International Journal of Clinical Trials

Comparing a multicomponent intervention versus a single component intervention for people with co-occurring substance use and mental health disorders: study protocol of a hybrid type I trial

Paige M. Shaffer — 2025-10-23

Background: Substance use and mental health are growing public health problems in the United States. People with co-occurring mental health and substance use disorders (COD) often have complex social determinants of health (SDOH) needs and struggle to engage in treatment. Linkage and multicomponent wraparound interventions, including maintaining independence and sobriety through systems integration, outreach and networking (MISSION), have gained popularity as solutions to increase treatment engagement and address behavioral health and SDOH needs of clients with COD. This protocol offers an overview of an effectiveness trial and a process evaluation of MISSION being delivered in a city public health setting.

Methods: This study will use a hybrid type I effectiveness and implementation design with a randomized controlled trial. People with COD will be randomized to one of two treatments: a multicomponent COD intervention (MISSION), or a peer delivered linkage-only intervention (PLS). Secondary aims include the examination of mechanisms of action and a sequential mixed methods process evaluation to inform the sustainability and future implementation of MISSION.

Conclusions: This trial will help determine the effectiveness of MISSION compared to PLS to improve engagement, and reduce substance use and mental health symptoms. This trial is the first to implement MISSION within a public health department setting which has important implications for policymakers and treatment providers within behavioral health fields.

Trial Registration: Trial registration number is NCT05713695, registered on 27 January 2023.

Home-based prehabilitation before total knee arthroplasty: a randomized controlled trial protocol on feasibility and functional outcomes

José Carlos dos Santos Albarello — 2025-10-23

Background: Total knee arthroplasty is a common surgical intervention for patients with end-stage knee osteoarthritis. Prehabilitation programs have been shown to improve postoperative outcomes, however, access to in-person rehabilitation remains a barrier for many patients. Home-based exercise programs may offer a viable alternative to improve preoperative physical function and optimize recovery.

Methods: This study describes the protocol for a randomized controlled trial evaluating the feasibility and effects of a home-based prehabilitation intervention on physical function recovery for patients awaiting total knee arthroplasty. This is a prospective, two-arm, parallel-group, superiority randomized controlled trial, conducted at a national referral hospital. Patients scheduled for primary total knee arthroplasty will be randomized into either an experimental group receiving a structured home-based exercise program or a control group receiving standard hospital instructions. The intervention will be remotely monitored through digital communication tools. Feasibility outcomes include adherence rates and the occurrence of adverse events, while the study also assesses functional performance measures [Timed up and go test (TUG), sit-to-stand test], self-reported pain and function (WOMAC), postural balance, and knee extensor torque. Statistical analyses will be performed using a linear mixed-effects model (LMM) to assess intervention effects over time.

Conclusions: This trial will provide essential data on the implementation of home-based prehabilitation and its potential to improve access to rehabilitation for patients with limited healthcare resources. If feasible, this approach could be integrated into standard preoperative care, reducing barriers to rehabilitation and enhancing post-surgical recovery.

Trial registration: Approval from the local ethics committee (7.098.085) and was registered at clinicaltrials.gov (RBR-3m77djm).

Improving treatment outcomes in chronic myeloid leukaemia patients using imatinib and artesunate combination therapy: a randomized controlled clinical trial protocol (IMART-trial)

Oluwatoyin T. Famurewa — 2025-10-23

Background: Chronic myeloid leukaemia (CML) is a haematological cancer accounting for 15% of newly diagnosed cancers in adults. Imatinib, a tyrosine kinase inhibitor (TKI), has transformed a once-fatal disease into a manageable condition. However, about one-third of patients develop resistance to the drug, increasing the disease burden and risk of progression, especially in low-and middle-income countries where newer TKIs are expensive and limited. Artesunate, an antimalarial drug, has been reported to exhibit anti-neoplastic effects alone or in synergy with other anti-neoplastic agents.

Methods: This randomised controlled trial will evaluate the clinical efficacy of the combination therapy of imatinib and artesunate in imatinib-naive patients and sub-optimal responder patients as defined by the European LeukemiaNet. Patients will be given imatinib at 400 mg daily, while the test groups will also receive artesunate (200 mg daily for 14 days monthly). Serial clinical assessments, laboratory investigations and pharmacokinetic analyses will be conducted at 1, 3, 6, 9, and 12 months into therapy. The treatment outcomes for each patient will be determined using the complete blood count and BCR::ABL1 quantification.

Conclusions: An imatinib-artesunate combination therapy could be a cost-effective solution to the development of imatinib resistance in newly diagnosed CML patients and possible alternative option in the management of sub-optimal response to imatinib.

Trial registration: Trial registration number is NCT07022743.

Efficacy of synchronous, virtual cognitive behavioral therapy for insomnia across phases of cancer survivorship: a study protocol

Kelcie D. Willis — 2025-10-23

Background: Chronic insomnia affects up to 50% of cancer survivors, contributing to emotional distress, fatigue, and reduced quality of life. Cognitive behavioral therapy for insomnia (CBT-I) is the recommended first-line treatment, yet access remains limited, particularly for cancer survivors across different phases of survivorship. This study evaluates the efficacy of a synchronous, virtual CBT-I intervention targeted for cancer survivors survivorship sleep program (SSP) across curvivors, those in active treatment, and metavivors.

Methods: This randomized controlled efficacy trial will enroll 198 cancer survivors with clinically significant insomnia and will randomize participants 1:1 to the SSP (n=99) or enhanced usual care (EUC; n=99). SSP consists of four weekly 45-minute sessions and one booster session at week 6. The primary outcome is change in insomnia severity (ISI) from baseline (T0) to week 10 (T2). Secondary outcomes include subjective (sleep diary) and objective (Fitbit) sleep metrics, emotional distress, fatigue, sleep medication use, perceived cognitive functioning, work presenteeism/absenteeism, and health behaviors, assessed acutely (week 6; T1) and 3-months post-SSP (week 18; T0-T3). Exploratory outcomes include acceptability metrics and treatment effects by survivorship phase.

Conclusions: This trial addresses major gaps in the CBT-I literature by evaluating key subjective and objective sleep outcomes for cancer survivors across various phases of treatment. Findings will inform the scalable delivery of CBT-I in oncology, advancing access to evidence-based insomnia care.

Trial registration: NCT06181643.

A study protocol for assessing the efficacy of Guduchyadi Ghrita in mild neurocognitive disorder: a placebo-controlled trial with brain-derived neurotrophic factor evaluation

Priya H. Soni — 2025-10-23

Background: Mild neurocognitive disorder (mNCD), a preclinical stage of dementia, is becoming a significant public health concern, especially among the aging population. Brain-derived neurotrophic factor (BDNF) has emerged as a key biomarker for cognitive health. Guduchyadi Ghrita, an Ayurvedic formulation rich in nootropic, Rasayana, and antioxidant herbs, has shown promise in improving cognitive functions, including memory and attention, in preliminary studies. Pratimarsha Nasya, known for its brain-targeted therapeutic effects, may enhance the bioavailability of these compounds. This study aims to evaluate the efficacy of Guduchyadi Ghrita with Pratimarsha Nasya in improving cognition and BDNF levels in individuals with mNCD.

Methods: This randomized, placebo-controlled, open-label, single-centre clinical trial will involve 80 participants diagnosed with mNCD according to DSM-V criteria. Group A will receive 12 gm/day of Guduchyadi Ghrita orally and 2 drops per nostril of Pratimarsha Nasya for 60 days, following Deepana-Pachana and Mridu Virechana. Group B will receive a placebo (roasted semolina capsules) and cognitive stimulation activities for 60 days. Primary outcomes will include improvements in cognition, assessed using the Montreal cognitive assessment (MoCA). Secondary outcomes will involve changes in plasma BDNF levels, quality of life (QOL-AD), and daily functioning (Bristol ADL scale).

Conclusions: This study will assess the potential of Guduchyadi Ghrita and Pratimarsha Nasya in enhancing cognitive function and promoting neuroplasticity in individuals with mNCD, with a focus on BDNF as a biomarker.

Trial registration: The trial is registered with the Clinical Trials Registry of India (CTRI) (REF/2025/04104935).

Navigating the global shift: prospects and challenges in the clinical research enterprise

Cliff N. Ntenga — 2025-10-23

In recent years, the conduct of clinical trials in developing countries has increased markedly, reflecting a broader shift of the clinical research enterprise toward non-traditional geographic regions. This expansion is driven by multiple factors including greater availability of research participants, decreased costs of conducting research and, in some cases, less restrictive regulatory environments. While these underlying forces present valuable opportunities to the clinical research enterprise system, they also introduce complex scientific, ethical, and regulatory challenges. Nevertheless, if the challenges are navigated prudently, the globalization of clinical research trials may hold considerable potential to accelerate the development of innovative medical therapies that could contribute meaningfully to addressing the global health needs.

Enhancing dermatology clinical trials: optimizing sites and strategies for success in India

B. S. Chandrashekar — 2025-10-23

India’s diverse patient population, cost-effective ecosystem and high prevalence of dermatological conditions like chronic inflammatory skin diseases, pigmentary disorders, alopecia and infectious diseases, etc. make it a prime destination for global clinical trials. This article is based on author’s experience in dermatology clinical research, web-based information from public domain including clinical trial registries, regulatory guidelines, review of literature, feasibility templates from sponsors and key industry conferences. It is the first of its kind to outline strategic approaches for optimizing dermatology clinical trial in India. This paper recapitulates importance of advanced diagnostic tools, site setup, infrastructure, regulatory compliance, ethical governance and institutional ethics committee (IEC) in enhancing site’s credibility and attracting sponsors. Additionally, it highlights the research gaps in dermatology and provides a roadmap for sponsors, CROs and investigators aiming to conduct ethical, efficient and impactful dermatology trials in India. These insights aim to equip Indian dermatology sites to attract and manage high-quality clinical trials across all phases.

The impact of workplace stress on nursing professionals’ well-being and balance: a silent killer

Binu Joe — 2025-10-23

Workplace stress is a pervasive threat to the physical and psychological health of nursing professionals, affecting their well-being, work-life balance, and patient outcomes. The demanding nature of the nursing profession, particularly in resource-constrained environments, places nurses at high risk for chronic stress. This umbrella concept analysis aims to synthesize and analyze existing conceptual literature on workplace stress and its implications for the well-being and balance of nursing professionals. A systematic umbrella review methodology was employed, retrieving reviews and concept analyses from five databases (PubMed, CINAHL, Scopus, PsycINFO, Web of Science). A total of 43 eligible studies (systematic reviews, meta-analyses, and concept analyses) published between 2000 and 2024 were analyzed. Conceptual frameworks were mapped using Walker and Avant's and Rodgers’ evolutionary methods of concept analysis. Common antecedents of workplace stress include high workload, role ambiguity, poor leadership, and organizational injustice. Consequences span psychological distress, burnout, emotional exhaustion, physical illness, and attrition. Key attributes include chronic exposure to stressors, emotional labor, and perceived lack of control. Interventions such as mindfulness-based stress reduction, improved leadership, and supportive work environments show moderate success. Workplace stress remains a silent but potent killer of nursing well-being. Clear conceptual understanding, proactive policy measures, and system-wide interventions are needed to safeguard nurse health and sustain quality care.

Factors influencing response to neoadjuvant chemoradiotherapy in rectal cancer: the role of serum carcinoembryonic antigen and tumor size

Vijay Kumar Saini — 2025-10-23

Neoadjuvant chemoradiotherapy (NACRT) is a pivotal component in the management of locally advanced rectal cancer (LARC), offering the advantages of tumor downstaging, enhanced resectability, and potential for sphincter preservation. Nevertheless, a heterogeneous response to NACRT exists among patients. There is a pressing need to identify reliable predictive factors that can guide therapeutic decisions and patient stratification. Among these, pre-treatment serum carcinoembryonic antigen (CEA) levels and primary tumor size have been extensively explored as potential markers of therapeutic efficacy. This paper critically evaluates current evidence linking these parameters to the likelihood of achieving favorable pathological response post-NACRT, including complete tumor regression.

Predictive modeling of infectious disease outbreaks: harnessing artificial intelligence for early detection and response

Gaurav Bajaj — 2025-10-23

Background: Artificial intelligence (AI) has become a transformative instrument in public health to monitor and forecast infectious disease outbreaks. AI-based predictive models enable early detection and quick response mechanisms which present potential superiority over traditional systems. The research investigation sought to evaluate public health professionals' perceptions alongside their usage patterns and the associated benefits and concerns regarding AI integration for disease prediction.

Methods: Researchers implemented a qualitative approach among 100 public health stakeholders through structured questionnaires and thematic analysis. The quantitative measurements recorded frequency counts alongside tool usage metrics and perceived impacts while qualitative responses brought forward thematic concerns and participant expectations.

Results: The survey participants strongly agreed that AI technology enhances outbreak prediction accuracy (78%) and enables both fast outbreak detection (85%) and expedited resource reallocation (70%). The main issues which stakeholders brought up included privacy concerns about data (66%) and obscurity of algorithms (58%) and excessive machine-driven output dependency (47%). Among the AI tools employed machine learning models were the most prevalent followed by deep learning algorithms. Prediction models are used by 52.5% of respondents according to survey results. Stakeholders expressed positive views toward AI integration as 81% of them endorsed its implementation but approached it with the request to combine computer-generated forecasts with human expert analyses.

Conclusions: The study confirms the increasing acceptance and experienced value of AI when monitoring infectious disease. Despite the benefits, moral and operational challenges highlight the importance of transparent, human focused AI design. Future efforts should focus on improving equal access to trust, purpose and prediction tools.

Bridging gaps in chronic kidney disease management: insights from clinicians on real-world practices

Vishwa Mehta — 2025-10-23

Background: Chronic kidney disease (CKD) is frequently underdiagnosed in early stages, especially in India, due to its asymptomatic onset, limited diagnostics, and delayed referrals. This study aimed to assess real-world CKD management practices and gaps among Indian clinicians.

Methods: A structured survey of 40 clinicians across 11 cities in India captured data on CKD staging, treatment preferences, and complication(s) management.

Results: Early-stage CKD (3a/3b) was most commonly diagnosed stage of CKD. Moreover, diabetic nephropathy was prevalent in 55% cases, followed by hypertensive nephropathy in 35% cases and other risk factors in 10% cases. Sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists (finerenone), and glucagon-like peptide-1 receptor agonists were preferred in diabetic CKD. Metformin was often de-escalated at Stage 3b. For complications, sodium polystyrene sulfonate and darbepoetin alfa were commonly used for hyperkalaemia and anaemia, respectively. Budesonide emerged as a key choice in IgA nephropathy.

Conclusions: Despite increasing use of evidence-based therapies, significant gaps remain in early diagnosis and uniform management, highlighting the need for improved awareness and access to newer agents to optimize CKD care.

Comparison of salivary and serum IgG and IgA levels with total protein in oral lichen planus

Sri Sathya Naga Mallika Bokka — 2025-10-23

Background: Lichen planus is the common dermatologic disease with oral manifestations. It is an immunologically based, chronic, inflammatory, mucocutaneous disorder with undetermined etiology. The role of salivary immunoglobulins in the immunopathogenesis and the clinical course of oral mucosal diseases, have not been yet studied comprehensively. IgG and IgA being the predominant immunoglobulins in normal serum. Secretory IgA constitutes the predominant immunoglobulin isotype in secretions, including saliva.

Materials: Followed by informed consent 20 patients diagnosed with Lichen planus are enrolled in the study from the Department of Oral and Maxillofacial Pathology, MNR Dental College and Hospital, Sangareddy. A new particle-enhanced turbidimetric immunoassay using mono-specific sheep antibodies on the SPAPLUS® analyzer is used to determine the soluble antigen concentration (IgG, IgA).

Results: The results showed that the mean serum IgG and IgA levels in lichen planus patients is higher when compared with controls. There is a significant difference in the mean IgG and IgA levels levels in both the study groups (<0.001; sig). The current study results showed that the mean salivary IgG and IgA levels in lichen planus patients is elevated compared to controls. A significant difference is found in the mean IgG and IgA levels in patients and controls (<0.001; sig).

Conclusion: The results might conclude that elevated levels of serum and salivary IgG and IgA show that humoral immunity is implicated in the pathogenesis of oral lichen planus. Further studies with more number of cases could throw light on the etiology and pathogenesis of the disease.

Dawn of auditory restoration: meta-review of genetic therapy advances for congenital hearing loss

Tanvir Hussain — 2025-08-26

Congenital hearing loss (CHL), affecting 1-3 per 1000 newborns globally, represents a paradigm shift in therapeutic development with the advent of genetic interventions. This meta-review synthesizes evidence from 42 clinical and preclinical studies (2020-2025) demonstrating that adeno-associated virus (AAV)-mediated gene therapy has successfully restored auditory function in patients with autosomal recessive deafness 9 (DFNB9), with mean auditory brainstem response (ABR) thresholds improving from 106±9 dB to 52±30 dB within one-month post-intervention. Younger patients (5-8 years) exhibited near-complete recovery, while adults showed clinically significant improvements. The emergence of novel delivery vectors (including engineered AAVs and lipid nanoparticles), CRISPR-based editing strategies, and innovative cellular entry pathways (AAVR2 receptor) has expanded the therapeutic landscape. Despite challenges in vector tropism, immune responses, and accessibility, genetic therapies are poised to transform CHL management from amplification to biological restoration. Future research must prioritize solutions for dominant genetic forms, optimal intervention timing, and cortical reintegration pathways.

The impact of “internet of things”: advancing patient monitoring and health outcomes to enhance healthcare quality: a systematic review

Ritu Kumari — 2025-10-23

The internet of things (IoT) has emerged as a transformative force in healthcare, reshaping patient monitoring, data collection, and clinical decision-making. As the global healthcare landscape becomes increasingly digitized, understanding the contributions of IoT to quality enhancement is critical. This systematic review explores the current evidence on the impact of IoT on patient monitoring and health outcomes, focusing on its role in improving healthcare quality. A comprehensive search of PubMed, Scopus, IEEE Xplore, and Google Scholar databases was conducted for studies published between January 2015 and May 2025. Keywords included “IoT in healthcare,” “patient monitoring,” “health outcomes,” and “quality improvement.” Studies were included if they focused on IoT applications in healthcare settings with measured outcomes related to patient care or quality. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed. A total of 58 studies were included. The majority demonstrated significant improvement in early detection of clinical deterioration, chronic disease management, remote patient monitoring, and reduction in hospital readmissions. IoT was found to enhance real-time decision-making, lower operational costs, and improve patient satisfaction and safety metrics. IoT plays a pivotal role in advancing healthcare delivery by enhancing monitoring capabilities and health outcomes. However, ethical challenges, cybersecurity concerns, and interoperability barriers remain. Strategic investments and regulatory frameworks are essential for sustainable IoT integration.