Public disclosure of clinical trial results at Clinical Trial Registry of India- Need for transparency in research!

Introduction: Since June 15, 2009, clinical trial registration in the Clinical Trial Registry-India (CTRI) has been made mandatory by the Drugs Controller General of India to improve transparency, accountability, conform to accepted ethical standards and reporting of all relevant results of registered trials. In this study, we planned to evaluate the compliance of Indian and global sponsors with clinical trials conducted in India in terms of reporting of clinical trial results at the CTRI. Methods: We included trials registered in the CTRI between January 2018 and January 2020. The CTRI and ClinicalTrials.gov registry was thoroughly searched for all completed interventional studies. A year-wise comparative analysis was performed to evaluate the number of clinical trials reporting results in both the registry. Results: The reporting of completed interventional clinical trial results was 25/112 (22.32%) in year 2018, y, 8/105 (7.6%) in year 2019 and 17/140 (12.14%) in year 2020. There was significantly less reporting of results of Pharmaceutical company sponsored Interventional Studies-Indian at CTRI when compared with ClinicalTrials.gov registry for the year 2019 (odds ratio [OR]-0.17 (95% confidence interval [CI]: 0.08-0.36) and P < 0.0001) and year 2020 (OR-0.45 [95% CI: 0.24-0.82] and P < 0.01). The difference in results reported at CTRI was significantly low for Pharmaceutical company sponsored Interventional Studies-Global only for year 2019 (OR-0.09 [95% CI: 0.005-1.45] and P = 0.04) compared with ClinicalTrials.gov. Conclusion: There is a need to develop the culture of reporting clinical trial results in CTRI to strengthen the transparency in the research for overall benefit of public, health care professionals, and research community.

Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial.

INTRODUCTION: Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS: Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS: A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS: Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

Melanocortin Receptors: Emerging Targets for the Treatment of Pigmentation, Inflammation, Stress, Weight Disorders and Sexual Dysfunction.

Melanocortins are tiny protein molecules formed by the post-translational cleavage of proopiomelanocortin. These are bioactive peptides that are responsible for human and lower animal pigmentation patterns, energy homeostasis, and sexual function modulation. These peptides regulate numerous physiological functions by being generated in the central nervous system and peripheral tissues. Melanocortins elicit their varied biological effects by binding to a separate family of G protein, two primary proteolytic enzymes, proconvertases 1 and 2, according to recent research. These breakthroughs have opened up new avenues for research into the role of melanocortins, antagonists, and receptors in a number of physiological activities.

Evaluation of genetic polymorphism of CYP3A5 in normal healthy participants from western India - A cross-sectional study.

BACKGROUND: CYP3A5 enzymes belong to the phase I Group of drug-metabolizing enzymes, which are involved in the metabolism of 50% of the drugs. Participants with CYP3A5 genotype: CYP3A5 *1/*1 are fast metabolizers of drugs and hence will require higher dosing. Whereas those with CYP3A5 * 3/*3 are poor metabolizers of drugs and will require a lower dose to achieve target drug concentration in the blood and those with CYP3A5 * 1/*3 have intermediate drug metabolizing activity. Pharmacogenetic evaluation may improve disease outcomes by maximizing the efficacy and minimizing the toxicity of drugs in patients. MATERIALS AND METHODS: This is a single-center cross-sectional study conducted in the year 2018-2019 to study the population prevalence of genetic polymorphisms of CYP3A5 in healthy participants from western India. Eligible participants willing to give written, informed consent were enrolled in the study. Subsequently, 2 ml venous blood was collected the deoxyribonucleic acid was extracted and then stored at ‒20°C. Genotyping was done by a polymerase chain reaction and restriction fragment length polymorphism. RESULTS: A total of 400 participants with a median age of 22 years (range: 18-58 years) were included. Among them, the genotype prevalence for CYP3A5 * 1/*1 was 17% (n = 67/400); CYP3A5 * 1/*3 was 37% (n = 149/400) and that of CYP3A5 * 3/*3 was 46% (184/400). Out of the total 400 healthy participants analyzed, the allele frequency for CYP3A5 * 1 was 35% (142/400) and that of CYP3A5*3 was 65% (259/400). CONCLUSION: The genotype prevalence for CYP3A5 * 3*3 (46%) and the allele frequency for CYP3A5 * 3 (65%) respectively were the highest among the western Indian population.

A case report of Arnold Chiari type 1 malformation in acromesomelic dwarf infant.

Arnold Chiari malformation is one of the commonest cause of congenital hydrocephalus. Cause of fetal development of cerebellar tonsils remains unknown and may be diagnosed at later in life. The association of Arnold Chiari malformation with acromesomelic dwarfism is not known. We report male infant diagnosed with acromesomelic dwarfism at end of gestation period on basis of antenatal ultrasonography findings. An ultrasound scan of infant head at fifth month of birth was performed in view of increasing head circumference that revealed aqueductal stenosis with dilated posterior horn of lateral ventricles in brain.