Clinical Trial Registry Of India Research Articles

Complementary Medication for COVID-19 Outbreak Concerns in the Leprosy Community - A Passionate Proposal

Abstract: The number of COVID-19-positive cases continues to climb, causing alarm around the world. The Nilavembu (Andrographis paniculata) Kudineer of Siddha medicine, an alternative medicine practiced in India, has already been shown to be beneficial in viral outbreaks like Chikungunya and Dengue fever. Several investigations have demonstrated that these herbs have anti-inflammatory, analgesic, antipyretic, antibacterial, and antiviral activities against the Herpes simplex virus and Ebstein Barr virus. This herbal remedy has also been shown to have a low risk of negative side effects. There is currently no approved pharmaceutical treatment for COVID-19. Using the phrases 'COVID-19,' 'Ayush,' 'Siddha,' and 'Leprosy,' we searched other databases such as Google, Embase, ScienceDirect, and the Clinical Trial Registry of India. In another research on Siddha treatment, Kabasura Kudineer, a decoction of 15 herbal items was discovered to have activity against the spike protein of SARS COV-2 using an in-silico compound method. As there are no effective treatments available for the prevention and treatment of mild to moderate cases, these two medicines, Nilavembu Kudineer, and Kabasura Kudineer can be used as part of a COVID-19 prophylaxis using a combination of modern and alternative medicine.

Effects of pain education on disability, pain, quality of life, and self-efficacy in chronic low back pain: A randomized controlled trial.

Low back pain stands as a prevalent contributor to pain-related disability on a global scale. In addressing chronic low back pain (CLBP), there is a growing emphasis on incorporating psychological strategies into the management process. Among these, pain education interventions strive to reshape pain beliefs and mitigate the perceived threat of pain. This randomized controlled trial sought to assess the effects of pain education on various aspects, including pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals grappling with CLBP. The clinical trial, retrospectively registered with the Clinical Trials Registry of India (CTRI/2021/08/035963), employed a two-arm parallel randomized design. Ninety-two participants with CLBP were randomly assigned to either the standard physiotherapy care with a pain education program or the control group. Both groups underwent a 6-week intervention. Assessment of pain intensity (using NPRS), disability (using RMDQ), self-efficacy (using the general self-efficacy scale), and well-being (using WHO 5I) occurred both before and after the 6-week study intervention. Post-intervention score comparisons between the groups revealed that the pain education intervention led to a significant reduction in disability compared to the usual standard care at 6 weeks (mean difference 8.2, p < 0.001, effect size Cohen d = 0.75), a decrease in pain intensity (mean difference 3.5, p < 0.001, effect size Cohen d = 0.82), and an improvement in the well-being index (mean difference 13.7, p < 0.001, effect size Cohen d = 0.58). The findings suggest that integrating a pain education program enhances the therapeutic benefits of standard physiotherapy care for individuals dealing with chronic LBP. In conclusion, the clinical benefits of pain education become apparent when delivered in conjunction with standard care physiotherapy during the management of chronic low back pain.

RETRACTION: Comparative effectiveness of low-level laser therapy and transcutaneous electrical nerve stimulation in symptomatic Temporomandibular Disorders: A Randomised Control Trial.

Batra, S. Srivastava, A., Shivakumar, G. C., Marrapodi, M. M., Herford, A. S., Cicciù, M., Minervini, G. (2023) Comparative effectiveness of low-level laser therapy and transcutaneous electrical nerve stimulation in symptomatic Temporomandibular Disorders: A Randomised Control Trial. Journal of Oral Rehabilitation, 50: 1185-1193. https://doi.org/10.1111/joor.13555 The above article, published online on 05 July 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Peter Svensson, and John Wiley and Sons Ltd. The retraction has been agreed following concerns raised by a third party about the ethical approval for the study described. The publisher contacted the authors, who provided a letter of ethical approval from People's College of Dental Sciences & Research Center, People's University, which did not match the ethical approval reported in the article. The authors reported that the study was initiated at Banaras Hindu University, but were not able to provide evidence of ethical approval from this institution. In addition, the authors did not provide an explanation for why the clinical trial was registered with Clinical Trial Registry-India retrospectively, which violates the journal's author guidelines that require authors to provide an explanation for retrospective registration of clinical trials. Following the investigation by the publisher, the journal has concluded this article did not follow the journal's requirements regarding ethical approval of clinical trials and registration of clinical trials, and so the journal must issue a retraction. Shivakumar, G. C. has stated that Marrapodi, M. M., Herford, A. S., Cicciù, M., and Minervini, G. were not involved in the investigation, data curation, conceptualization, methodology, or formal analysis of the clinical study. The authors disagree with this retraction.

Intravenous versus oral ‘l-ornithine-l-aspartate’ in overt hepatic encephalopathy: a randomized comparative study

Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. In this RCT, we compared the efficacy of intravenous (IV) l-ornithine-l-aspartate(LOLA) versus Oral LOLA in patients with chronic liver disease(CLD) enduring overt Hepatic Encephalopathy(OHE). 40 CLD patients with OHE were randomly assigned IV or oral LOLA in a 1:1 ratio. Patients were graded for HE and monitored for serum ammonia levels from day 1 to day 5. The aim was to compare IV versus oral LOLA efficacy in HE grades improvement and its correlation with ammonia levels. The study was registered with clinical trials registry-India, CTRI/2020/12/029943. Baseline characteristics of patients in both groups were similar. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511). Significant reductions in ammonia levels were observed from day 1 to day 5 within each group (p < 0.001). HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn’s Disease

BackgroundPerianal fistulas (PF) affect one-third patients with Crohn’s disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population.MethodsAn open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn’s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.ResultsTen patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time.ConclusionsAllogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing.Trial registrationThe study was prospectively registered on Clinical trials registry – India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in.

Quality of Life in Patients Undergoing Endoscopic Thyroidectomy Versus Conventional Open Thyroidectomy: Interim Results From Randomized Trial.

We determined whether endoscopic thyroidectomy (ET) is associated with better health-related quality of life (QoL) compared with open thyroidectomy. We randomly assigned 28 patients aged older than 18 years, Bethesda IV or less on cytology and gland volume of <40 mL to undergo hemithyroidectomy through either open or endoscopic (axillo-breast approach/bilateral axillo-breast approach) technique. The primary outcome was QoL scores on the Short Form-36 and Thyroid-Specific Questionnaire at 2, 6, and 12 weeks postsurgery. Secondary outcomes were postoperative complications, hospital stay, and pain scores. The generic QoL scores based on Short Form-36 were statistically nonsignificant between the two groups. QoL scores based on Thyroid-Specific Questionnaire were statistically significant (P < 0.05) favoring open thyroidectomy in the following domains: (1) numbness at 2, 6, and 12 weeks (P = 0.04, 0.004, and 0.005, respectively), (2) shoulder impairment at 2 weeks (P = 0.017), and (3) favoring ET in cosmesis at 6 and 12 weeks (P = 0.037 and 0.02, respectively). ET has longer operative time (104.6 ± 25.4 vs 123 ± 8.9 min; P = 0.03), longer hospital stays (2.8 ± 0.4 vs 2.4 ± 0.5; P = 0.056) and higher pain scores at 2 and 6 weeks (P = 0.007 and 0.012, respectively) but decreased intraoperative bleeding (33.5 ± 6.4 vs 29.1 ± 3.7 mL; P = 0.037). ET has higher cosmetic satisfaction, increased numbness, and shoulder movement impairment during short-term postsurgery follow-up. Both techniques are similar in impacting general physical, mental, and social health-related QoL. (Clinical Trials Registry of India, Reg. No. CTRI/2020/07/026374).

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. Clinical Trials Registry-India (CTRI/2020/08/027000).

Role of prophylactic tranexamic acid in reducing blood loss during cesarean section: A double-blind placebo-controlled randomized controlled trial

ABSTRACT Background: Postpartum hemorrhage (PPH) is defined by the World Health Organization as blood loss of ≥500 mL within 24 h of delivery. Globally, hemorrhage accounts for 27.1% of maternal deaths, making it the leading direct cause of maternal death. PPH has been identified in more than two-thirds of reported hemorrhage-related deaths, causing 38% of maternal deaths in India. Tranexamic acid, an antifibrinolytic, has been used to control bleeding after PPH is identified. Materials and Methods: Antenatal women admitted for elective cesarean section were randomized into two arms: the case group (received one gram of tranexamic acid 20 min prior to skin incision) and the control group (received a placebo), each group consisting of 36 participants. Clinical Trials Registry – India (CTRI) registration number – CTRI/2021/02/031579. Results: The mean (±standard deviation [SD]) intraoperative blood loss in the case group was 241.25 (±67.83) mL, and in the control group, it was 344.92 (±146.67) mL (P = 0.001), while postoperative blood loss did not differ significantly between the groups (P = 0.1470). In terms of the difference in hemoglobin, there was a significant difference between the two groups (P = 0.001). No significant maternal or neonatal side effects were found. Conclusion: Preoperative tranexamic acid, when given in elective cesarean section, significantly reduces intraoperative blood loss.

Role of preoperative zinc, magnesium and budesonide gargles in Postoperative Sore Throat (POST) - a randomised control trial.

Post-operative sore throat (POST) has an incidence ranging from 21 to 80%. To prevent the development of POST, several pharmacological measures have been tried. Aim of this study was to compare the efficacy of preoperative zinc, magnesium and budesonide gargles in reducing the incidence and severity of POST in patients who underwent endotracheal intubation for elective surgeries. We conducted a prospective, randomized, double-blind, controlled equivalence trial in 180 patients admitted for elective surgical procedures under general anaesthesia. Patients were randomised into three groups; group Z received 40mg Zinc, group M received 250mg Magnesium Sulphate and group B received 200µg Budesonide in the form of 30ml tasteless and colourless gargle solutions. Sore throat assessment and haemodynamic recording was done postoperatively at immediate recovery (0h) and 2, 4, 6, 8, 12 and 24h post-operatively. POST was graded on a four-point scale (0-3). POST score was comparable at all recorded time points i.e. 0,2,4,6,8,12 and 24h. Maximum incidence was seen at 8h in group B (33.3%) and the minimum incidence was at 24h in group Z (10%) (p > 0.05). It was found that the incidence of POST was more in the surgeries lasting longer than 2h in all groups. This difference was found to be statistically significant in Groups M and B. The incidence of POST was found to be comparable between laparoscopic and open procedures. Magnesium, zinc and budesonide have an equivocal effect in the prevention of POST at different time points. The incidence of sore throat increases significantly in surgeries lasting more than two hours if magnesium or budesonide have been used as premedicant. Duration of surgery is an independent predictor for POST. CTRI/2021/05/033741 Date-24/05/2021(Clinical Trial Registry of India).

Comparison of the Outcomes of Enhanced Recovery After Surgery and Traditional Recovery Pathway in Robotic Hysterectomy for Benign Indications: A Randomized Controlled Trial

ObjectiveThe present study aimed to evaluate the impact of implementation of the ERAS program in patients undergoing robotic hysterectomy for benign indications in comparison with conventional management DesignRandomized controlled trial SettingNorth Indian tertiary care hospital ParticipantsPatients aged 40-60 years willing to sign the informed written consent were included while cases with contraindications for neuraxial anesthesia were excluded. 130 subjects undergoing robotic hysterectomy, divided into ERAS (N=65) and conventional (non-ERAS) (N=65) groups. InterventionsComponents of the ERAS protocol included preoperative counselling, carbohydrate loading, early removal of catheter, and early ambulation. Both groups underwent optimization of medical conditions, standardized anesthesia, and venous thromboembolism prophylaxis. ResultsOutcome measures included length of hospital stay (LOHS), time to tolerance of diet, postoperative complications, readmission rates, and quality of life assessed by WHO-QOL BREF. Baseline characteristics were comparable between groups. ERAS group showed significantly lower docking time (4.82±0.73 versus 5.31±0.92 minutes), faster tolerance of diet (0.14±0.35 versus 1.14±0.35 days), and earlier resumption of ambulation (0.42±0.5 versus 1.26±0.44 days). Time for 'fit for discharge' (1.43±0.61 versus 2.97±1.1 days) and LOHS (2.85±1.09 versus 3.78±1.29 days) were significantly lower in the ERAS group. Postoperative complications and readmission rates were comparable. Quality of life scores favoured the ERAS group at postoperative day 1 and 30. ConclusionThe combination of ERAS and robotic surgery improves patient outcomes, shortens hospital stay, and enhances postoperative recovery without increasing complications. This research serves as a pioneering effort in assessing ERAS impact on robotic hysterectomy for benign indications, providing valuable insights for future multicentric studies and supporting the integration of ERAS protocols to enhance patient outcomes and quality of life.Clinical trial registration: Clinical trial registry of India: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NjczODM=&Enc=&userName=)

A parallel-arm randomised control trial to study the effects of risk communication methods for prevention of cardiovascular diseases: EFFRICO trial

ABSTRACT Introduction: Cardiovascular diseases (CVDs) have many risk factors; few can be modified through health education. Traditional patient counselling methods fail to impact health behaviours to prevent or reduce the risk of CVDs. Objectives: This study was conducted to estimate the effect of various risk communication methods on CVD risk reduction and medication adherence. Design: An open-label superiority randomised control trial was conducted where 159 patients were randomised into three groups: Communication of 10-year Framingham CVD risk score, heart age, and routine care. Follow-up was done 3 months after recruitment. The primary outcome was a difference in excess 10-year Framingham CVD risk score in the end-line compared to baseline. The status of modifiable behavioural risk factors at baseline was expressed as ‘yes’ and ‘no’, and follow-up was defined as ‘action’, ‘positive maintenance’, ‘negative maintenance’, and ‘defaulter’. The trial was registered with the Clinical Trials Registry India (CTRI NO. CTRI/2020/10/028614). Setting: The study setting was screening outpatient department (OPD), General Medicine OPD, and Cardiology OPD of a tertiary care hospital in Central India. Participants: Participants aged &gt;30 years, residing in Bhopal for more than 6 months, diagnosed with hypertension or diabetes mellitus or both, and having any of the four CVD behavioural risk factors: tobacco use, alcohol use, physical inactivity, or unhealthy diet. Results: Median excess 10-year Framingham CVD risk scores were 0.945% (CI: 1.275–4.297), –0.850% (–3.932–2.075), and –1.300% (–5.100–0.900) (10-year Framingham CVD risk score vs Heart age vs Routine care) and 0.000% (–3.125–5.925), –1.600% (–3.760–1.475), and –1.400% (–6.600–5.900) before and after intervention, respectively (P &gt; 0.05). Positive maintenance was higher in both intervention groups concerning all modifiable behaviours, with a higher proportion reported in the 10-year Framingham risk score. The action phase was reported higher in intervention groups for medication adherence, addiction, and dietary changes. Conclusion: Systematic risk communication methods reduced the probability of contracting CVD in the future, though this finding was statistically insignificant.

MRI based evaluation of carcinoma gallbladder using apparent diffusion coefficient (ADC) and diffusion weighted imaging (DWI)

Background Carcinoma of the gallbladder is a malignant neoplasm, which is associated with a poor prognosis due to its often-asymptomatic nature and late-stage diagnosis. Non-invasive imaging techniques play a key role in the early detection and characterization of gallbladder carcinoma. This thesis presents a comprehensive analysis of the utility of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping in the magnetic resonance imaging (MRI) evaluation of carcinoma of the gallbladder. The primary objective of this research was to investigate the exact diagnostic accuracy and potential clinical applications of DWI and ADC in assessing carcinoma of the gallbladder and related tumour aggressiveness. A systematic review of existing literature was conducted to establish a foundation for this study with efforts to acquire relevant imaging data. The results of this study demonstrate the efficacy of DWI and ADC in the detection of carcinoma of the gallbladder when compared to conventional MRI sequences. These advanced imaging techniques hold promise in increasing the accuracy of diagnosis, ultimately leading to improved patient outcomes and more informed clinical decision making. The potential of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping in the evaluation of gallbladder cancer using magnetic resonance imaging (MRI) is thoroughly analysed in this thesis. Methods A descriptive prospective study will be done at Acharya Vinoba Bhave Rural Hospital, Sawangi, involving 20 patients with clinically suspected carcinoma gallbladder, who are referred to the department of Radiodiagnosis. These patients will be subjected to study-purposive sampling. Conclusion After an appropriate statistical analysis, we expect to assess the role of Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) mapping in the magnetic resonance imaging (MRI) evaluation of carcinoma of the gallbladder. CTRI registration This trial has been submitted to Clinical Trials Registry-India (CTRI) for Review. Registration Number: REF/2023/09/072780 Registration date:01/05/2023 URL of trial: https://www.ctri.nic.in/

Effect of high dietary fiber intake on insulin resistance, body composition and weight, among overweight or obese middle-aged women: study protocol for a double-blinded randomized controlled trail.

Background Obesity is a major consequence of malnutrition and significantly contributes to the global burden of chronic diseases. Currently, there are more overweight and obese individuals than underweight individuals. Increased fiber intake can increase insulin sensitivity and fat oxidation. According to research studies, the average dietary fiber consumption is below the recommended value, and the WHO anticipates that the worldwide obesity prevalence has increased in the past ten years. Aim To evaluate the effect of high dietary fiber intake on insulin resistance, body composition, and weight in overweight and obese middle-aged women. Method This hospital-based study evaluated 500 people during phase 1 to identify the prevalence of insulin resistance among overweight and obese middle-aged women. An RCT with intervention and control arms for 180 individuals is being conducted in Phase 2 to determine the effect of increased dietary fiber consumption on insulin resistance, body composition, and weight in overweight or obese middle-aged women. In the intervention group, women were counselled for 15 min and given a tailored food chart including 40 g of fiber. Women in the control arm will receive a typical food care plan with 25 g of fiber, based on their health status. Each engaged woman received fiber nutritional empowerment. Discussion Increasing dietary fiber consumption can improve insulin resistance, body composition, and weight in middle-aged overweight and obese women. Trial registration The Clinical Trials Registry of India (CTRI/2022/01/039074) has registered this study as a clinical trial on January 3, 2022 http://ctri.nic.in

A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy.

The majority of mainstream antidepressants lack the promise of complete amelioration of symptoms. Other pitfalls include the latency period and side effects. These issues prompted investigations concerning thevarious roles of serotonin (5-HT) neurotransmissions in the etiology of depression. In this study, each study participant received vilazodone, vortioxetine, and escitalopram monotherapy for major depressive disorder (MDD)for 16 weeks. After that, the subject's scores on the Hamilton Depression Rating Scale (HDRS)-17 item version and the Montgomery Åsberg Depression Rating Scale (MADRS) were evaluated. In the study population, we kept track of the incidence of adverse events. Ninety-six patients with MDD participated in this open-label, randomized, three-arm study. Participants were allotted into three groups according to a 1:1:1 ratio and given vilazodone (20-40 mg/day), vortioxetine (5-20 mg/day), or escitalopram (10-20 mg/day) for 16 weeks. Vortioxetine and vilazodone are test medications, with escitalopram serving as the control. After the baseline visit, follow-up appointments were scheduled every four weeks. Per-protocol (PP) and intent-to-treat (ITT) populations served as means for efficacy and safety evaluations, respectively. We prospectively registered this research in the Clinical Trial Registry, India (CTRI) (2022/07/043808). Out of the 134 patients we screened, 109 (81.34%) were eligible. Ninety-six (88.07%) of them completed the 16-week trial. In the PP population (n = 96), we analyzed efficacy. They had a mean age of 46.3 ± 6.2 years. At baseline, each group's median HDRS score was 30.0 (p = 0.964). Following 16 weeks of antidepressant therapy, these scores dropped to 15.0, 14.0, and 13.0 (p = 0.002). Baseline MADRS scores for all groups were 36.0 (p = 0.741). They had corresponding values of 20.0, 18.0, and 17.0 at 16 weeks (p < 0.001). Regarding both efficacy endpoints, the post-hoc analysis with the Bonferroni correction demonstrated statistically significant differences (p < 0.001). We performed the safety assessments within our ITT population (n = 109). Ninety-six adverse events were recorded. Nonetheless, none of them seemed serious. Still, five participants opted out because of their side effects. Vomiting and nausea were the most frequent side effects. Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further.

Effects of Withania somnifera Extract in Chronically Stressed Adults: A Randomized Controlled Trial.

Stress is a known causative factor in modulating cognitive health, which overall well-being and quality of life are dependent on. Long-term stress has been shown to disrupt the balance of the hypothalamic-pituitary-adrenal (HPA) axis. Adaptogens, such as Withania somnifera (ashwagandha), are commonly used in Ayurvedic medicine for stress relief and ameliorating HPA-axis dysfunction. The aim of this study was to support the role of a root and leaf water-extracted ashwagandha extract (WS) in stress reduction by confirming the lowest clinically validated dose for stress management (125 mg/day) in a dose-dependent clinical study in adults with self-reported high stress. An 8-week, randomized, double-blinded, placebo-controlled study to compare the effects of three different WS extract doses (125, 250 and 500 mg) was performed. A total of 131 adults were enrolled, and 98 were included in the final analysis. Attenuation of chronic stress was measured using the 14-item Perceived Stress Scale (PSS) and biochemical-related stress parameters. We have shown that aqueous WS extract (roots and leaves) safely reduces mild to moderate chronic stress at doses of 125 mg, 250 mg, and 500 mg/day for 8 weeks. Our findings demonstrate the stress-reduction capabilities of this well-characterized aqueous extract of WS (root and leaf) at the low dose of 125 mg/day, in a dose-dependent manner, via the modulation of the HPA axis. This study was registered with the Clinical Trials Registry-India (CTRI) with the registration number: CTRI/2019/11/022100.

Improving walking via real-time visual feedback after stroke in treadmill training (RE-VISIT): a protocol for randomized controlled trial

BACKGROUND: After a stroke, most patients often suffer reduced walking ability and balance. Restoring walking ability and improving balance are major goals of stroke rehabilitation. Treadmills are often used in clinical setups to achieve these goals. Adding dimensions to the visual feedback in addition to the mirror for real-time frontal view is proven to enhance the gait. It is, therefore, important to design additional real-time visual feedback in treadmill training, in particular for the sagittal view involved side. OBJECTIVE: The objective of this study is to test if the real-time sagittal visual feedback during treadmill training is superior to the conventional mirror feedback treadmill training program of equivalent intensity in improving walking speed and balance after stroke. METHODS/DESIGN: The RE-VISIT trial (Real-time Visual feedback after Stroke in Treadmill training) is registered in the Clinical Trial Registry of India (CTRI/2023/10/058299). In this two-arm randomized control trial, which will be a single-blinded study, 42 eligible stroke survivors undergoing rehabilitation will be randomly allocated (1:1 ratio) to either real-time visual sagittal feedback along with front mirror (experimental) group or only front mirror treadmill training (control) group, all the participants will receive 15 sessions of treadmill training for up to 15 min at a safe self-selected speed over 5-6 weeks. The RE-VISIT (experimental) group will receive real-time, visual sagittal view feedback of the involved lower limb trajectory along with the routine front mirror view during treadmill training and will be asked to modify their gait pattern. The control group will receive treadmill walking training only with the routine front mirror view feedback. Clinical and gait assessments will be conducted at the baseline, immediately following the final session of training, and at the 9th week during follow-up. The outcome measures of interest are walking speed (primary) and balance (secondary), which will be measured prior to baseline, post 15 sessions of training, and at the 9th week following training. DISCUSSION: This REVISIT trial will provide insight and contribute to the existing innovation and modifications of incorporating real-time visual feedback during treadmill training in post-stroke gait rehabilitation. The findings will help the better designing of a gait rehabilitation program with a treadmill for post-stroke subjects to improve walking speed, and balance for those who have greater difficulties in community ambulation. We anticipate that those in the REVISIT training will demonstrate improved walking ability.

A randomized controlled trial of medication adherence and management of risk factors for secondary prevention of stroke (MaMoRS) using a smartphone-based application.

There are little data on the use of smartphone-based applications for medication adherence and risk-factor control for the secondary prevention of stroke in low-and-middle-income countries (LMICs). The aim was to determine whether a smartphone-based app improved medication adherence, risk-factor control, and provided health education to stroke survivors for lifestyle and behavioral modifications. An unblinded, single-center randomized controlled double arm trial with 1:1 allocation among stroke survivors was performed in South India. The primary outcome was medication adherence, with co-primary outcomes of lifestyle and behavioral factors and control of vascular risk factors, at 3 and 6 months. Among 351 stroke survivors screened, 209 were recruited. The mean (standard deviation (SD)) age of the intervention (n = 105) group was 60 (12) years and that of the control (n = 104) group was 60 (10) years. In the primary outcome, mean medication adherence significantly improved in the intervention group with a between group difference of 0.735 (95% confidence interval (CI) = 0.419 to 1.050), p < 0.001. Being in intervention group (OR = 4.5; 95% CI = 2.3 to 8.9), stroke recurrence (OR = 3.3 (95% CI = 1.9 to 7.8)), and regular physician visits (OR = 2.1; 95% CI = 1.0 to 4.4) were significant predictors of good medication adherence. Considering the co-primary outcomes, compared to the control group, participants in the intervention group had a greater improvement in self-reported healthy diet intake (p = 0.003), intake of fruits (p = 0.005), and were physically more active (p = 0.001). At 6 months, mean fasting blood sugar (p = 0.005) and high-density lipoprotein cholesterol higher (p = 0.024) in the intervention group. The use of a mobile app is an effective method to improve medication adherence and risk-factor control in stroke survivors and is feasible in LMICs like India. Data used during the study are available from the corresponding author on request. The study is registered in Clinical Trial Registry of India (CTRI/2022/06/042980).

An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial

Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (P < 0.0001) and GEMCOVAC-19 (P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (P < 0.0001), but not in the ChAdOx1 nCoV-19 arm (P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475.

Immunogenicity and safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14™) administered to 6–8 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study

BackgroundIntroduction of pneumococcal conjugate vaccines (PCVs) reduced the number of cases of pneumococcal disease (PD). However, there is an increase in clinical and economic burden of PD from serotypes that are not part of the existing pneumococcal vaccines, particularly impacting pediatric and elder population. In addition, the regions where the PCV is not available, the disease burden remains high. In this study, immunogenicity and safety of the BE’s 14-valent PCV (PNEUBEVAX 14™; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) was evaluated in infants in comparison to licensed vaccine, Prevenar-13 (PCV-13). MethodsThis is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6–8 weeks old healthy infants at 6–10–14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs), and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS (anti-pneumococcal capsular polysaccharide) IgG concentration and functional antibody titers through opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study. FindingsThe safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature. No severe or serious AEs were reported in both the treatment groups. For the twelve common serotypes and for the additional serotypes (22F and 33F) in BE-PCV-14, NI criteria was demonstrated as defined by WHO TRS-977. Primary immunogenicity endpoint was met in terms of IgG immune responses for all 14 serotypesof BE-PCV-14. Moreover, a significant proportion of subjects (69%) seroconverted against serotype 6A, even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes common to PCV-13. InterpretationsBE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. It also elicited cross protective immune response against serotype 6B.These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine.The study was prospectively registered with clinical trial registry of India – CTRI/2020/02/023129.

Diclofenac Transdermal Patch versus Oral Diclofenac on Post Endodontic Pain and Quality of Life- A Randomised Clinical Trial.

To compare the effect of pre-treatment transdermal and oral diclofenac on post-endodontic pain level and oral health-related quality of life (OHRQOL) in patients with symptomatic irreversible pulpitis with apical periodontitis in mandibular molars following single visit root canal treatment. This parallel-arm, randomised, double-blinded clinical trial is reported according to the Consoli-dated Standards of Reporting Trials (CONSORT) 2020 guidelines. The protocol was approved by the Institu-tional Ethical Committee on 30th March 2021 (MADC/IEC-I/029/2021) and registered at the clinical trial reg-istry of India (CTRI/2021/12/038696). Adult patients fulfilling the eligibility criteria were randomised into two groups. Group DTP received a diclofenac transdermal patch 100 mg, and Group DOT received a diclofenac oral tablet 100 mg one hour before root canal treatment. Pain scores were checked at baseline, 2, 4, 6, 8, 24, 48, and 72 hours after the treatment. OHRQOL was assessed at baseline and one week after the treatment. Both groups were associated with a significantly lower incidence of post-operative pain and im-proved OHRQOL. At 2 hours, the pain level was significantly lower with an oral diclofenac tablet, and at 24 hours, the pain level was significantly lower with a diclofenac transdermal patch. Regarding OHRQOL, there was no significant difference between the two groups. Within the limitations of this study, the diclofenac transdermal patch had lesser post-operative pain at 24 hours, whereas the oral diclofenac tablet had lesser pain at 2 hours.