International Journal of Clinical Trials

Effectiveness of metabolic modulation in treating post-vaccination syndrome: study protocol for a prospective and randomized controlled trial

Matthew Halma, Joseph Varon — Thu, 22 Jan 2026 00:00:00 +0530

Background: Post-acute COVID-19 vaccination syndrome (PACVS) emerged as a rare complication of the COVID-19 vaccination campaigns, which began in late 2020, when the first trials were underway, and continued to the present day, when COVID-19 vaccines are available for use. While their uptake peaked in the years of 2021 and 2022, a rare side-effect was the presence of a myalgic encephalitis/chronic fatigue syndrome (ME/CFS) phenotype. This population has limited treatment options available, and surveys show that many are trying poorly validated treatment protocols with limited success.

Methods: One hundred patients presenting with PACVS with a lab-confirmed diagnosis will be enrolled for a 3-month study. Patients are randomized to intervention and placebo groups and provided with a combined metabolic modulator, called ViTAL SCAN (vitamin C, taurine, acetyl L-carnitine, serine/sarcosine, creatine/citrulline, acetylcysteine/ arginine, and NMN) in the intervention group, and unflavoured rice protein powder with vitamin C in the placebo group. Baseline measurements of a combined biomarker panel, including metabolic and inflammatory markers, as well as heart rate variability, physical performance, and self-rated quality of life.

Conclusions: Treatment of PACVS currently has a lack of evidence for the efficacy of treatment interventions for the disease. While several interventions have been proposed, their prospective clinical usefulness relies on arguments from mechanism or analogy from related disorders (e.g., long COVID-19, ME/CFS, acute COVID-19 infection). Limited data exists on the clinical efficacy of treatments for PACVS. This research proposal tests a combined nutraceutical for the purpose of improving metabolic parameters.

Trial Registration: Clinical Trials Gov NCT number will be obtained.

Effectiveness of analgosedation protocol on duration of mechanical ventilation in adults with trauma: a pragmatic, cluster and randomized study

Thu, 22 Jan 2026 00:00:00 +0530

Background: Sedation practices in trauma intensive care unit (ICU) patients requiring invasive mechanical ventilation (IMV) are still not well studied. While protocol-directed sedation (PDS) and spontaneous awakening trials (SAT) have improved outcomes in non-trauma groups, their use in trauma patients-who often experience higher pain levels, substance use, and complex injuries-is uncertain. Analgosedation, which gives priority to analgesics before sedatives, may have benefits in this group but has not been thoroughly tested in trauma ICUs.

Methods: This is a 24-month, single-center, pragmatic, cluster-randomized controlled trial with a crossover design comparing an analgosedation (+SAT) protocol to a traditional PDS+SAT protocol. Adult trauma ICU patients receiving IMV and expected to need continuous sedation for at least 48 hours are enrolled. The primary outcome is ventilator-free days at day 10 (VFD-10). Secondary outcomes include time to weaning, sedative and opioid exposure, delirium-and coma-free days, self-extubation, ICU/hospital length of stay, and mortality. Interventions are implemented throughout the ICU each month, with crossover randomization. A waiver of informed consent was granted due to the patient's incapacity and the minimal risk involved. Data will be analyzed using intention-to-treat principles and time-dependent Cox models to account for clinical confounders.

Conclusions: This trial aims to determine whether an analgosedation strategy improves clinically meaningful outcomes in mechanically ventilated trauma ICU patients compared to a traditional sedation approach. The findings will address a critical evidence gap and inform sedation protocols tailored to trauma populations, potentially enhancing recovery and decreasing ICU workload.

Trial registration: ClinicalTrials.gov Identifier: NCT05751863 Protocol version: 4.0.

Tele-cognitive training on patients with stroke: a protocol of a feasibility randomized controlled study

Pritha Roy, Keshav J. Kumar, Srijithesh P. Rajendran — Thu, 22 Jan 2026 00:00:00 +0530

Background: Traditional in-person cognitive rehabilitation is often inaccessible to patients due to physical limitations, travel constraints, and financial barriers. On the other hand, home-based cognitive training programs frequently lack therapist supervision. This study protocol aims to explore the feasibility of therapist-led tele-cognitive training (TCR) delivered through videoconferencing for patients with post stroke cognitive impairment (PSCI).

Methods: In this randomised feasibility study, 58 patients will be randomly assigned to intervention or treatment-as-usual (TAU) groups. The intervention group will receive 18 comprehensive tele-cognitive training sessions (4-5 per week). Cognitive assessments will include the digit span, Corsi-block tapping, controlled oral word association, animal naming, Stroop, auditory verbal learning, and design construction tests. Secondary outcomes will include the modified Barthel index, stroke-specific quality of life questionnaire, hospital anxiety and depression scale, NIMHANS cognitive screening scale, perceived deficit questionnaire, neuropsychiatric inventory questionnaire (NPI-Q), and visual analogue scale (VAS). Assessments will be conducted at baseline (T0) and post-intervention (T1). A feasibility questionnaire will be completed post-training by the intervention group and the researcher, and a three-month follow-up (T2) with rating scales will assess longer-term outcomes.

Conclusions: This study protocol aims to enhance remote access to cognitive retraining, particularly in low- to middle-income countries.

Trial registration: Trials registry of India, no. CTRI/2023/02/049481.

Trial design and protocol of randomized controlled trial evaluating the efficacy of a non-invasive topical pain numbing device for prophylactic analgesia during routine vaccination in children

Swetha Madhuri Pulla, Jyothi Naik, Thirunavukkarasu Arun Babu — Thu, 22 Jan 2026 00:00:00 +0530

Background: Pain associated with vaccination is a common cause of anxiety among children and their parents. While pharmacological and non-pharmacological interventions have been explored to reduce pain, their use is not widespread in practice. Cryoanalgesia using a non-invasive pain numbing device is a novel approach that has shown promise during minor procedures.

Methods: This is a prospective, double-blinded, randomized controlled trial evaluating the efficacy and safety of a non-invasive topical pain numbing device in reducing pain during routine childhood vaccination. Children aged 6 months to 10 years presenting to the pediatric OPD for immunization will be recruited. Participants will be randomly allocated to either the intervention (device) or control (sham device) group using block randomization. Pain will be assessed using the FLACC scale at 0-, 5- and 15-minutes post-vaccination.

Conclusions: If the device proves effective in reducing vaccination-associated pain, it could be implemented widely to improve vaccine compliance and reduce vaccine hesitancy.

Trial Registration: Clinical trials registration number is CTRI/2025/03/083734.

A study protocol for assessing the efficacy of Shatavaryadi Kashaya and Shatavari Ghrita ointment in the management of genitourinary syndrome of menopause: an open labelled randomized standard-controlled clinical trial

Anjana B. Thanki, Shilpa Donga — Thu, 22 Jan 2026 00:00:00 +0530

Background: Genitourinary syndrome of menopause (GSM) is a chronic, progressive condition in postmenopausal women characterized by genital, sexual and urinary symptoms due to estrogen deficiency. Ayurveda attributes such degenerative symptoms to Vata dominance and Dhatukshaya in Jara Avastha, with management focused on Rasayana and Snehana therapies. This study aims to provide efficacy of oral administration of Shatavaryadi Kashaya along with per vaginal application of Shatavari Ghrita ointment in the management of GSM and to compare it with standard treatment using Multivitamins and Estriol cream.

Methods: Open-labelled, randomized, standard-controlled clinical trial, participants, patients fulfilling inclusion criteria of genitourinary syndrome of menopause; interventions: group A will receive Shatavaryadi Kashaya (40 ml orally twice daily) and Shatavari Ghrita ointment (2 gm per vaginal application daily with applicator), while group B received Weltive 4G (oral multivitamin) and Evalon cream (0.5 gm per vaginal application twice weekly) for 60 days. Primary outcome measures include improvements in Vaginal Health Index (VHI), Female Sexual Health Index (FSHI) and urinary tract infection symptoms assessment by UTISA, secondary outcome includes changes in the Vaginal Maturation Index (VMI) measured by Pap smear.

Conclusions: This trial aims to assess the potential of Shatavaryadi Kashaya and Shatavari Ghrita ointment as Ayurveda treatment for Genitourinary syndrome of menopause, offering a promising non-hormonal alternative to conventional estrogen therapy.

Trial registration: The trial is registered with the Clinical Trials Registry of India (CTRI) CTRI/2025/07/091397.

A systematic review of statistical approaches in clinical studies for atopic dermatitis treatment

Maheshvari Patel, Nayan Patel, Rutuja Patil, Shambhavi Srivastava — Thu, 22 Jan 2026 00:00:00 +0530

Biostatistics plays a pivotal role in clinical research by supporting accurate data analysis and interpretation, which are essential for drawing valid and evidence-based conclusions. In studies of atopic dermatitis (AD), a chronic, relapsing inflammatory skin condition, statistical methods are critical for evaluating clinical outcomes such as SCORAD scores, skin hydration, and patient-reported symptoms. As the number of trials investigating the efficacy and safety of skin care products for AD continues to grow, the quality and appropriateness of the statistical techniques used in these studies warrant close examination. This systematic review assessed statistical methods employed in clinical trials of skin care interventions for AD published between January 2020 and April 2025. Following PRISMA guidelines, a comprehensive search of PubMed was conducted, and 16 studies meeting the inclusion criteria were analysed in detail. A wide range of statistical methods was reported, including t-tests, ANOVA, ANCOVA, chi-square tests, and non-parametric alternatives such as the Wilcoxon signed-rank and Mann–Whitney U tests. Some studies also applied advanced techniques like mixed-effects models and ROC analysis. While most methods were generally appropriate for the study designs, frequent shortcomings were observed in the testing of assumptions and consistency of statistical reporting. These methodological gaps may limit the interpretability and reproducibility of trial outcomes. The findings highlight the need for improved statistical rigor and greater transparency in the analysis and reporting of clinical trials assessing skin care products for AD, ultimately to support more robust and reliable conclusions in dermatological research.

E6(R3) is here: what it means for the future of clinical trials

Thu, 22 Jan 2026 00:00:00 +0530

The ICH E6 Good Clinical Practice (GCP) guideline provides internationally harmonized ethical and scientific standards for the conduct of clinical trials involving human participants. While the E6(R2) revision introduced risk-based monitoring and strengthened sponsor oversight, rapid advances in trial complexity, digital technologies, and patient-centric and decentralized research models necessitated further modernization. The recently revised ICH E6(R3) guideline builds on the principles of ICH E8(R1) and emphasizes quality-by-design, proportionate risk-based approaches, and identification of factors critical to trial quality. It expands guidance on data governance, innovative trial designs, use of digital tools, and inclusive participant recruitment, while clarifying stakeholder roles and responsibilities. This article reviews the evolution of ICH E6 and discusses the key changes and practical implications of E6(R3) for the conduct of efficient, ethical, and globally acceptable clinical trials.

Impact of artificial intelligence on empowering the future of nursing professionalism, educational and clinical advancements: an umbrella review on AI-driven transformation

Thu, 22 Jan 2026 00:00:00 +0530

Artificial Intelligence (AI) is rapidly transforming healthcare by augmenting clinical decision-making, streamlining workflows, and personalizing education and patient care. Nursing, as the largest healthcare workforce, stands at the forefront of this transformation. This review examines how AI-driven tools empower nursing professionalism, enhance educational models, and optimize clinical practice. A systematic umbrella concept analysis was conducted using PubMed, Scopus, CINAHL, and Web of Science databases. Literature published between 2010 and 2025 was reviewed. Eligible studies included original research, reviews, policy reports, and frameworks focusing on AI applications in nursing education, practice, and professional development. Data were synthesized thematically under three domains: professional identity, educational innovation, and clinical advancement. Sixty-five studies met inclusion criteria. Evidence suggests that AI supports professional autonomy through clinical decision support systems, predictive analytics, and digital documentation, reducing administrative burdens. In education, AI-enabled simulations, adaptive learning platforms, and virtual mentors enhance critical thinking and competency development. Clinically, AI improves patient monitoring, diagnostic accuracy, and personalized care delivery. However, ethical dilemmas, data privacy risks, and limited digital literacy remain significant barriers. AI offers transformative potential for strengthening nursing professionalism, integrating evidence-based education, and advancing patient-centered clinical practice. To harness these opportunities, investment in nurse-centered AI training, interdisciplinary collaboration, and policy frameworks is essential. Nursing must embrace AI as a partner technology to redefine future roles and leadership in digital healthcare ecosystems.

Stretching beyond the wound: a review of yogic interventions in repairing maternal affect, cortisol dysregulation, and postpartum somatic disorientation

Mahak Bhandari, Nawneet Kumar Kurrey, Kavita Madipalli — Thu, 22 Jan 2026 00:00:00 +0530

Following childbirth, most women show linked disruptions in affect regulation, hypothalamic-pituitary-adrenal (HPA) axis, and somatic orientation that may impede their emotional functioning and mother-infant relationships. Pharmacotherapy typically fails to adequately address these complex challenges. This manuscript is a narrative review that summarizes the findings of randomized trials, systematic reviews, and mechanistic studies on yoga-based interventions to address postpartum mood, cortisol regulation, and somatic disorientation. Results on the whole show that yoga is linked with decreases in depressive and anxiety symptoms, enhancements in perceived stress, and changes in HPA axis activity. Nevertheless, the various styles of yoga, dosing regimens, levels of supervision, and the use of small sample sizes with short follow-up periods contribute to the uncertainty of the conclusions. The emerging literature and reasonable biopsychosocial hypotheses indicate that yoga can be a practical supplement to standard postpartum care. The review provides a comment on the gaps in the methodology and gives suggestions on the possibility of normalizing protocols, outcome measures, and safety reporting to enhance future studies and make it more equal in its application.

Prospective observational study on etiological factors, clinical profile and pattern of metastases of colorectal cancer: in a rural population of Central India – a tertiary cancer centre study

Thu, 22 Jan 2026 00:00:00 +0530

Background: Colorectal cancer (CRC) incidence has increased in Asian countries with 2-4 times surge in colorectal cancer incidence and mortality. There is a significant interaction between lifestyle changes and genetic predispositions. This study, involving 332 patients from central India, investigates the demographic patterns, epidemiological aspects, pattern of metastases, and clinical profiles of patients from the rural central India.

Methods: A prospective observational study was performed at State Cancer Institute, NSCB Medical College in Jabalpur, focussed on all cases of colorectal carcinoma registered at our institution from 2017 to 2023. Staging followed the recent AJCC 8th edition and treatment as per the recent NCCN guidelines.

Results: Among 332 CRC patients (24.09% aged 0–39 years (mean 29.2), 75.91% >40 years (overall mean 48.3)), abdominal pain (50%, n=166) and tobacco use (45.18%, n=150) predominated. Stage III/IV (68.38%, n=227), liver metastases (n=78), and rectal tumours (49.72%, n=165). Rural residents (62.65%, n=208) and illiteracy (29.52%, n=98) were common. Right-sided CRC correlated with females (55%) and mucinous histology (23.1%). Young cases rose 3–5% annually, peaking post-COVID.

Conclusion: This tertiary cancer hospital study (2017-2023) highlights that 68.38 % of patients presented with Stage III/IV disease mostly from rural population. Most cases were sporadic, with no significant family history. Rectum was the most common site, and liver the predominant site of metastasis. Dietary habits indicate low fibre and high red meat intake may contribute to CRC risk. These findings highlight the need for early screening, public awareness, and targeted interventions to address modifiable risk factors in rural populations.

A cross-sectional analysis of clinical, hematological and psychosocial factors associated with alexithymia and somatic symptoms in patients with chronic kidney disease: insights from a South Indian cohort

Thu, 22 Jan 2026 00:00:00 +0530

Background: Chronic kidney disease (CKD) is increasingly recognized as a biopsychosocial condition, with emotional dysregulation and somatic symptoms representing important yet underexplored dimensions. This study aimed to examine the prevalence and predictors of alexithymia and somatic symptoms in CKD patients, highlighting clinical, laboratory and psychosocial interactions.

Methods: A cross-sectional study was conducted among 130 CKD patients (mean age: 54.9±13.8 years; 58.5% male). Psychometric assessments included the Toronto Alexithymia Scale (TAS-20) and the Patient Health Questionnaire (PHQ-15). Data were analyzed using Kruskal-Wallis, Mann-Whitney U, Spearman correlations and univariate and multivariate regression models.

Results: Alexithymia was present in 50.8% of participants, while somatic symptoms were reported in 46.9%. TAS scores were significantly associated with age (p=0.021) and diabetes mellitus (p=0.016). PHQ-15 scores showed limited associations, with significant differences across age groups (p=0.039) and borderline associations with CKD stage (p=0.052). Red blood cell (RBC) count emerged as the strongest predictor of both TAS (β=0.923, p<0.001) and PHQ-15 (β=0.239, p=0.006) scores. The multivariate model explained 85.4% of TAS variance (Adjusted R²=0.854), whereas PHQ-15 scores were less predictable (Adjusted R²=0.068). Caregiver burden was significantly higher among patients with alexithymia (p<0.0001).

Conclusions: Alexithymia and somatic symptoms are highly prevalent in CKD and shaped by biological and psychosocial determinants. Incorporating broader psychosocial assessments and caregiver support into CKD management could enhance patient outcomes and alleviate family burden.

Hypofractionated radiotherapy with weekly paclitaxel and carboplatin versus conventional fractionation radiotherapy with weekly cisplatin in carcinoma of the larynx and hypopharynx for response and toxicity assessment

Dhiraj Meshram, Balaji Shewalkar, Jitendra Patel, Punita Pant — Thu, 22 Jan 2026 00:00:00 +0530

Background: Conventional fractionated radiotherapy (CFRT) with weekly cisplatin is the standard of care for locally advanced laryngeal and hypopharyngeal carcinoma but is often limited by significant toxicity. This study evaluates hypofractionated radiotherapy (HFRT) combined with weekly low-dose paclitaxel and carboplatin as a more tolerable alternative. Objective of the study was to compare the tumor response and toxicity profiles of HFRT plus paclitaxel/carboplatin versus CFRT plus cisplatin.

Methods: Sixty-four patients with stage III–IVB carcinoma were randomized into two arms. Arm 1 received HFRT (63 Gy in 28 fractions) with weekly paclitaxel (30 mg/m²) and carboplatin (AUC 1.5). Arm 2 received CFRT (70 Gy in 35 fractions) with weekly cisplatin (30 mg/m²). Response was assessed via RECIST 1.1; toxicities were graded using RTOG/CTCAE criteria.

Results: At 6 weeks post-treatment, the complete response (CR) rate was 71.9% in arm 1 and 68.8% in arm 2. Arm 1 demonstrated a significantly improved safety profile, with lower rates of grade 3 mucositis (28.1% versus 43.8%) and grade 3 leukopenia (15.6% versus 28.1%). Additionally, grade 2 skin reactions (25% versus 37.5%) and nausea/vomiting (31.3% versus 53.1%) were less frequent in arm 1, leading to higher treatment compliance.

Conclusions: HFRT with weekly low-dose paclitaxel/carboplatin offers non-inferior efficacy and superior tolerability compared to standard CFRT. It is a viable therapeutic strategy for elderly or renal-compromised patients and in resource- constrained settings.

Efficacy of a novel supplement GlucoSEB PB™ for glucose management: an in vitro and clinical study approach

Abhijit Rathi, Sneha Potale, V. L. Rathi — Thu, 22 Jan 2026 00:00:00 +0530

Background: The objective of the study was to perform a comprehensive investigation of GlucoSEB PB™ using in-vitro digestion and a clinical study for evaluating its effects on sugar digestion and associated metabolic responses.

Methods: In-vitro digestion of a bread-chicken-patty as a food-matrix was performed using INFOGEST simulated semi-dynamic digestion protocol in presence and absence of GlucoSEB PB™. The sugars released were quantified. Further, for the clinical trial, a double-blind, randomized, crossover, placebo-controlled study was performed by randomizing 35-prediabetic subjects into test and placebo groups. Subjects were instructed to consume 2-capsules (test or placebo), 30-min prior to consumption of standard-meal, and blood-glucose related parameters were monitored.

Results: GlucoSEB PB™ effectively caused a net reduction in the available simple-sugars by 19.40% post in-vitro gastro-intestinal digestion. This was due to formation of oligosaccharides with dietary-fiber potential conferring prebiotic benefits. The findings of the clinical-study indicated an increase in blood-glucose levels until 45 and 60-min in the GlucoSEB PB™ and placebo groups, followed by a continuous decline for 3-h post-consumption of the standard-meal. GlucoSEB PB™ supplementation resulted in a 16.90% reduction in AUC over the placebo, signifying its role in controlling blood-glucose. Additionally, no variations were observed in insulin levels in both arms.

Conclusion: Notably, GlucoSEB PB™ was safe and showcased tolerability at the investigated dosage. No AEs/SAEs were reported during the entire investigation.

Correlation between magnetic resonance imaging-based radiological response after 8 weeks of neoadjuvant chemoradiotherapy and postoperative histopathological response in rectal adenocarcinoma

Vijay K. Saini, Gaurav Singh, Sudip Regmi, Shakeel Masood, Anshuman Pandey — Thu, 22 Jan 2026 00:00:00 +0530

Background: Neoadjuvant chemoradiotherapy (NACRT) is the standard of care for locally advanced rectal adenocarcinoma, facilitating tumor downstaging and improving surgical outcomes. Magnetic resonance imaging (MRI) is widely used to assess treatment response after NACRT; however, its ability to accurately predict histopathological tumor regression remains variable. Reliable radiological prediction is essential for individualized treatment planning and consideration of organ-preserving strategies.

Methods: This prospective observational study included 47 patients with mid or low rectal adenocarcinoma (≤12 cm from the anal verge) who received long-course NACRT followed by total mesorectal excision. Pelvic MRI performed 8 weeks post-NACRT assessed tumor response using the MRI tumor regression grade (mrTRG). Histopathological response was evaluated using the Rödel tumor regression grade (TRG) system. Correlation between mrTRG and pathological TRG was analyzed using Spearman’s correlation, and the diagnostic accuracy of MRI in predicting pathological complete response (pCR) was calculated.

Results: MRI demonstrated mrTRG 1–2 in 22 patients (46.8%), mrTRG 3 in 16 (34.0%), and mrTRG 4–5 in 9 (19.1%). Histopathology revealed pCR (TRG 0) in 11 patients (23.4%). MRI correctly identified 8 of 11 pCR cases. MRI prediction of pCR showed a sensitivity of 72.7%, specificity of 85.3%, positive predictive value of 61.5%, and negative predictive value of 90.3%. A significant correlation was observed between mrTRG and pathological TRG (Spearman’s r=0.64, p<0.001).

Conclusions: MRI-based assessment at 8 weeks post-NACRT demonstrates a significant correlation with histopathological response and provides reliable exclusion of complete response. Integration with clinical assessment is recommended for optimal treatment decision-making.