| Study Title:Genetic and Clinical Evaluation of Probiotic Bacillus Coagulans Strain in Patients with Irritable Bowel Syndrome: Impact on Digestive Symptoms, Protein Absorption, Metabolic rate and Immune Response Study Population:60 Patients with Irritable Bowel Syndrome Study Duration 5 Months (Treatment Duration: 3 Months [6 Visits, 1 Visit Every 2 ,Weeks]) Study Design: A randomized double-blind, placebo-controlled, parallel,multi-center, phase 3 clinical trial Inclusion Criteria: 1. Age 18 Years to 50 Years 2.Both males and females 3. Patients should fulfill Rome Foundation IBS-Diagnostic Questionnaire i.e Recurrent abdominal pain (on average, at least 1 day or week in the last 3 months) associated with two or more of the following: (Related to defecation, associated with a change in frequency of stool, Associated with a change in form of stool). 4.Patients willing to provide written informed consent and comply to protocol requirements. Exclusion Criteria: 1.Any patient with weight or appetite loss, iron deficiency anemia, fever or rectal bleeding. 2.Known inflammatory bowel disease or celiac disease patients, 3. Immuno-compromised patients. 4.Pregnancy or wishing to become pregnant during the study. 5.End-stage kidney failure on dialysis, presence of other diseases, including cancer or severe hepatic insufficiency (transaminases greater than 3.5x above normal). 6.The use of other probiotic products or antibiotics over the previous 6 months. 7.Participation in other clinical trials 8.The presence of other medical conditions that in the opinion of the investigators could jeopardize compliance with the protocol (e.g., malabsorption syndrome or an inability to take orally administered medications). Dose & Mode:Administration Need to be provided by sponsor Primary End Point:Change in the DSFQ score from baseline to Day 90 (end of study) to evaluate the efficacy of Probiotic (Bacterial)–Bacillus Coagulans Strain in improving digestive symptoms in patients with irritable bowel syndrome. Digestive Genetic Markers: •FUT2 (Fucosyltransferase 2) Gene Variations: FUT2 gene variants impact the secretion of blood group antigens into bodily fluids, including the gut. This can influence the composition of the gut microbiome and its interactions. •GCKR (Glucokinase Regulator) •Fecal microbiome & metabolites -Gastrointestinal health Standard Questionnaire : •Digestive Symptom Frequency Questionnaire (DSFQ) Enzyme Tests : •Lactase Enzyme Test •Amylase Test Bioavailability Enhancement of Protein: •Protein Digestibility-Corrected Amino Acid Score (PDCAAS): PDCAAS is a method used to evaluate protein quality by assessing the content of essential amino acids in a food or supplement. A higher PDCAAS indicates better protein bioavailability. •Amino Acid Levels: Measuring the concentration of specific amino acids in the blood can provide insights into protein absorption. Essential amino acids are of particular interest because they must be obtained from the diet. •Nitrogen - Urine analysis (Analysis total protein) •CRP- C Reactive Protein - Response to Inflammation Metabolic Study Genetic Markers: •MTHFR (Methylenetetrahydrofolate Reductase) Gene Variants: These variants can significantly impact folate metabolism, which plays a crucial role in protein synthesis and overall cellular function. •APOA1 (Apolipoprotein A1) Gene Polymorphisms: APOA1 is involved in lipoprotein metabolism and has a direct influence on protein synthesis, especially in the context of lipid transport and metabolism. •hsCRP - Metabolic Health •Lipid Profile Inflammation & Immune Response TNF-α (Tumor Necrosis Factor Alpha) Genetic Variations: TNF-α is a key cytokine involved in inflammation and immune responses. Genetic variations in this gene can modulate the immune system’s reactivity. • IL-6 (Interleukin-6) Gene Polymorphisms: IL-6 is another important cytokine that regulates inflammation and immune system function. Polymorphisms in this gene can affect immune system regulation • Immunoglobulin IgG,IgA and IgM - Level of antibiotics • Lymphocyte percentage, TLC & ALC -Immune System Cells Stress - Serum cortisol - Stress Hormone - Serum Dopamine - Memory, Movement & Etc., Standard Questionnaire: Assessments of HRQoL Functional Bowel Disorders Quality of Life (FBA) and the Functional Dyspepsia-Related Quality of Life (FDDQL). Evaluation Schedule: Baseline [Day 1]•Genetic markers associated with protein metabolism, inflammation, gut microbiome interactions, and immune response will be assessed. •Patients will complete the Digestive Symptom Frequency Questionnaire (DSFQ). •Assessments of HRQoL (FBA and FDDQL) will be conducted. •Hematological and hepatic biomarkers, fasting blood sugar level, HbA1c, and lipid profile parameters will be analyzed. •Baseline measurements of gastrointestinal symptoms, IBS severity (IBS-SSS), and stool consistency (Bristol stool form scale) will be recorded. •Vital signs and physical examination will be conducted. +Day 45 [Interim Visit]Genetic markers associated with protein metabolism, inflammation, gut microbiome interactions, and immune response will be re- assessed. Day 90 [End of Study]•Genetic markers associated with protein metabolism, inflammation, gut microbiome interactions, and immune response will be re- assessed. •Final measurements of gastrointestinal symptoms, IBS severity (IBS-SSS), and stool consistency (Bristol stool form scale) will be recorded. •Assessments of HRQoL (FBA and FDDQL) will be conducted. •Hematological and hepatic biomarkers, fasting blood sugar level, HbA1c, and lipid profile parameters will be analyzed. •Vital signs and physical examination will be conducted. •All adverse events will be reported throughout the study duration Safety Endpoints •Number of participants who Experienced at least one Adverse Event during the study duration. •Number of participants who discontinued study drug due to an Adverse Event during the study. Ethical Considerations The study will be conducted as per the National Ethical Guidelines for Biomedical and Health Research involving Human participants ICMR (2017), ICH (Step 5) ’Guidance on Good Clinical Practice’, New Drugs and Clinical Trials Rules 2019 G.S.R. 227(E) dated 19 Mar 2019, ’Good Laboratory Practice’, ‘Good Clinical Practices for Clinical Research in India’ Guidelines, Good Clinical Laboratory Practice (GCLP) and Declaration of Helsinki (Fortaleza, October 2013). |