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}
Pub Date : 2025-12-12DOI: 10.1016/j.conctc.2025.101585
Wen-Han Li , Dong-Chen Xu , Xi-Yue Lu , Jin-Ye Ma , Fang-Fang Chen , Hao Wang , Hao Li , Zhan-Fei Tan
Background
Acute respiratory viral infections are the most common diseases affecting the respiratory system. Currently, there is still a lack of specific antiviral drugs targeting various viruses. Traditional Chinese herbal medicine, with its diverse components and multiple therapeutic targets, has emerged as a promising treatment option. "Antitoxin and Antipyretic Decoction" (AAD) is a traditional herbal formula that has been reported to effectively reduce fever and alleviate associated symptoms in clinical practice. However, there is insufficient clinical research evaluating AAD for the treatment of acute respiratory viral infections. Therefore, this study is designed to assess the efficacy of AAD in treating acute respiratory viral infections.
Methods
This is a single-center, randomized, double-blind, controlled trial. A total of 120 eligible patients will be randomly assigned in a 1:1 ratio to receive either AAD granules or placebo granules. The trial will last for 5 days, with follow-ups on days 3, 6, and 12. The primary outcome is the proportion of participants with complete fever resolution at Day 6. Secondary outcomes include time to complete fever resolution, time to initial fever reduction, use rate and average dose of emergency antipyretic medication, individual symptom scores (fever, fatigue, cough, muscle aches, taste and smell disturbances, diarrhea, nasal congestion, runny nose, headache, and fatigue) as both absolute values and change values, Traditional Chinese Medicine syndrome scores, and viral clearance time. Any adverse events occurring during the trial will be recorded by the researchers. A small-sample prospective pilot study was conducted from August 2024 to October 2024 to test the feasibility of the trial procedures; the main study described in this protocol has not yet commenced.
Discussion
This study aims to provide evidence on the efficacy and safety of AAD in the treatment of acute respiratory viral infections.
{"title":"Exploring the efficacy and safety of Antitoxin and Antipyretic Decoction in treating acute respiratory viral infections with Wind-Heat Obstruction of the Exterior and Heat Invading the Lung Defense a study protocol for a randomized controlled trial","authors":"Wen-Han Li , Dong-Chen Xu , Xi-Yue Lu , Jin-Ye Ma , Fang-Fang Chen , Hao Wang , Hao Li , Zhan-Fei Tan","doi":"10.1016/j.conctc.2025.101585","DOIUrl":"10.1016/j.conctc.2025.101585","url":null,"abstract":"<div><h3>Background</h3><div>Acute respiratory viral infections are the most common diseases affecting the respiratory system. Currently, there is still a lack of specific antiviral drugs targeting various viruses. Traditional Chinese herbal medicine, with its diverse components and multiple therapeutic targets, has emerged as a promising treatment option. \"Antitoxin and Antipyretic Decoction\" (AAD) is a traditional herbal formula that has been reported to effectively reduce fever and alleviate associated symptoms in clinical practice. However, there is insufficient clinical research evaluating AAD for the treatment of acute respiratory viral infections. Therefore, this study is designed to assess the efficacy of AAD in treating acute respiratory viral infections.</div></div><div><h3>Methods</h3><div>This is a single-center, randomized, double-blind, controlled trial. A total of 120 eligible patients will be randomly assigned in a 1:1 ratio to receive either AAD granules or placebo granules. The trial will last for 5 days, with follow-ups on days 3, 6, and 12. The primary outcome is the proportion of participants with complete fever resolution at Day 6. Secondary outcomes include time to complete fever resolution, time to initial fever reduction, use rate and average dose of emergency antipyretic medication, individual symptom scores (fever, fatigue, cough, muscle aches, taste and smell disturbances, diarrhea, nasal congestion, runny nose, headache, and fatigue) as both absolute values and change values, Traditional Chinese Medicine syndrome scores, and viral clearance time. Any adverse events occurring during the trial will be recorded by the researchers. A small-sample prospective pilot study was conducted from August 2024 to October 2024 to test the feasibility of the trial procedures; the main study described in this protocol has not yet commenced.</div></div><div><h3>Discussion</h3><div>This study aims to provide evidence on the efficacy and safety of AAD in the treatment of acute respiratory viral infections.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101585"},"PeriodicalIF":1.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791853","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 : 2025-12-05DOI: 10.1016/j.conctc.2025.101582
Nicole Cash , Mary Clare Koebel , Bashar W. Badran , Aicko Y. Schumann , Lisa M. McTeague , Thomas W. Uhde , Rodney J. Schlosser , Bernadette M. Cortese
Background
Few evidence-based treatments exist for COVID-related persistent smell dysfunction. While smell/olfactory training (ST) has emerged as a widely prescribed, first line treatment, rigorous study is required to determine its efficacy in Long COVID. Additional study and development of adjunctive methods to improve the efficacy of ST is also needed.
Methods
This paper details the study design and methodology for a large, at-home, randomized, controlled trial designed to determine whether ST and/or trigeminal nerve stimulation (TNS)-enhanced ST improves Long COVID-related disturbances in smell function, mood, sleep, and cognition. Adults with COVID-related persistent smell dysfunction (N = 180) will be recruited and randomized to self-administer ST, placebo smell training (PBO), or TNS-enhanced ST daily for 12 weeks. Our primary objectives are to i) determine the efficacy of ST, compared to any natural gain in function, on olfactory-specific deficits, ii) determine the TNS-enhanced effects of ST on olfactory-specific deficits, and iii) determine if TNS-enhanced ST, compared to ST, is also more efficacious in the treatment of other symptoms of Long COVID.
Conclusion
Post COVID persistent smell dysfunction and related deficits are relatively common with very few treatment options. Our proposed study will lay the groundwork for further development of ST and TNS as evidence-based treatments for Long COVID.
{"title":"Study of Chemosensory Enhancement through Neuromodulation Training (SCENT): Design and methodology of a randomized clinical trial for COVID-related persistent smell dysfunction","authors":"Nicole Cash , Mary Clare Koebel , Bashar W. Badran , Aicko Y. Schumann , Lisa M. McTeague , Thomas W. Uhde , Rodney J. Schlosser , Bernadette M. Cortese","doi":"10.1016/j.conctc.2025.101582","DOIUrl":"10.1016/j.conctc.2025.101582","url":null,"abstract":"<div><h3>Background</h3><div>Few evidence-based treatments exist for COVID-related persistent smell dysfunction. While smell/olfactory training (ST) has emerged as a widely prescribed, first line treatment, rigorous study is required to determine its efficacy in Long COVID. Additional study and development of adjunctive methods to improve the efficacy of ST is also needed.</div></div><div><h3>Methods</h3><div>This paper details the study design and methodology for a large, at-home, randomized, controlled trial designed to determine whether ST and/or trigeminal nerve stimulation (TNS)-enhanced ST improves Long COVID-related disturbances in smell function, mood, sleep, and cognition. Adults with COVID-related persistent smell dysfunction (N = 180) will be recruited and randomized to self-administer ST, placebo smell training (PBO), or TNS-enhanced ST daily for 12 weeks. Our primary objectives are to i) determine the efficacy of ST, compared to any natural gain in function, on olfactory-specific deficits, ii) determine the TNS-enhanced effects of ST on olfactory-specific deficits, and iii) determine if TNS-enhanced ST, compared to ST, is also more efficacious in the treatment of other symptoms of Long COVID.</div></div><div><h3>Conclusion</h3><div>Post COVID persistent smell dysfunction and related deficits are relatively common with very few treatment options. Our proposed study will lay the groundwork for further development of ST and TNS as evidence-based treatments for Long COVID.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101582"},"PeriodicalIF":1.4,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718958","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 : 2025-12-05DOI: 10.1016/j.conctc.2025.101584
Kathleen F. Pagulayan , Holly K. Rau , Rishika Das , Jennifer K. Bambara , Jeanne M. Hoffman , Rhonda M. Williams
Background and objectives
Veterans with a history of mild traumatic brain injury (mTBI) often report persistent post-concussive symptoms (PPCS). Clinical care guidelines recommend psychoeducation as well as assessment and treatment of the prevalent comorbid psychiatric, sleep, and pain conditions known to contribute to and amplify PPCS. The purpose of this site-randomized pragmatic trial is to examine the effectiveness of a novel 5-week cognitive rehabilitation/self-management intervention designed to increase engagement in treatment of comorbid conditions following mTBI evaluation in Veterans with cognitive PPCS.
Methods
On-TRACC (Tools for Rehabilitation and Cognitive Care), a 5-session manualized intervention, will be clinically rolled out at two Veterans Health Administration (VHA) Polytrauma sites, in randomized order, approximately a year apart. Veterans who complete a Comprehensive Traumatic Brain Injury Evaluation (CTBIE) after the clinical roll-out will be offered On-TRACC if deemed clinically appropriate by CTBIE clinical providers. Data collected from retrospective review of electronic health records (EHR) will be used to evaluate treatment engagement patterns for one year after CTBIE or one year after completion of On-TRACC for those who engage in the intervention. Participants receiving the On-TRACC intervention (n = 75) will be compared to those who complete the CTBIE but do not receive On-TRACC (n = 75). To evaluate clinical effectiveness and minimize sampling bias, no data will be gathered from participants directly.
Projected outcomes
The primary aim is to examine whether On-TRACC participation improves engagement in treatment of secondary conditions recommended by the CTBIE provider.
{"title":"The clinical rollout of a novel intervention for Veterans with persistent post-concussive symptoms: Protocol for a pragmatic 2-site trial of On-TRACC","authors":"Kathleen F. Pagulayan , Holly K. Rau , Rishika Das , Jennifer K. Bambara , Jeanne M. Hoffman , Rhonda M. Williams","doi":"10.1016/j.conctc.2025.101584","DOIUrl":"10.1016/j.conctc.2025.101584","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Veterans with a history of mild traumatic brain injury (mTBI) often report persistent post-concussive symptoms (PPCS). Clinical care guidelines recommend psychoeducation as well as assessment and treatment of the prevalent comorbid psychiatric, sleep, and pain conditions known to contribute to and amplify PPCS. The purpose of this site-randomized pragmatic trial is to examine the effectiveness of a novel 5-week cognitive rehabilitation/self-management intervention designed to increase engagement in treatment of comorbid conditions following mTBI evaluation in Veterans with cognitive PPCS.</div></div><div><h3>Methods</h3><div>On-TRACC (Tools for Rehabilitation and Cognitive Care), a 5-session manualized intervention, will be clinically rolled out at two Veterans Health Administration (VHA) Polytrauma sites, in randomized order, approximately a year apart. Veterans who complete a Comprehensive Traumatic Brain Injury Evaluation (CTBIE) after the clinical roll-out will be offered On-TRACC if deemed clinically appropriate by CTBIE clinical providers. Data collected from retrospective review of electronic health records (EHR) will be used to evaluate treatment engagement patterns for one year after CTBIE or one year after completion of On-TRACC for those who engage in the intervention. Participants receiving the On-TRACC intervention (n = 75) will be compared to those who complete the CTBIE but do not receive On-TRACC (n = 75). To evaluate clinical effectiveness and minimize sampling bias, no data will be gathered from participants directly.</div></div><div><h3>Projected outcomes</h3><div>The primary aim is to examine whether On-TRACC participation improves engagement in treatment of secondary conditions recommended by the CTBIE provider.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101584"},"PeriodicalIF":1.4,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718959","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 : 2025-12-05DOI: 10.1016/j.conctc.2025.101583
Isabel Stolz , Leonard Braunsmann , Franca Rosiny , Dieter Poehlau , Thomas Abel , Volker Anneken , Marion Drache , Kristel Knaepen
Background
Exercise and physical therapy have been shown to be effective in the non-pharmacological symptomatic treatment of multiple sclerosis (MS). Hippotherapy as an additive physical therapy intervention is applied in this study to promote balance and postural control, since the number of sufficiently high-quality randomized controlled trials indicating its effectiveness is limited.
Objective
This study aims to provide more in-depth insights into the effectiveness of hippotherapy in MS in terms of balance and other patient-relevant outcomes, building on the results of a preliminary study (MS-HIPPO II, evidence level 1b).
Methods
Based on a prospective, randomized, investigator-blinded, controlled multicenter study design, the primary endpoint of differences in balance will be investigated. Patients will be randomized to an intervention group (12 weeks of hippotherapy) or a control group (12 weeks of treatment as usual). Balance will be measured using the Berg Balance Scale (BBS) plus a standardized balance task on a force plate (AccuGait-Optimized, Advanced Mechanical Technology, Inc., Massachusetts, US) and a balance perturbation task on an oscillating sensorimotor therapy device (Bioswing Posturomed®, Haider, Pullenreuth, Germany). During balance tasks, electrocortical activity will be investigated using electroencephalography (EEG) (LiveAmp 32, Brain Products GmbH, Gilching, Germany). Secondary endpoints include fatigue (FSS), quality of life (MSQoL-54), pain (VAS), spasticity (NRS) and participation (WHODAS 2.0). Therapy progress will be documented via an ICF-based hippotherapy assessment-tool (EQUITEDO®, Frechen, Germany).
Results and conclusions
The results should contribute to improve the understanding of non-pharmaceutical treatment options in the field of exercise and movement therapy in MS.
Trial registration
The trial was registered at March 05, 2024 in the German Clinical Trial Register under DRKS00033449.
{"title":"Effectiveness of hippotherapy on balance performance, neurophysiological parameters and clinical symptoms of multiple sclerosis: Study protocol of a randomized controlled multicenter study (MS-HIPPO II - Movement in Balance)","authors":"Isabel Stolz , Leonard Braunsmann , Franca Rosiny , Dieter Poehlau , Thomas Abel , Volker Anneken , Marion Drache , Kristel Knaepen","doi":"10.1016/j.conctc.2025.101583","DOIUrl":"10.1016/j.conctc.2025.101583","url":null,"abstract":"<div><h3>Background</h3><div>Exercise and physical therapy have been shown to be effective in the non-pharmacological symptomatic treatment of multiple sclerosis (MS). Hippotherapy as an additive physical therapy intervention is applied in this study to promote balance and postural control, since the number of sufficiently high-quality randomized controlled trials indicating its effectiveness is limited.</div></div><div><h3>Objective</h3><div>This study aims to provide more in-depth insights into the effectiveness of hippotherapy in MS in terms of balance and other patient-relevant outcomes, building on the results of a preliminary study (MS-HIPPO II, evidence level 1b).</div></div><div><h3>Methods</h3><div>Based on a prospective, randomized, investigator-blinded, controlled multicenter study design, the primary endpoint of differences in balance will be investigated. Patients will be randomized to an intervention group (12 weeks of hippotherapy) or a control group (12 weeks of treatment as usual). Balance will be measured using the Berg Balance Scale (BBS) plus a standardized balance task on a force plate (AccuGait-Optimized, Advanced Mechanical Technology, Inc., Massachusetts, US) and a balance perturbation task on an oscillating sensorimotor therapy device (Bioswing Posturomed®, Haider, Pullenreuth, Germany). During balance tasks, electrocortical activity will be investigated using electroencephalography (EEG) (LiveAmp 32, Brain Products GmbH, Gilching, Germany). Secondary endpoints include fatigue (FSS), quality of life (MSQoL-54), pain (VAS), spasticity (NRS) and participation (WHODAS 2.0). Therapy progress will be documented via an ICF-based hippotherapy assessment-tool (EQUITEDO®, Frechen, Germany).</div></div><div><h3>Results and conclusions</h3><div>The results should contribute to improve the understanding of non-pharmaceutical treatment options in the field of exercise and movement therapy in MS.</div></div><div><h3>Trial registration</h3><div>The trial was registered at March 05, 2024 in the German Clinical Trial Register under DRKS00033449.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"49 ","pages":"Article 101583"},"PeriodicalIF":1.4,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926664","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 : 2025-12-01DOI: 10.1016/j.conctc.2025.101577
Samantha E. Daruwala , Kayley Stratton , Grace Y. Cho , Michael D. Anestis , Craig J. Bryan , Nicholas P. Allan
Background
In the United States (US), the proportion of firearm suicide deaths are higher among military personnel compared to the general population. Secure firearm storage practices (e.g., gun safe, unloaded) can reduce the risk of firearm suicide. A randomized controlled trial, called Project Safe Guard (PSG) found that providing lethal means counseling (LMC) to firearm-owning service members increased secure firearm storage practices; however, some still stored at least one firearm unsecurely. Intolerance of uncertainty (IU) may be a barrier to secure firearm storage that decreases the effectiveness of LMC. This study will examine the impact of a brief intervention that targets IU (i.e., Cognitive behavioral therapy for Uncertainty Enhanced; CUE) on improving the effectiveness of PSG-LMC on secure firearm storage practices among firearm-owning service members. In this protocol paper, we describe the rationale and methodology for this study.
Methods
This study uses a counterbalanced design with two conditions to test the acceptability, feasibility, and potential efficacy of both interventions with 100 current or recently discharged service members who report elevated IU and storing at least one firearm unsecurely. Participants are randomized to either receive CUE or PSG-LMC first, and then receive the second intervention approximately two weeks later. Participants will complete a baseline assessment, ecological momentary assessment (EMA) via their mobile devices, and follow-ups at 1-, 3-, 6-, 9-, and 12-months post-baseline. All interventions will be delivered remotely.
Conclusions
This study aims to inform how to improve firearm safety in military personnel with elevated IU.
{"title":"Study design and protocol for a randomized clinical trial investigating a brief fear of uncertainty-focused intervention as an adjunct to project safe guard for military personnel","authors":"Samantha E. Daruwala , Kayley Stratton , Grace Y. Cho , Michael D. Anestis , Craig J. Bryan , Nicholas P. Allan","doi":"10.1016/j.conctc.2025.101577","DOIUrl":"10.1016/j.conctc.2025.101577","url":null,"abstract":"<div><h3>Background</h3><div>In the United States (US), the proportion of firearm suicide deaths are higher among military personnel compared to the general population. Secure firearm storage practices (e.g., gun safe, unloaded) can reduce the risk of firearm suicide. A randomized controlled trial, called Project Safe Guard (PSG) found that providing lethal means counseling (LMC) to firearm-owning service members increased secure firearm storage practices; however, some still stored at least one firearm unsecurely. Intolerance of uncertainty (IU) may be a barrier to secure firearm storage that decreases the effectiveness of LMC. This study will examine the impact of a brief intervention that targets IU (i.e., Cognitive behavioral therapy for Uncertainty Enhanced; CUE) on improving the effectiveness of PSG-LMC on secure firearm storage practices among firearm-owning service members. In this protocol paper, we describe the rationale and methodology for this study.</div></div><div><h3>Methods</h3><div>This study uses a counterbalanced design with two conditions to test the acceptability, feasibility, and potential efficacy of both interventions with 100 current or recently discharged service members who report elevated IU and storing at least one firearm unsecurely. Participants are randomized to either receive CUE or PSG-LMC first, and then receive the second intervention approximately two weeks later. Participants will complete a baseline assessment, ecological momentary assessment (EMA) via their mobile devices, and follow-ups at 1-, 3-, 6-, 9-, and 12-months post-baseline. All interventions will be delivered remotely.</div></div><div><h3>Conclusions</h3><div>This study aims to inform how to improve firearm safety in military personnel with elevated IU.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"48 ","pages":"Article 101577"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623719","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 : 2025-12-01DOI: 10.1016/j.conctc.2025.101579
Junhong Su , Bettina E. Hansen , Zifang Wang , Abylaikhan Sharmenov , Xueshan Xia , Michelle Broekhuizen , Zhongren Ma , Maikel P. Peppelenbosch
Background
Although the gut microbiome plays a crucial role for maintaining overall host homeostasis and metabolism, it is significantly influenced by dietary changes, leading to substantial temporal variations in microbial composition within and between individuals. Despite this, incidental fecal sampling remains the standard method for microbiome assessment. Recently, the blood microbiome, defined by microbial DNA (cmDNA) circulating in the bloodstream, has emerged as a potentially more stable and integrated alternative. Preliminary data suggest that blood microbiome analysis may offer more consistent insights than fecal-based approaches, although the methodological validity of the approach has been questioned.
Method/design
This study aims to establish or rule-out cmDNA as a representative of the gut microbiome. In a prospective, single-arm crossover trial, effects of dairy product withdrawal and reintroduction of a yoghurt with a known consortium of bacteria will be assessed in healthy volunteers aged 18–65. Participants will first abstain from all dairy products, a phase expected to reduce yogurt-associated cmDNA in the bloodstream. Yogurt will then be reintroduced, during which reappearance of cmDNA of specific bacteria (especially LGG, LA-5 and BB-12) is anticipated. Shotgun metagenomic sequencing will be used to track cmDNA dynamics over time. This longitudinal sampling approach will provide experimental evidence supporting the existence and responsiveness of the circulating microbiome, while also revalidating the bioinformatic pipeline used for its analysis.
Conclusion
This pilot study will test whether blood-derived microbial DNA can serve as a valid surrogate for gut microbiome composition. If successful, this approach may provide a more stable and integrative alternative to fecal sampling and support future biomarker development and mechanistic research.
{"title":"Yogurt reintroduction and the circulating microbiome in healthy volunteers: protocol for a prospective, longitudinal, species-controlled crossover clinical trial (MAMI)","authors":"Junhong Su , Bettina E. Hansen , Zifang Wang , Abylaikhan Sharmenov , Xueshan Xia , Michelle Broekhuizen , Zhongren Ma , Maikel P. Peppelenbosch","doi":"10.1016/j.conctc.2025.101579","DOIUrl":"10.1016/j.conctc.2025.101579","url":null,"abstract":"<div><h3>Background</h3><div>Although the gut microbiome plays a crucial role for maintaining overall host homeostasis and metabolism, it is significantly influenced by dietary changes, leading to substantial temporal variations in microbial composition within and between individuals. Despite this, incidental fecal sampling remains the standard method for microbiome assessment. Recently, the blood microbiome, defined by microbial DNA (cmDNA) circulating in the bloodstream, has emerged as a potentially more stable and integrated alternative. Preliminary data suggest that blood microbiome analysis may offer more consistent insights than fecal-based approaches, although the methodological validity of the approach has been questioned.</div></div><div><h3>Method/design</h3><div>This study aims to establish or rule-out cmDNA as a representative of the gut microbiome. In a prospective, single-arm crossover trial, effects of dairy product withdrawal and reintroduction of a yoghurt with a known consortium of bacteria will be assessed in healthy volunteers aged 18–65. Participants will first abstain from all dairy products, a phase expected to reduce yogurt-associated cmDNA in the bloodstream. Yogurt will then be reintroduced, during which reappearance of cmDNA of specific bacteria (especially LGG, LA-5 and BB-12) is anticipated. Shotgun metagenomic sequencing will be used to track cmDNA dynamics over time. This longitudinal sampling approach will provide experimental evidence supporting the existence and responsiveness of the circulating microbiome, while also revalidating the bioinformatic pipeline used for its analysis.</div></div><div><h3>Conclusion</h3><div>This pilot study will test whether blood-derived microbial DNA can serve as a valid surrogate for gut microbiome composition. If successful, this approach may provide a more stable and integrative alternative to fecal sampling and support future biomarker development and mechanistic research.</div></div><div><h3>Clinical trial registration</h3><div>NCT06944002.</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"48 ","pages":"Article 101579"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623835","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 : 2025-12-01DOI: 10.1016/j.conctc.2025.101571
Selenia Rubio , Patricia Cabrera , Rory Reever , Cesar Migliorati , Richard Ohrbach , Frank C. Gibson III , Zhigang Li , Angela Mickle , Rosalynn R.Z. Conic , Roger B. Fillingim , Margarete Ribeiro Dasilva
Evidence-based treatments for painful temporomandibular disorders (TMD) are lacking. The most common treatments for painful TMDs, intraoral appliances and pain medication, provide suboptimal pain control, often leading to treatment-limiting adverse effects. Photobiomodulation therapy (PBM) shows substantial potential for the management of pain in people with a TMD; however, its efficacy for TMD pain reduction has not been rigorously tested. We will conduct a double-blind, randomized, placebo-controlled clinical trial of multimodal PBM for TMD pain. This single-site trial will randomize 130 participants, aged 18 years and older, with chronic painful TMD. Individuals will complete a detailed medical history to confirm eligibility criteria, followed by a clinical exam to confirm TMD case status according to the Diagnostic Criteria for TMD (DC/TMD). Eligible participants will be randomized to either active or sham PBM treatment. Participants will complete eight treatment visits scheduled 2–5 days apart. This will be followed by a post-intervention visit that will include symptom questionnaires, TMD exam, pressure pain threshold (PPT) measures, and blood draw. A 6-month follow-up visit will include a TMD exam, questionnaires, and pressure pain threshold measures. Analyses will determine intervention effects on the primary outcome (pain intensity) and multiple secondary outcomes and will examine whether changes in inflammation and pain sensitivity are associated with the intervention response.
{"title":"A protocol for a randomized controlled trial of photobiomodulation for management of temporomandibular disorder pain in Adults","authors":"Selenia Rubio , Patricia Cabrera , Rory Reever , Cesar Migliorati , Richard Ohrbach , Frank C. Gibson III , Zhigang Li , Angela Mickle , Rosalynn R.Z. Conic , Roger B. Fillingim , Margarete Ribeiro Dasilva","doi":"10.1016/j.conctc.2025.101571","DOIUrl":"10.1016/j.conctc.2025.101571","url":null,"abstract":"<div><div>Evidence-based treatments for painful temporomandibular disorders (TMD) are lacking. The most common treatments for painful TMDs, intraoral appliances and pain medication, provide suboptimal pain control, often leading to treatment-limiting adverse effects. Photobiomodulation therapy (PBM) shows substantial potential for the management of pain in people with a TMD; however, its efficacy for TMD pain reduction has not been rigorously tested. We will conduct a double-blind, randomized, placebo-controlled clinical trial of multimodal PBM for TMD pain. This single-site trial will randomize 130 participants, aged 18 years and older, with chronic painful TMD. Individuals will complete a detailed medical history to confirm eligibility criteria, followed by a clinical exam to confirm TMD case status according to the Diagnostic Criteria for TMD (DC/TMD). Eligible participants will be randomized to either active or sham PBM treatment. Participants will complete eight treatment visits scheduled 2–5 days apart. This will be followed by a post-intervention visit that will include symptom questionnaires, TMD exam, pressure pain threshold (PPT) measures, and blood draw. A 6-month follow-up visit will include a TMD exam, questionnaires, and pressure pain threshold measures. Analyses will determine intervention effects on the primary outcome (pain intensity) and multiple secondary outcomes and will examine whether changes in inflammation and pain sensitivity are associated with the intervention response.</div></div><div><h3>Clinicaltrials.gov identifier</h3><div>NCT05916235</div></div>","PeriodicalId":37937,"journal":{"name":"Contemporary Clinical Trials Communications","volume":"48 ","pages":"Article 101571"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623717","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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