A clinical trial to study the effects of Bacillus subtilis strain PB6, as add-on to standard maintenance therapy in the treatment of mild to moderate ulcerative colitis

Phase 2

• Conditions: Mild to Moderate Ulcerative Colitis

• Registration Number: CTRI/2009/091/000693
• Lead Sponsor: Kemin Pharmaa division of Kemin Industries South Asia Pvt. Ltd.The Trapezium, No 39, Nelson Manickam Road, Chennai-600029, India

Brief Summary

This is a multi-center, randomized, double-blind, placebo-controlled study of two dosages of Bacillus subtilis strain PB6 for add-on treatment of mild to moderate active ulcerative colitis. A total of 180 patients will be randomized in three treatment arms (60 patients in each arm) and the trial duration will be 9 weeks (1 week screening/run-in+8 weeks treatment period). The primary objective of the trial is to assess the efficacy of Bacillus subtilis strain PB6 in subjects with a flare-up of mild to moderate active UC while subjects are on their usual maintenance treatment with mesalazine/sulfasalazine. The primary outcome measure will be the proportion of patients in remission i.e. UCDAI score equal to or less than < 2 with no individual subscore >1. The secondary objectives are to determine the effective dose of Bacillus subtilis strain PB6 for induction of remission, to assess the tolerability of the two different doses of Bacillus subtilis strain PB6, to assess the quality of life by an appropriate questionnaire (IBDQ) and to ascertain the nutritional value of Bacillus subtilis strain PB6 in UC subjects.

Detailed Description

Not available

Recruitment & Eligibility

• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

• Must sign and date written informed consent prior to any study-related procedures and, in the opinion of the investigator, be willing and likely to comply with all requirements of the study2.
• Male or non-pregnant female patients 18-65 years of age, inclusive3.
• A history of UC for at least 6 months prior to time of screening4.
• All subjects must have clinical and endoscopic confirmed diagnosis of active mild to moderate UC with disease extension beyond the rectum (>12 cm from the ano-rectal junction)?confirmed by obligatory colonoscopy/endoscopy at screening: full report to be available and score equal to or greater than 2 (at least moderate friability)?Ulcerative Colitis Disease Activity Index [UCDAI] of 5-10, inclusive, as assessed on screening (based on retrospective recall by the subject over the previous 3 days) and confirmed after 7 days of baseline observation, before inclusion in the randomization procedure, and not improving more than 2 score points during this run-in period5.
• Duration of current relapse < 6 weeks from screening (according to patient)6.
• Oral mesalazine/sulfasalazine maintenance therapy (eqaul to or less than 2 g/day) for no less than 30 days prior to screening.7. Females of childbearing potential require a negative urine pregnancy test and must agree to abstinence or to use prescription contraceptives and to use a barrier contraceptive device along with a spermicidal product for the duration of the study.
• Subjects who are surgically sterile, menopausal or using contraceptive implants prior to the study enrolment are not required to utilize dual contraceptive techniques8.
• Otherwise in general good health as judged by the investigator.

Exclusion Criteria

• Proctitis (equal to or less than 12 cm from the ano-rectal junction)2.
• Indeterminate colitis3.
• Crohn's disease4.
• Previous colonic surgery5.
• Severe or fulminant UC [UCDAI >10] or requiring hospitalization6.
• Evidence of other forms of inflammatory bowel disease7.
• Subjects with a new diagnosis of UC8.
• Subjects who altered their mesalazine/sulfasalazine dosage (dose regimen or dose) in the previous 2 weeks before screening9.
• Subjects with a positive stool culture for any enteric pathogens that is clinically significant, pathogenic ova or parasites, or a positive enzyme immunoassay (EIA) that is subsequently confirmed by a positive cytotoxin assay for C.
• difficile toxin10.
• Subjects who have used the following medications within the specified period-Loperamide and other anti-diarrheal agents, probiotics, antibiotics: 1 week wash-out during baseline period-Non steroidal anti-inflammatory drugs (NSAIDs) and Cyclo-oxygenase-2 (COX-2) inhibitors, within 14 days from screening-Oral and injectable steroids, within 30 days from screening-Rectally administered mesalazine/sulfasalazine or other 5-ASAs or steroids, within 7 days from screening.
• Topical dermatological corticosteroids are not excluded-Antivirals or antifungals within 30 days-Immunomodulating/suppressing drugs or biologicals (including anti TNF-α, cyclosporine, thalidomide, methotrexate) within 2 month-Sulfasalazine or mesalazine at higher dose than for maintenance treatment (higher than 2g/day)11.
• Failing to respond to steroids within the previous year prior to screening12.
• Subjects who have any other clinically significant disease(s) which, in the opinion of the investigator, could compromise the subject?s involvement in the study or overall interpretation of the data, such as mental/emotional disorder, dysplasia or cancer, HIV, uncontrolled hematologic, renal, hepatic, metabolic pulmonary or cardiovascular disease, active alcohol or drug abuse13.
• Needing enemas to treat their disease or to maintain remission14.
• Subjects with abnormal laboratory values at admission which are clinically significant by the investigator (outlier values outside the normal values are allowed and to be marked as ?NCS?
• if considered Non-Clinically Significant (NCS) by the investigator based on the nature of the disease, quite some UC patients having an aberrant immune response and abnormal laboratory values due to the impaired absorption, and blood loss)15.
• Subjects whose UCDAI score decreases ≥2 during the 7-day run-in period16.
• Allergy to aspirin or salicylate derivatives17.
• Subject with a history of drug allergy in general or hypersensitivity to probiotics18.
• Participation in another clinical study within the 3 months prior to screening19.
• Inability to comply with the protocol requirements or to fill in the diary cards20.
• Pregnancy or breast-feeding women or women of child-bearing potential not agreeing to birth control.

Study & Design

• Study Type: Not specified
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of patients in remission i.e. UCDAI score equal to or less than 2 with no individual subscore >1	At endpoint for ITT population and week 8 (visit 3) for PP population

Secondary Outcome Measures

Name	Time	Method
UCDAI Score -Change from baseline (week 0, visit 0)	Week 8
Proportion of patients in Remission: UCDAI score ≤1 [stool frequency normal, rectal bleeding absent and a colonoscopy/endoscopy score reduction of 1 point or more from baseline]	Week 8 and end of treatment
UCDAI Score -Change from baseline (week 0, visit 0) in partial UCDAI score	Week 2, 4 and 8
Proportion of patients in: Complete remission: UCDAI score = 0 [=normal stool frequency, no rectal bleeding and a normal or quiescent appearance of mucosa on colonoscopy/endoscopy]	Week 8 and end of treatment
Proportion of patients in Colonoscopic/endoscopic remission: defined as UCDAI endoscopy score of ≤1	Week 8 and end of treatment
Proportion of patients in: Clinical remission (cessation of bleeding and normal stool frequency, scores of 0 for both symptoms)	Week 2, 4 and 8
Pilot HNPQ (patient rating) plus potentially objective parameters (maintenance of weight, hemoglobin)	Week 4 and 8
Safety: Tolerability score	2, 4 and 8 weeks
Clinical Response - proportion of patients with: -Overall improvement, defined as a decrease in UCDAI ≥3 from baseline [stool frequency, rectal bleeding, Physicians rating of disease activity and colonoscopy/endoscopy]	Week 8
Clinical Response - proportion of patients with: Colonoscopy/endoscopic improvement, defined as change from baseline in UCDAI endoscopy score	Week 8
Clinical Response - proportion of patients with: Clinical improvement, defined as partial UCDAI score decreasing ≥ 2 from baseline [not including the endoscopy/colonoscopy, but including the 3 other scores (stools, bleeding, Physicians rating of disease activity)] (parameter found predictive for patient-reported improvement of disease activity)	Week 2, 4 and 8
Disease-Specific QoLGlobal efficacy: feeling better than at baseline	Week 2, 4 and 8
Vital signs: weight, pulse, blood pressure, respiratory rate and oral temperature at every visit	Every visit
Disease-Specific QoLIBDQ (patient rating): change in the scores versus baseline	Week 4 and 8
Laboratory values (hematology, biochemistry)	At start, week 4 and week 8

Trial Locations

Locations (15)

Amrita Institute of Medical Sciences and Research Centre; 🇮🇳 Post,, India

Bangalore Clinisearch; 🇮🇳 Bangalore, KARNATAKA, India

Dayanand Medical College & Hospital; 🇮🇳 Ludhiana, PUNJAB, India

Dr. Bhatnagar's Clinic; 🇮🇳 Ahmadabad, GUJARAT, India

Gastro Care; 🇮🇳 Surat, GUJARAT, India

Gastro care Clinic; 🇮🇳 Rajkot, GUJARAT, India

GUT-N-HEPA CARE; 🇮🇳 Indore, MADHYA PRADESH, India

Lakeshore Hospital and Research Centre Limited; 🇮🇳 Bypass,, India

Medilink Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Medipoint Hospitals Pvt Limited; 🇮🇳 Pune, MAHARASHTRA, India

Scroll for more (5 remaining)

Amrita Institute of Medical Sciences and Research Centre

🇮🇳Post,, India

Dr. Shine Sadasivan

Principal investigator

04842801234

shines@aims.amrita.edu