Trials最新文献

Traditional randomised controlled trials (RCTs) have long been considered the gold standard for evaluating clinical interventions. However, registry-based trials (RBTs) are emerging as a promising methodology, offering the potential for generating high-quality clinical evidence with greater external validity, reduced complexity, and lower costs. Despite being hailed as the "next disruptive technology in clinical research", the adoption of RBTs has been slower than anticipated. This lag could be attributed, in part, to the lack of consistent definitions for RBTs, which are often conflated with registry-based RCTs (RRCTs). Our analysis of seven RRCT reviews revealed significant variability in how RRCTs are defined and reported across clinical trial registries, reflecting the absence of standardised descriptors and nomenclature when registering these trials on clinical trial registries. This ambiguity complicates accurate estimation of their implementation and impact, reflected in reviews reporting widely varying numbers of trials registered as RRCTs. While RRCTs represent a valuable approach for addressing critical research questions, for their full potential to be realised, clear and consistent definitions, along with consensus on standardised registration terms, are essential. Given this, we would propose a taxonomy for RRCTs based on how the registry is used to support a RCT. We also welcome the CONSORT extension for the reporting of RRCTs and advocate for a standardised approach on how they are registered on clinical trial registries. Achieving this would not only enhance the recognition of RRCTs but also their impact on clinical practice. We propose a two-tier RRCT classification based on the number of outcomes captured in the registry and its use for identification or recruitment of participants, and encourage ongoing discussion around RRCT taxonomy to help guide future research.

Background: Among the general public, the ketogenic (KETO) diet is popular for weight loss and may also support glycemic control in people with type 2 diabetes (T2D). Obesity and T2D have both been associated with diminished immune responses, increasing the risk of infection. KETO diets are often high in saturated fats (SFA), which may increase cardiovascular disease (CVD) risk as well as inflammation. Substituting SFA for unsaturated fats (UFA) may improve these outcomes. This study aims to compare lipid measures, glycemia, inflammation, and immune function in people with, or at risk of developing, T2D after following KETO diets emphasizing SFA versus UFA versus a low-fat standard of care diet (LFD) for 6 months. We hypothesize that (1) circulating triglycerides (TG) will be reduced more in the two KETO groups relative to the control LFD and (2) low-density lipoprotein (LDL-C) will be lowered to a greater extent with higher UFA consumption relative to KETO rich in SFA.

Methods: The KETO-IM study is an open-label, single-center, three parallel-arm, superiority, randomized controlled trial (RCT). It will enroll adults aged 18 to 70 years with body mass index (BMI) > 23 kg/m² (Asian and South Asian), or > 25 kg/m² (non-Asian) and glycated hemoglobin (HbA1c) > 5.7%, recruited by the study team from the community in Edmonton, Canada and surrounding area. Participants (175 total) will be allocated to three groups in a 1:1:1 ratio with evaluation endpoints at three and six months compared to baseline. The primary outcomes assessing CVD risk, will be plasma LDL-C and TG. Secondary outcomes of the trial include glucose metabolism, inflammation and immune function. Among the secondary outcomes, comparison of immune function will be a novel focus.

Discussion: This trial will directly compare the effects of fat sources in a KETO diet to a control LFD on cardiometabolic risk, inflammation and immune function in adults of both sexes. The results of this trial can be used to guide clinical advice to patients seeking to improve lipid and glycemic control while, for the first time, comparing the effects of KETO diets on immune response.

Trial registration: ClinicalTrials.gov, NCT05681468. Registered on 12 December 2022, https://clinicaltrials.gov/study/NCT05681468?titles=keto-im&rank=1. First enrollment September 18, 2023.

Background: There is an urgent need for interventions which reduce dementia risk in aging adults. People with subjective cognitive decline (SCD) have a greater risk of developing dementia compared to age-matched cognitively normal individuals. Impaired cerebral blood flow (CBF) and cerebral glucose hypometabolism are leading mechanisms underlying dementia that could be ideal interventional targets for this population. Recent research, including our own work, has shown that oral consumption of ketone monoesters (KME) can improve CBF and cerebral metabolism, which in turn can improve cognition. The purpose of this study is to investigate the hypothesis that a 14-day KME supplementation intervention in middle-to-older adults with SCD will increase CBF, brain functional connectivity, and cognitive performance in comparison to placebo.

Methods: A total of 34 middle-to-older adults (50% female, aged 55-75) with SCD will be recruited for this randomized placebo-controlled crossover double-blind trial. Participants will complete study visits immediately before and after 14 days of thrice-daily supplementation with a KME or a placebo. Following a minimum 14-day washout period, participants will repeat the protocol to complete study visits immediately before and after 14 days of thrice-daily supplementation with the other intervention (KME or placebo). The outcome measures are as follows: (1) CBF, functional brain connectivity, and cerebrovascular function as measured by brain magnetic resonance imaging (MRI) scans, (2) cognitive function assessed via a battery of validated psychometric tests, and (3) blood-borne neurotrophic factors via venous blood sample collection.

Discussion: This novel study aims to advance our understanding of how KME could be an effective intervention to combat dementia risk factors and improve aspects of brain health in middle-to-older adults with SCD.

Trial registration: ClinicalTrials.gov NCT06588946. Registered on 05 September 2024.

Background: People with mild cognitive impairment (MCI) fall as often as people living with early dementia. Yet, few trials have investigated the effectiveness of fall prevention interventions for people with MCI. Recruitment of specific populations into long-term trials can be challenging, and to assist future studies, it is necessary to better understand more about trial recruitment. This study outlines the recruitment of people with MCI into the Balance on the Brain trial. This was a single-blind randomised controlled trial based in the Perth Metropolitan Area, which included people living with MCI in the community, aged 50 or over, and who were self-reported to not be meeting the Australian physical activity guidelines. The multi-modal exercise intervention was for 6 months, and all participants were followed up monthly for 12 months. A sample size of 396 was calculated to meet the requirements for the falls primary outcome (212 participants for the balance primary outcome).

Methods: Eleven recruitment strategies were used across the 36-month recruitment (January 2021 through to December 2023). Some recruitment strategies had costs, and these are also outlined.

Results: A total of 780 potential participants were initially prescreened, 258 completed full REDCap^® screening, and 128 people were recruited. Memory clinics/hospitals were the most successful recruitment source, followed by Facebook advertisements and radio.

Discussion: Recruiting people with MCI can be difficult, exacerbated in this study by the concurrent COVID-19 pandemic. Less restrictive inclusion criteria and multisite recruitment may provide greater success.

Trials registration: Australian New Zealand Clinical Trials Registry (ANZCTRN) ACTRN12620001037998. Registered on 12 October 2020.

Background: The anti-inflammatory diet exerts its effects by suppressing inflammatory mediators and modulating gut microbiota to reduce inflammation. However, its safety and efficacy in early nutritional management for patients with mild pancreatitis remain to be evaluated.

Objective: This study aims to evaluate both the efficacy and safety of an early introduction of an anti-inflammatory diet in patients with mild acute pancreatitis.

Methods: This single-center randomized controlled trial enrolled 72 patients with mild acute pancreatitis (revised Atlanta criteria), randomly assigning 36 patients to each group. The intervention group received an early oral anti-inflammatory diet protocol featuring: ① oral intake initiation within 48 h; ② the daily food intake followed a diet with a Dietary Inflammatory Index (DII) score of less than 0, as formulated by the research group. The control group received conventional management: physician-directed oral intake initiation and a stepwise advancement from "clear liquid to full liquid to low-fat soft diet." Primary outcomes included inflammatory biomarkers, nutritional indicators, and gut microbiota (16S rRNA sequencing). Secondary outcomes were average hospital stay and costs.

Discussion: The positive findings of this study may offer novel clinical practice guidelines for early nutritional support in patients with mild acute pancreatitis. However, as a single-center study, further validation through multi-center studies with larger sample sizes is still required.

Trial registration: Chinese Clinical Trial Registry ChiCTR2400094056. https://www.chictr.org.cn/index.html.

Background: Venous thromboembolism (VTE) is a common and potentially fatal complication in orthopedic trauma patients, particularly following lower limb and hip-related fractures. While pharmacological prophylaxis is the cornerstone of prevention for patients at moderate to high risk, its use is a balance between efficacy and bleeding risk. Clinical pharmacists play an increasingly important role in optimizing pharmacotherapy, but evidence for the effectiveness of a comprehensive, pharmacist-led management model spanning both inpatient and outpatient care for VTE prophylaxis in this population is scarce.

Methods: This is a single-center, prospective, randomized controlled trial. One hundred seventy eligible orthopedic trauma patients at risk for VTE will be randomly allocated in a 1:1 ratio to either the intervention group or the control group. The intervention group will receive a pharmacist-led, full-course management model, which includes personalized VTE risk (Caprini score) and bleeding risk assessment, medication reconciliation, patient education, dosing optimization, adverse event monitoring, and structured follow-up via telephone at 21, 35, and 90 days post-discharge. The control group will receive standard medical care without this structured pharmacist intervention. The primary outcome is the incidence of symptomatic and asymptomatic VTE within 90 days post-surgery. Secondary outcomes include the incidence of major and clinically relevant non-major bleeding events, medication adherence (measured by Medication Possession Ratio). Data will be analyzed on an intention-to-treat basis.

Discussion: This randomized controlled trial aims to generate high-quality evidence on the effectiveness of a clinical pharmacist-led management model for improving outcomes in orthopedic trauma patients requiring VTE prophylaxis.

Trial registration: The study has been registered in the Chinese Clinical Trial Registry (retrospectively registered no. ChiCTR2500107932) on 21 August 2025, at https://www.chictr.org.cn/showproj?proj=279391.

Background: Stroke remains a leading cause of long-term disability worldwide, with a significant proportion of survivors suffering from persistent upper limb impairments despite conventional rehabilitation. High-definition transcranial direct current stimulation (HD-tDCS) has emerged as a promising neuromodulation technique capable of precise cortical targeting, potentially enhancing motor recovery when combined with structured rehabilitation. This study aims to confirm the efficacy and safety of HD-tDCS combined with digital upper limb rehabilitation in improving upper limb motor function among stroke survivors.

Methods: This multicenter, randomized, parallel-group, double-blind, sham-controlled superiority trial will enroll 64 participants with chronic unilateral stroke who will be randomized to receive either active HD-tDCS or sham stimulation, both combined with standardized digital upper limb rehabilitation. The intervention will consist of 10 sessions over 4 weeks (40 min per session). Each session will include 10 min of HD-tDCS at rest targeting the ipsilesional primary motor cortex and anterior intraparietal sulcus, followed by 20 min of task-based digital rehabilitation with concurrent HD-tDCS, and a final 10 min of digital rehabilitation alone. The primary outcome will be the postintervention change in the Fugl-Meyer Assessment of Upper Extremity score from baseline. Secondary outcomes will include grip and pinch strength, 9-Hole Pegboard Test, Box and Block Test, finger-tapping performance, Short Form-36, and cortical activation measured via integrated functional near-infrared spectroscopy (fNIRS). fNIRS will help characterize task-related cortical hemodynamic responses in the stimulated area, which are associated with motor recovery.

Discussion: This trial provides promising exploratory findings and is designed to rigorously assess both behavioral and hemodynamic brain responses. By integrating real-time brain monitoring, this study seeks to contribute to existing evidence on the mechanisms underlying HD-tDCS-enhanced neuroplasticity and inform the development of future precision neurorehabilitation strategies.

Trial registration: This trial has been registered at the Clinical Research Information Service (Registration number: KCT0010556). Registration date: May 28, 2025.

Background: Spinal pain is a highly prevalent condition affecting a large part of the population. Chiropractic maintenance care (MC) is a management strategy intended to prevent spinal pain recurrent episodes and deterioration by treating patients at pre-planned intervals. A previous study showed that patients identified as a dysfunctional subgroup by the West Haven-Yale Multidimensional Pain Inventory (MPI) and receiving MC had fewer days with bothersome LBP. This suggests MC may have superior effectiveness in this subgroup of patients. The MPI, however, is not practical for daily clinical practice, prompting the development of the MAINTAIN instrument. This study aims to (1) assess the effectiveness and cost-effectiveness of stratified MC using the MAINTAIN instrument, and (2) assess the fidelity and procedure compliance of implementing the MAINTAIN instrument.

Methods: This pragmatic randomized clinical trial will recruit 225 consecutive patients (18-65 years old) with significant (> 30 days in the past 12 months) recurrent spinal pain presenting to chiropractic clinics. After the initial 3 weeks (6 visits) of chiropractic care, patients will be randomized to receive either Stratified MC or Standard Chiropractic Care. Stratified MC: patients will complete the MAINTAIN instrument and be stratified to MC or symptom-guided care (clinicians' judgment). Patients in the Standard Chiropractic Care arm will receive standard treatment based on the chiropractor's judgment. The primary outcome is the total number of days with activity-limiting pain measured at 12 months. Secondary outcomes include the number of missed working days and loss of work productivity due to pain, pain intensity, disability, health-related quality of life, perceived improvement, and implementation of MAINTAIN instrument outcomes. An intention-to-treat protocol and generalized estimating equations (GEE) linear regression models will be used for analysis.

Discussion: This study investigates the impact of using a clinical instrument to identify patients with recurrent spinal pain to target those who benefit most from a chiropractic MC approach. Strict inclusion criteria should ensure a suitable target group, and frequently collected repeated measures should provide accurate outcome assessment. The study is pragmatic and includes standard clinical procedures facilitating the generalizability and transferability of the results into clinical practice.

Trial registration: ClinicalTrials.gov NCT05350254. Prospectively registered on April 22, 2022, last modified on December 08, 2023. The first patient was randomized into the study on December 21, 2023.

Background: Outpatient surgery means that the patient patient has surgery and often goes home on the same day. Safety and utilization outcomes were similar between outpatient and inpatient bariatric surgeries, and outpatients were associated with shorter hospital readmission lengths of stay. At the same time, it is necessary to evaluate how the possibility of accommodating an operated patient, for example, in an apartment integrated with the Ambulatory Surgical Center (ASC), will allow for discharge on the same day or one day after surgery. The researchers suggest that the differences in the "increased length of stay" criterion between the "same-day" (outpatients) and "one-day" (inpatients) groups after the procedure are minor. The safety and readmission rates of outpatients and inpatients who underwent laparoscopic gastric bypass using FundoRing were comparable. The objective of this study was to first aim to assess the cases of the extra length of stay of the pre-planned discharge date and the difference and reason between the "fit for discharge" and "actual discharge" dates. The second aim was to assess the safety and readmission of outpatient same-day and one-day laparoscopic one anastomosis gastric bypass by using the "FundoRing" method with an enhanced recovery protocol and remote monitoring in the ambulatory surgery center with integrated apartments.

Methods: The study design was a single-center prospective, interventional, open-label (no masking) RCT with 1-year follow-up. Adult obese patients (n = 200) were randomly allocated to one of two groups. Experimental surgical bariatric group: first (A) group: patients (n = 100) (Same-DayFundoRingOAGB group); active comparator surgical bariatric group; second (B) group: patients (n = 100) (One-DayFundoRingOAGB group). The Same-DayFundoRingOAGB group was assessed as outpatients and the One-DayFundoRingOAGB group as inpatients.

Discussion: The study participants were divided into two groups based on their discharge date. This study identified subjective and objective factors influencing discharge timing. It will answer the question: How can the difference between the "fit for discharge" and "actual discharge" dates be minimized? What interventions could have influenced this? An answer will also be given to the question: How can an apartment integrated with the ASC reduce the extra length of stay at the ASC?

Trial registration: ClinicalTrials.gov ID: NCT07189416. The Same-Day trial was retrospectively registered on 09.22.2025.

Background: Chronic stress is detrimental to the maintenance of the main response system - the hypothalamic-pituitary-adrenal (HPA) axis. The current study aimed to investigate the efficacy of two plant-based adaptogens, a formula containing Rhodiola, holy basil and Schisandra chinensis (VL-G-A57) and a full-spectrum ashwagandha (VL-G-E12), on stress and related symptoms in individuals with high stress.

Materials and methods: The 60-day randomized, double-blind, placebo-controlled clinical study included individuals aged between 18 to 65 years with a body mass index (BMI) of 18 to 29.9 kg/m². One hundred eighty-six participants were randomized to one of the adaptogens, VL-G-A57 or VL-G-E12, or to placebo. The primary outcome was a reduction in stress levels. Secondary outcomes were changes in sleep quality, fatigue, restorative sleep, mental alertness, mood dysregulation, and anxiety. A priori power analysis determined the required sample size. Efficacy was assessed by comparing mean changes in the primary endpoint at days 30 and 60 using ANCOVA, with baseline values as covariates. Dunnett's post hoc test identified significant differences versus placebo, and within-group changes were evaluated using paired t-tests. Normality was assessed visually and via Shapiro-Wilk/Kolmogorov-Smirnov tests as needed. Secondary outcomes were analyzed similarly. Analyses were conducted using R (v4.0.5) and XLSTAT (v2021.3.1).

Results: At day 60, both VL-G-A57 and VL-G-E12 significantly reduced Perceived Stress Scale (PSS) scores compared to placebo (p < 0.0001). Sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), improved significantly in both adaptogen groups (VL-G-A57: p = 0.0008, VL-G-E12: p < 0.0001). This corresponded well with the Restorative Sleep Questionnaire-Weekly (RSQ-W) results in the two IP arms when compared with placebo (p < 0.0001). Additionally, mood dysregulation (VL-G-A57: p = 0.0454), anxiety (VL-G-A57: p = 0.0004, VL-G-E12: p = 0.0015), and stress levels (VL-G-A57-VL-G-E12: p < 0.0001) showed significant improvements compared to placebo. No differences in mental alertness were observed.

Conclusion: The study concluded that both VL-G-A57 and VL-G-E12 were associated with reductions in stress, fatigue, and anxiety while improving mood and sleep quality.

Trial registration: ClinicalTrials.gov NCT05602389 and the Clinical Trials Registry - India CTRI/2022/11/047635. Registered on 1 November 2022 and 24 November 2022.