Efficacy and Safety of Bacillus coagulans LBSC in Drug Induced Constipation Associated With Functional Gastrointestinal Disorder: A Double-Blind, Randomized, Interventional, Parallel, Controlled Trial a Clinical Study on Bacillus coagulans LBSC for Drug Induced Constipation Associated With FGIDs.

ABSTRACT

Background: Active drugs and nutraceutical supplements commonly induce various gastrointestinal illnesses, and constipation is a major gastrointestinal symptom accompanied with functional gastrointestinal disorders. Drug-induced imbalance in gut microbiota may play critical role in such physiological disturbances. Probiotics have been known for resuming normal and healthy gut microbiome. Objective: To investigate the clinical efficacy and safety of Bacillus coagulans LBSC in the treatment of drug induced constipation associated with functional gastrointestinal disorder (FGID) symptoms. Methods: A prospective, interventional, randomized, double-blind, parallel, multi-arm, controlled trial with 168 patients experiencing drug induced constipation associated with FGID symptoms (DICAWFGID) screened through Rome IV criteria were randomized into 2 arms, i.e. placebo arm (n = 28) and atorvastatin, atenolol, metformin, amitriptyline, and calcium in test arm (n = 28/arm). Patients in both arms received similar dosages (1 g sachet, 3 times a day) for 35 days. The occurrence of constipation using Bristol Stool Form Scale, assessment of degree of constipation on 4-point Likert scale, occurrence of hard stool and degree of stool expulsion on 3-point scale, and defecation frequency were primary endpoints. While, secondary outcomes consisted of the changes in severity of FGID symptoms, visual analogue scale and tolerance to IP, along with reports of adverse events (AEs) and severe adverse events (SAEs). Results: There was a significant reduction in occurrence of constipation (≥98.6% and P-value <0.05) in test arm over the placebo arm. Assessment of co-primary endpoints showed significant improvements in degree of stool consistency (P-value 0.0232; CI 0.1870, 1.1629), borderline significantly superior in degree of stool expulsion (P-value 0.0553; CI 0.0378, -0.4939), while the other co-primary efficacy endpoints displayed considerably improved advancement (non-significant, P-value ≥0.05). The intra group analysis of symptoms at start of treatment (SOT) and end of treatment (EOT) revealed a significant reduction in scores for occurrence of constipation and degree of constipation, whereas significant improvement in the scores for degree of stool consistency and degree of stool expulsion (P-value <0.001) after the intervention period. In secondary endpoints, the processed responses clearly signified a considerable positive improvement (non-significant, P-value ≥0.05) in other symptoms of constipation associated with FGIDs as determined by the changes in the EOT-SOT score. The study data also highlighted the safety of Bacillus coagulans LBSC at the studied dose. No AEs and/or SAEs were documented during the investigation. Conclusion: At the studied dose, Bacillus coagulans LBSC was safe for oral consumption and effective in the management of the drug induced constipation associated with FGIDs symptoms.