</div></div><div><h3>Conclusions</h3><div>The likelihood of approval for combination therapies is higher when combined with monotherapy drugs that have previously shown single agent activity. This finding is consistent with other research on historical approval rates and the common consensus within oncology drug development. Here we suggest that by leveraging monotherapy drug activity there can be an enhanced prioritization of anti-cancer agents repurposed for combination therapies, which would have otherwise been shelved based on their single agent failure.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101590"},"PeriodicalIF":1.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.conctc.2025.101592
Jiayi Hu , Abdel G. Babiker , Cavan S. Reilly , Jason V. Baker , Lianne K. Siegel , STRIVE OTAC Study Group
The recent growth of immunoglobulin-based therapies has motivated clinical trials testing primary endpoints both in the overall cohort and in subgroups of patients, such as in patients without specific antibodies at baseline. Multiple testing methods in clinical trials often ignore the natural correlation between test statistics in such contexts, resulting in overly conservative type I error control. The Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) trial, is an ongoing Phase III trial evaluating the effect of a single infusion of anti-COVID-19 hyperimmune intravenous immunoglobulin (hIVIG), in outpatient adults with recently diagnosed SARS-CoV-2 infection, in both the overall cohort and in the subgroup of participants who had not received monoclonal antibodies or antiviral treatments. We present the method used to control the type I error at a predetermined rate while taking the estimated correlation into account, thus increasing efficiency. We evaluated the operating characteristics of this method in both fixed and group-sequential scenarios through extensive simulation studies. Our findings indicate that this approach controls the type I error at the desired rate, improves power, and reduces the expected sample size compared to a Bonferroni correction. Trial Registration: This study was registered on clinicaltrials.gov under NCT0491026 on 1 June 2021.
{"title":"Type I error control and interim monitoring for co-primary hypotheses involving a subgroup in the Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) trial","authors":"Jiayi Hu , Abdel G. Babiker , Cavan S. Reilly , Jason V. Baker , Lianne K. Siegel , STRIVE OTAC Study Group","doi":"10.1016/j.conctc.2025.101592","DOIUrl":"10.1016/j.conctc.2025.101592","url":null,"abstract":"<div><div>The recent growth of immunoglobulin-based therapies has motivated clinical trials testing primary endpoints both in the overall cohort and in subgroups of patients, such as in patients without specific antibodies at baseline. Multiple testing methods in clinical trials often ignore the natural correlation between test statistics in such contexts, resulting in overly conservative type I error control. The Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) trial, is an ongoing Phase III trial evaluating the effect of a single infusion of anti-COVID-19 hyperimmune intravenous immunoglobulin (hIVIG), in outpatient adults with recently diagnosed SARS-CoV-2 infection, in both the overall cohort and in the subgroup of participants who had not received monoclonal antibodies or antiviral treatments. We present the method used to control the type I error at a predetermined rate while taking the estimated correlation into account, thus increasing efficiency. We evaluated the operating characteristics of this method in both fixed and group-sequential scenarios through extensive simulation studies. Our findings indicate that this approach controls the type I error at the desired rate, improves power, and reduces the expected sample size compared to a Bonferroni correction. <strong>Trial Registration</strong>: This study was registered on clinicaltrials.gov under NCT0491026 on 1 June 2021.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101592"},"PeriodicalIF":1.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.conctc.2025.101593
Ugur Sener , Taylor Galloway , Bryan Neth , Joon Uhm , Sani H. Kizilbash , Jian L. Campian , Samantha Caron , William G. Breen , Eric Lehrer , Elizabeth Golembiewski , Sydney Schultz , Heather Hughes , Sue Steinmetz , Susan Geyer , Carolyn Mead-Harvey , Carey Huebert , William Tauer , Charles Mason , Terry C. Burns , Joshua Pritchett , Tufia Haddad
Care at high volume centers is associated with an overall survival benefit for patients with glioma. However, access to these centers is challenging for patients who experience neurologic deficits, leading to loss of independence and rendering travel difficult. Patients with low socio-economic status (SES) often lack logistical resources for travel, leading to poorer outcomes. There is a critical need for scalable telehealth solutions to increase access to specialized care. The Neuro-Oncology Anywhere 242 study systematically compares telehealth and in-person neuro-oncology assessments, as decentralization of care delivery may enable glioma patients with neurologic deficits and low SES to access specialized care and experience improved health outcomes. The primary objective of this study is to assess patient satisfaction with care delivered as measured by institutional Press-Ganey survey scores obtained following telehealth and in-person assessments. A key secondary objective is to assess the completion rate of planned oral chemotherapy among patients with glioma within 28 days of telehealth visits compared to in-person visits. Chemotherapy adherence is evaluated using a novel digital pill diary that has been developed for this study. Other secondary objectives include preference for telehealth versus in-person evaluations as well as acute care utilization, neurologic impairment, and quality of life among participants after telehealth versus in-person visits. Successful demonstration of this will offer a strong scientific rationale to incorporate telehealth into interventional clinical trials to accelerate development of novel therapeutics unconstrained by geographic location, disability, or SES.
{"title":"Protocol for neuro-oncology anywhere 242: Pilot study evaluating telehealth and in-person assessments in patients with glioma receiving oral chemotherapy","authors":"Ugur Sener , Taylor Galloway , Bryan Neth , Joon Uhm , Sani H. Kizilbash , Jian L. Campian , Samantha Caron , William G. Breen , Eric Lehrer , Elizabeth Golembiewski , Sydney Schultz , Heather Hughes , Sue Steinmetz , Susan Geyer , Carolyn Mead-Harvey , Carey Huebert , William Tauer , Charles Mason , Terry C. Burns , Joshua Pritchett , Tufia Haddad","doi":"10.1016/j.conctc.2025.101593","DOIUrl":"10.1016/j.conctc.2025.101593","url":null,"abstract":"<div><div>Care at high volume centers is associated with an overall survival benefit for patients with glioma. However, access to these centers is challenging for patients who experience neurologic deficits, leading to loss of independence and rendering travel difficult. Patients with low socio-economic status (SES) often lack logistical resources for travel, leading to poorer outcomes. There is a critical need for scalable telehealth solutions to increase access to specialized care. The Neuro-Oncology Anywhere 242 study systematically compares telehealth and in-person neuro-oncology assessments, as decentralization of care delivery may enable glioma patients with neurologic deficits and low SES to access specialized care and experience improved health outcomes. The primary objective of this study is to assess patient satisfaction with care delivered as measured by institutional Press-Ganey survey scores obtained following telehealth and in-person assessments. A key secondary objective is to assess the completion rate of planned oral chemotherapy among patients with glioma within 28 days of telehealth visits compared to in-person visits. Chemotherapy adherence is evaluated using a novel digital pill diary that has been developed for this study. Other secondary objectives include preference for telehealth versus in-person evaluations as well as acute care utilization, neurologic impairment, and quality of life among participants after telehealth versus in-person visits. Successful demonstration of this will offer a strong scientific rationale to incorporate telehealth into interventional clinical trials to accelerate development of novel therapeutics unconstrained by geographic location, disability, or SES.</div></div><div><h3>Trial registration id</h3><div><span><span>NCT06625047</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101593"},"PeriodicalIF":1.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.conctc.2025.101591
Sonalee A. Joshi, Tao Lin, Nicholas L. Balderston, Kevin G. Lynch, Mingcong Tang, Milan Patel, Ivy Sun, Barbara Fureman, Desmond J. Oathes, David F. Gregory, Yvette I. Sheline, Lily A. Brown
Post-traumatic stress disorder (PTSD) links to impaired extinction learning post-trauma. While treatments like prolonged exposure therapy improve this learning, they benefit only 40–60 % of patients. Optimal arousal supports extinction learning, but excessive arousal can hinder it. The intraparietal sulcus (IPS) is involved in arousal regulation but has not yet been targeted using continuous theta burst stimulation (cTBS) in PTSD. This study is the first to explore the effect of IPS cTBS on extinction learning in PTSD. This study aims to 1) evaluate the impact of IPS cTBS on anxiety potentiated startle (APS) among patients with PTSD compared to sham IPS cTBS, 2) examine whether IPS cTBS improves extinction learning relative to neutral learning, and 3) identify the ideal dose of cTBS. Adults with PTSD will participate in six visits, involving clinical assessments, functional MRI (fMRI), and IPS cTBS. Participants will undergo diagnostic interviews, generate trauma and neutral scripts, and complete script-driven imagery tasks. They will receive active or sham cTBS (counterbalanced) paired with trauma or neutral scripts during separate visits. Follow-up assessments occur at 24 h and 30 days post-intervention. IRB approval and preliminary preparations began in January 2024. Recruitment started in April 2024 and is projected to conclude by April 2028. Ethical procedures are approved by the University of Pennsylvania IRB (Protocol Number: 849571). This will be the first study to evaluate the synergistic effects of extinction training with IPS cTBS in individuals with PTSD. Our findings will strengthen the neurobiological basis of augmenting extinction training with IPS cTBS.
{"title":"A mechanistic trial of the neurobiology of extinction learning and intraparietal sulcus stimulation: Protocol","authors":"Sonalee A. Joshi, Tao Lin, Nicholas L. Balderston, Kevin G. Lynch, Mingcong Tang, Milan Patel, Ivy Sun, Barbara Fureman, Desmond J. Oathes, David F. Gregory, Yvette I. Sheline, Lily A. Brown","doi":"10.1016/j.conctc.2025.101591","DOIUrl":"10.1016/j.conctc.2025.101591","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) links to impaired extinction learning post-trauma. While treatments like prolonged exposure therapy improve this learning, they benefit only 40–60 % of patients. Optimal arousal supports extinction learning, but excessive arousal can hinder it. The intraparietal sulcus (IPS) is involved in arousal regulation but has not yet been targeted using continuous theta burst stimulation (cTBS) in PTSD. This study is the first to explore the effect of IPS cTBS on extinction learning in PTSD. This study aims to 1) evaluate the impact of IPS cTBS on anxiety potentiated startle (APS) among patients with PTSD compared to sham IPS cTBS, 2) examine whether IPS cTBS improves extinction learning relative to neutral learning, and 3) identify the ideal dose of cTBS. Adults with PTSD will participate in six visits, involving clinical assessments, functional MRI (fMRI), and IPS cTBS. Participants will undergo diagnostic interviews, generate trauma and neutral scripts, and complete script-driven imagery tasks. They will receive active or sham cTBS (counterbalanced) paired with trauma or neutral scripts during separate visits. Follow-up assessments occur at 24 h and 30 days post-intervention. IRB approval and preliminary preparations began in January 2024. Recruitment started in April 2024 and is projected to conclude by April 2028. Ethical procedures are approved by the University of Pennsylvania IRB (Protocol Number: 849571). This will be the first study to evaluate the synergistic effects of extinction training with IPS cTBS in individuals with PTSD. Our findings will strengthen the neurobiological basis of augmenting extinction training with IPS cTBS.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101591"},"PeriodicalIF":1.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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