Tag: Clinical trial

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Impact of Prescribed and Self-Selected Music Interventions on Stress, Sleep, Heart Rate Variability, and Brain Connectivity in Surgeons Using 7-Tesla Functional Magnetic Resonance Imaging and Wearable Actigraphy: Multimodal Feasibility Randomized Controlled Trial

<strong>Background:</strong> Stress, sleep deprivation, and burnout are significant safety risks for acute care surgeons, negatively impacting performance, well-being, and clinical outcomes. <strong>Objective:</strong> This pilot randomized controlled trial aimed to measure neurophysiological effects of prescribed music (PM) and self-selected music (SSM) on surgeon stress, burnout, and neurophysiological responses using a multimodal protocol that integrated functional magnetic resonance imaging (fMRI), wearable biosensor monitoring, and psychological self-assessments. <strong>Methods:</strong> Full-time attending surgeons at a quaternary care hospital were invited to participate in a 3-armed trial (1:1:1 block allocation). Intervention groups were instructed to listen to 30 minutes (minimum 15 minutes) of either PM or SSM daily at bedtime for 6 weeks, reflecting real-world conditions. PM comprised original compositions based on elements promoting perceived relaxation from a prior study. The control arm avoided music in the 30 minutes before bed. Allocation was concealed from the recruiting investigator; the fMRI technicians, the statistician, and lead investigators were blinded until analyses were completed. Functional connectivity patterns were measured using fMRI at baseline and 6 weeks while participants listened to simulated intensive care unit noise, PM, and SSM. Secondary outcomes included continuous actigraphy for sleep quality and self-reported anxiety, sleep quality, and burnout using validated scales (State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, and Maslach Burnout Inventory). <strong>Results:</strong> A total of 22 surgeons were assessed; demands of fMRI and data collection schedule led 3 to decline and 2 (allocated to PM) not to finish baseline measures; 6 PM, 5 SSM, and 6 controls received allocated intervention; 2 PM participants were withdrawn for nonadherence and missing follow-up data and 1 control missed follow-up collection due to scheduling (final analysis set after missing data: PM: n=4, SSM: n=5, control: n=5). One control participant experienced transient vertigo in fMRI. Trends in fMRI data indicated that both intervention groups experienced less negative emotional arousal and anxiety, with physical tension reduced in the PM group. The PM group exhibited reduced stress response in the frontal lobes when exposed to intensive care unit alarms, suggesting diminished attentional response to the high-stress auditory environment, compared to control. However, lack of statistical significance and baseline variability entail cautious interpretation. Observations of sleep quality were mixed, and no statistically significant differences in stress surveys were observed. <strong>Conclusions:</strong> Both music interventions trended toward positive changes in neurophysiological responses, suggesting potential benefits in reducing surgeon stress. However, due to the small sample, mixed or nonsignificant results, and the exploratory nature of this study, findings should be considered preliminary. Further research with larger, diverse cohorts is required to confirm trends, refine both the intervention approach and recruitment strategies, and determine whether objective compositional elements or personally selected music drive the mechanisms of potential positive effects. <strong>Trial Registration:</strong> ClinicalTrials.gov NCT05980429; https://clinicaltrials.gov/study/NCT05980429
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Immune Priming Could End Immunosuppression After Liver Transplant

Results from a Phase I/IIa trial show promise for an immune priming approach where donor immune cells are infused into liver transplant recipients before surgery. In the small-scale clinical trial, three patients were reported to remain completely off immunosuppression for over three years thanks to this treatment. 

Recipients of organ transplants need to take lifelong medication to prevent the immune system from rejecting the transplant. In the case of end-stage liver disease patients, the serious side effects of immunosuppressants are considered acceptable in the face of a severe and life-threatening condition. Still, researchers have long been looking for strategies to at least reduce the intensity and duration of this treatment, which would significantly improve the health of these patients and the financial burden of long-term immunosuppression. 

“Long-term use of immunosuppressive drugs can harm the kidneys, causes metabolic complications, makes patients more susceptible to infections and certain types of cancer, as well as diabetes,” said Angus Thomson, PhD, DSc, professor of surgery and immunology at the University of Pittsburgh’s School of Medicine (UPMC). “Sparing patients from these serious side effects has been a goal that Pittsburgh transplant scientists began pursuing three decades ago. It is an honor to achieve this important milestone toward finally realizing that dream.”

The immune priming approach developed by Thomson’s team makes use of regulatory dendritic cells (DCregs), a type of immune cell that regulate innate and adaptive immunity and have the ability to train the immune system to stop recognizing transplanted cells as foreign. The treatment is made by extracting monocytes from the donor’s blood and inducing them to turn into DCregs. 

Launched in 2017, the clinical trial recruited a total of 13 patients who were infused with DCregs from their donor a week before surgery. A year after surgery, transplant recipients underwent a biopsy and an assessment to determine if they were eligible for immunosuppressant withdrawal.

Out of eight patients who stopped taking immunosuppressants, four achieved complete withdrawal and three of them remained off immunosuppression therapy for over three years. These findings represent a significant improvement compared to the rate of patients who successfully withdraw from immunosuppression without intervention, raising it from 16% to 37%. 

“For as long as organ transplantation has been a field of medicine, tolerance has been its holy grail,” said Abhinav Humar, MD, clinical director of the Starzl Transplantation Institute and chief of the division of transplantation at UPMC. “While we haven’t hit a home run yet, we’ve definitely gotten on base by reliably and safely removing immunosuppression early after transplantation from a significant percentage of patients, which is a huge breakthrough.”

While preliminary efficacy results seem promising, the main objective of this small scale trial was to establish the treatment’s safety and feasibility. Based on these results, a larger scale, randomized trial will be designed and conducted with the purpose of establishing the efficacy of this immune priming approach. 

In future studies, the researchers also want to explore the use of an alternative immunosuppressant medication that may be more likely to allow DCregs to stop immune rejection against the transplant, as well as studying the effects of infusing the donor cells after surgery and looking for ways of obtaining these cells from deceased donors to expand the potential applications of this approach. 

“There are so many tantalizing paths we could take to help our findings benefit many more patients,” Thomson said. “We are very interested in collaborating with other transplantation centers to accelerate and scale our clinical research.”

The post Immune Priming Could End Immunosuppression After Liver Transplant appeared first on Inside Precision Medicine.

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Development of iGET Living, a Digital Graded Exposure Intervention for Youth With Chronic Pain: Multiphase User-Centered Design and Pilot Study

Background: Pediatric chronic pain affects up to one-third of youth and is associated with significant disruptions in social, emotional, and behavioral functioning. Although behavioral treatments are effective, access remains limited due to geographic, financial, and systemic barriers. Digital behavioral health interventions offer a promising solution, but many lack user-centered design, iterative refinement, and implementation-informed development strategies that support usability and scalability. Objective: This study aimed to develop and iteratively refine iGET Living, a digital graded exposure intervention for youth with chronic pain, using a combined user-centered and implementation-informed framework, and to evaluate its preliminary acceptability, feasibility, and user-perceived success. Methods: Guided by the Consolidated Framework for Implementation Research (CFIR) and the mHealth (mobile health) Agile Development and Lifecycle model, intervention development proceeded through 3 phases. Phase 0 translated an evidence-based in-person graded exposure treatment (GET Living) into an initial digital prototype. Phase 1 involved iterative user-centered refinement across 3 cycles of qualitative development sessions with youth with chronic pain (n=15), incorporating think-aloud usability testing, Likert-rated feedback, and rapid qualitative analysis mapped to CFIR constructs to guide real-time modifications to content, design, and functionality. Phase 2 piloted the refined intervention with a new sample of youth (n=38, n=30 completers) recruited from a tertiary pediatric pain clinic to evaluate feasibility, acceptability, treatment credibility and expectancy, and user-perceived functional improvements. Quantitative outcomes were summarized descriptively, and qualitative exit interview data were analyzed using rapid qualitative analysis. Results: Across development cycles, youth feedback informed substantive refinements to the intervention, including reducing text density, incorporating animated educational videos, enhancing interactive features, and improving navigation and layout. These changes resulted in progressive improvements in clarity, satisfaction, and acceptability across prototypes. In the Phase 2 pilot study, participants reported moderate-to-high treatment credibility (mean of 19.71 out of 30) and expectancy (mean of 17.96 out of 30), as well as high satisfaction (mean of 46.12 out of 60). Acceptability ratings across domains of the Theoretical Framework of Acceptability were favorable. Qualitative exit interviews highlighted the interventions’ perceived role in helping youth re-engage in valued activities. Conclusions: Using a combined CFIR and agile development approach, iGET Living emerged as a feasible, acceptable, engaging digital graded exposure intervention for youth with chronic pain. These findings highlight the value of integrating implementation frameworks and participatory design early in digital intervention development and support further evaluation in a preliminary efficacy trial. Trial Registration: ClinicalTrials.gov NCT05079984; https://clinicaltrials.gov/study/NCT05079984 International Registered Report Identifier (IRRID): RR2-10.1136/bmjopen-2022-065997
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Experiences From an Internet-Delivered Treatment Program for Individuals With Obesity: Pilot Study

Background: The prevalence of obesity is a global health challenge, as obesity is associated with various comorbidities, reduced quality of life, and increased mortality. Providing effective treatment to improve health and quality of life for people with obesity is a major health care concern. Internet-delivered treatment (IDT) is an alternative treatment that increases patient accessibility and reachability; however, pilot testing is required before such interventions are evaluated in full-scale studies or implemented. Objective: This study aims to investigate the feasibility and user-friendliness of an IDT program for obesity (IDT-O); to evaluate body weight, dietary habits, physical activity, psychosocial functioning, and experiences of treatment in those who completed the 6-month treatment; and to investigate the dropouts’ experiences of the treatment. Methods: A prospective 1-year observational approach, evaluated through a multimethod research design, was adopted. Inclusion criteria were age 18 years and older, BMI of ≥30 kg/m, or BMI of 28‐29.9 kg/m with obesity-related comorbidity. Participants were offered a 6-month therapist-assisted IDT-O program providing evidence-based obesity treatment, behavioral and lifestyle support, and strategies to address weight stigma. BMI, participants’ dietary habits, self-reported physical activity, psychosocial functioning, experiences of treatment effects, and treatment satisfaction were measured before treatment and after 6 and 12 months. Dropouts were followed up through qualitative interviews. Results: A total of 20 participants (17 females and 3 male; mean age 44.2, SD 16.4 years) started the IDT-O program, and 35% (7/20) completed all 12 modules. Ten (8 females) out of 13 dropouts were interviewed. Both quantitative and qualitative findings showed that participants were generally satisfied with the content and design of the intervention. Those who completed the IDT-O lost some weight (mean 2.0%, 95% CI −1.09 to 5.13), reported improved dietary habits (effect size [ES] 0.25, 95% CI −0.51 to 1.00), increased physical activity (ES 0.93, 95% CI −0.08 to 1.87), and improved psychosocial functioning (distress: ES 0.43, 95% CI 0.‐0.37 to 1.19; avoidance: ES 0.67, 95% CI −0.18 to 1.48), 6 months after completing the treatment. The qualitative analysis of the interviews revealed “The programme was OK, but it does not suit everyone” as the main theme. The main themes were based on the 3 subthemes: “It wasn’t for me,” “There were good things,” and “There are things to improve.” Conclusions: The findings indicate that the IDT-O holds potential as a treatment for people with obesity, although one limitation is that only 35% (7/20) of the participants completed the pilot program. Improvements in lifestyle habits and psychosocial functioning were observed in those who completed the IDT-O, but these findings are preliminary and need to be confirmed in a more comprehensive study. The issue of nonadherence underscores the importance of both thoroughly assessing patients before treatment and further development of IDT-O programs. Trial Registration: ClinicalTrials.gov NCT04150445; https://clinicaltrials.gov/study/NCT04150445
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Transcutaneous auricular vagus nerve stimulation to alleviate metformin-associated gastrointestinal adverse events and optimize glycaemic control: a randomized, sham-controlled pilot trial protocol

BackgroundGastrointestinal adverse events (GI AEs) are the main dose-limiting side effects of metformin in type 2 diabetes mellitus (T2DM), reducing adherence and compromising long-term glycaemic control. Current strategies (dose adjustment or combination therapy) seldom address both tolerability and sustained metabolic efficacy. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that may modulate gut–brain–metabolic pathways—vagal reflexes, inflammation, intestinal barrier function, and enteroendocrine signaling—and thus improve drug tolerance while preserving glycaemic control.MethodsThis single-center, randomized, sham-controlled pilot trial will enroll 60 T2DM patients with metformin-associated GI AEs, randomized 1:1 to either the taVNS group or the sham control group. The intervention lasts 2 weeks with a follow-up at week 4. Assessments at baseline and follow-up include a validated Metformin Symptom Severity Score (total score 0–50; primary outcome), Bristol Stool Form Scale, bowel urgency, glycaemic/metabolic indices [fasting blood glucose (FBG), 2-h postprandial glucose (PG2h), glycated albumin (GA), fasting C-peptide, fasting insulin, HOMA-IR, ISI], and mechanistic biomarkers (GLP-1, 5-HT, IL-6, IL-10, TNF-α, D-lactate, DAO, bile acids). Safety monitoring includes routine hematology, liver and renal function tests.DiscussionBy combining clinical outcomes with targeted biomarker analyses in a randomized design, this pilot study will assess whether taVNS alleviates metformin-associated GI intolerance without impairing glycaemic efficacy, and will provide feasibility data, effect-size estimates, and biomarker selection for future confirmatory trials.Clinical trial registrationTrial registration International Traditional Medicine Clinical Trial Registry (ITMCTR) http://itmctr.ccebtcm.org.cn/, Identifier: ITMCTR2025001086.
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Interoceptive dysfunction and its neural correlates in schizophrenia: protocol for a cross-sectional multimodal MRI study

BackgroundInteroception—the perception and integration of internal bodily signals—is fundamental to emotion regulation, bodily self-awareness, and predictive coding. Emerging evidence suggests that interoceptive disturbances may contribute to core psychopathological features of schizophrenia. Our research group recently conducted a systematic review and meta-analysis demonstrating significant impairments in interoceptive accuracy and sensitivity among individuals with schizophrenia. However, the neural mechanisms underlying these deficits remain unclear.MethodsThis cross-sectional protocol will recruit 30 individuals with schizophrenia and 30 age- and sex-matched healthy controls. Participants will complete (1) behavioral interoceptive assessment using the heartbeat counting task; (2) subjective interoceptive questionnaires, including the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Body Perception Questionnaire (BPQ); (3) clinical symptom ratings (PANSS, HAM-A, HAM-D); and (4) cognitive testing (TMT, animal fluency, DSST). All participants will undergo multimodal MRI scanning, including structural T1-weighted imaging, resting-state fMRI, and diffusion tensor imaging. Neuroimaging data will be preprocessed and analyzed using DPABISurf, SPM12, and GRETNA. Expected Results: We anticipate that individuals with schizophrenia will show reduced interoceptive accuracy, altered subjective interoceptive awareness, and abnormal intrinsic neural activity and connectivity within interoception-related circuits, including the anterior insula, anterior cingulate cortex, amygdala, and thalamus. Structural abnormalities within thalamo-cortical pathways are also expected. Interoceptive deficits are hypothesized to correlate with symptom severity and cognitive performance.ConclusionsThis study will provide an integrated characterization of interoceptive dysfunction and its neural correlates in schizophrenia. Findings may advance understanding of bodily self-disturbance and emotional dysregulation and support the development of future interoception-focused therapeutic approaches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2500110551.
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A Digital Inclusion Intervention to Improve Access to a Digital Health Intervention Among Digitally Excluded Adults: Mixed Methods Pilot Randomized Controlled Trial

Background: The National Health Service 10-year health plan emphasizes an increasing shift toward digital health care delivery. However, there is limited research on how best to support, engage, and include individuals who are digitally excluded. As health care services become more digitally driven, evidence-based interventions are needed to address digital exclusion and ensure equitable access to care, particularly for people living with long-term conditions. Objective: This study aimed to evaluate the feasibility and acceptability of providing digital literacy training alongside a digital health intervention (DHI; Ex-Tab intervention), compared with providing a DHI alone. Kidney Beam, a DHI designed to promote physical activity and improve quality of life in people with chronic kidney disease (CKD), was used as an exemplar DHI. Methods: This mixed methods, single-site pilot randomized controlled trial recruited 40 adults with CKD who were digitally excluded. Digital exclusion was defined as lacking access to a Wi-Fi–enabled digital device or having a Digital Health Care Literacy Scale (DHLS) score of <7 (range 0‐21). Participants were randomized 1:1 to receive either the Kidney Beam Ex-Tab intervention or Kidney Beam alone (control). The intervention group received a Wi-Fi–enabled iPad on loan with Kidney Beam preinstalled, digital literacy training, and ongoing support to access the 12-week Kidney Beam program (twice weekly live exercise and education sessions). The control group received sign-up instructions for Kidney Beam only. Feasibility outcomes were assessed against a priori progression criteria and included screening, recruitment, retention, adherence, safety, and acceptability. Secondary outcomes included the Kidney Disease Quality of Life Questionnaire, Chalder Fatigue Questionnaire, and Patient Health Questionnaire-4. Outcomes were measured at baseline and 12 weeks. Acceptability and user experience were explored through semistructured interviews with participants from both groups at 12 weeks (n=25). Results: Between September 2023 and September 2024, a total of 169 individuals were screened and 40 were enrolled (median age 66.5 years; 20 male individuals; median DHLS score: 4). Twenty-one participants were randomized to the Kidney Beam Ex-Tab group and 19 to the Kidney Beam alone group. Of the 40 participants, 35 (88%) completed the 12-week follow-up (intervention: n=18; control: n=17). All prespecified feasibility criteria for recruitment, retention, adherence, and safety were met. Qualitative findings indicated that the tablet loan and digital literacy training were acceptable and highly valued, enhancing confidence, motivation, and DHI engagement. Providing loaned devices was particularly important for overcoming access barriers, especially for participants unable to afford their own device. Conclusions: Providing Wi-Fi–enabled devices and digital literacy training alongside a DHI was feasible and acceptable for people with lower digital literacy levels. The findings support progression to a future definitive multicenter trial or implementation study and offer transferable insights for the design of digital inclusion strategies for other long-term health conditions. Trial Registration: ClinicalTrials.gov NCT04872933; https://clinicaltrials.gov/study/NCT04872933
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STAT+: Roche to launch another Elevidys trial, with eyes on European approval

In an attempt to win European approval for the controversial medicine, Roche said Thursday it would run another trial of the Duchenne muscular dystrophy gene therapy Elevidys. 

The Swiss company’s move comes after European regulators last year gave a negative review to the therapy, saying it had failed to demonstrate long-term benefits for patients with the degenerative muscle condition. Roche has rights to the therapy outside the U.S., where it is marketed by its developer, Sarepta Therapeutics.

Roche said the Phase 3 trial will generate the type of evidence that could lead to a resubmission with European officials and to applications with regulatory agencies in other parts of the world. The study will evaluate the safety and efficacy of Elevidys versus placebo over 72 weeks in roughly 100 boys at the early stages of the disease. 

Continue to STAT+ to read the full story…