Randomized, double-blind, placebo-controlled, multi-centre trial to evaluate the efficacy, safety and tolerability of oral treatment with living bacteria of E. coli DSM 17252 (Symbioflor®2) in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D)
- Conditions
- K58.1 IBS-D
- Registration Number
- DRKS00018965
- Lead Sponsor
- SymbioPharm GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 422
• Male and female outpatients aged =18 years
• Diagnosis of IBS-D according to Rome IV: 1. Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months associated with two or more of the following criteria - related to defecation - associated with a change in frequency of stool - associated with a change in form (appearance) of stool
2. Criteria fulfilled for the last 3 months and
3. IBS symptom onset = 6 months
4. IBS-D subtype with abnormal stools being usually diarrhoea
• Colonoscopy with no clinically relevant findings (= 5 years)
• Female patients of childbearing potential must be either surgically sterilized or use a highly effective method of contraception with a negative pregnancy test at screening and baseline/day 0
• Willingness to refrain from significant changes in diet, fibre intake, fluid intake, or physical activity during trial participation
• Willingness to refrain from the use of other medications for IBS treatment, including probiotic medication
• Ability to comply with treatment
• Sufficient knowledge of German language to understand trial instructions and rating scales
• Written informed consent prior to enrolment
• Email account and internet access available
• History of abdominal surgery within the 6 months prior to screening
• Presence or suspected presence of unstable coronary artery disease, untreated organic gastrointestinal disease and uncontrolled metabolic diseases causing IBS-related symptoms, or collagen vascular disease within the 6 months prior to screening
• Lactose or fructose intolerance explaining the symptoms (in doubtful cases, a diagnostic test has to be performed)
• Coeliac disease (in doubtful cases, a diagnostic test has to be performed)
• Confirmed bile acid malabsorption by SeHCAT-Test or successful treatment by bile acid sequestrant
• Change of diet e.g. FODMAP, gluten-free within last 3 months
• Abnormal endoscopy/ abdominal ultrasound requiring further investigation
• Any alarm symptoms including uninvestigated anaemia, rectal bleeding, weight loss, or unresolved fever within the 6 months prior to Screening
• Participation in another clinical trial or use of any investigational drug within 30 days or 5 half-lives (whichever is longer) before dosing
• Evidence of current or recent alcohol or drug abuse within 6 months prior to screening
• History or evidence of current laxative abuse
• Pregnancy or breast feeding
• Any illness or condition that might impact the safety of study drug administration or evaluability of drug effect based on Investigator’s discretion.
• No consent to recording and processing of pseudonymised data according to legal requirements
• Patients who are committed to a clinic or similar institution by official or judicial order
• Hypersensitivity to active ingredient or any excipients of the medicinal product
Patients will be excluded from randomization to a treatment group if they have/are:
• Current intake of prohibited medications except for rescue purposes (refer to 10.3)
• Serum potassium, magnesium, or calcium values outside the normal range at screening and clinically significant
• Serum aspartate transaminase (AST), alanine transaminase (ALT), or gamma glutamyltransferase (GGT) =3 times the upper limit of the normal range at screening or baseline, or a bilirubin value =2 times the upper limit of the normal range at screening
• Abnormal thyroid stimulating hormone (TSH) value at screening, unless the free T4 value is normal; (Note: Levothyroxine will be allowed, if on stable dose for at least 30 days prior to screening and no changes expected during study)
• Any further laboratory value(s) outside the laboratory reference range at screening considered clinically significant by the Investigator
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Response will be assessed by a combined primary endpoint consisting of two co-primary components (see 14.6.3.1)<br>A responder is defined as a patient who fulfils the following criteria:<br>1. Response rate measured by Bristol Stool Scale. BSS response is defined as at least 50% reduction in the number of days with at least one stool that has a consistency of 6 or 7 per week compared to baseline for a minimum of 13 of the 26 measurements (i.e. at least 50% improvement of stool consistency during treatment).<br>and<br>2. Response rate measured by the 11-point numeric rating scale (NRS). Abdominal Pain Intensity response is defined as a decrease in the weekly average of worst abdominal pain of at least 30% compared to baseline for a minimum of 13 of the 26 measurements (i.e. at least 50% improvement of Abdominal Pain Intensity during treatment)
- Secondary Outcome Measures
Name Time Method