Efficacy and Safety of Escherichia coli DSM 17252 in Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-512104-19-00
- Protocol
- SymSF2
- Sponsor
- SymbioPharm GmbH
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this randomized, double-blind, placebo-controlled, multi-centre trial is to investigate the **effectiveness** of oral treatment with Symbioflor®2, containing living bacteria of **Escherichia coli DSM 17252**, in patients with diarrhoea-predominant **Irritable Bowel Syndrome (IBS-D)**. The study aims to evaluate the improvement in the frequency and severity of IBS-D symptoms compared to placebo. This is clinically relevant as IBS-D significantly impacts patients' quality of life, and effective treatments are needed to manage its symptoms.
Secondary objectives include determining the **safety** and **tolerability** of Symbioflor®2 in the same patient population. Understanding the safety profile is crucial for assessing the overall benefit-risk ratio of the treatment.
Participants
The clinical trial focuses on evaluating the effectiveness of **Symbioflor®2** in patients diagnosed with **Irritable Bowel Syndrome** with diarrhea predominance (IBS-D). The study population comprises both male and female outpatients aged 18 years and older. Participants are required to have a confirmed diagnosis of IBS according to the Rome IV criteria, which includes recurrent abdominal pain associated with defecation, changes in stool frequency, and form. The trial does not involve a vulnerable population. Participants must have undergone a colonoscopy with no clinically relevant findings if they are younger than 50 years or within the last five years if they are 50 years or older. Female participants of childbearing potential must adhere to strict contraceptive measures and have a negative pregnancy test at screening and baseline. The trial requires participants to maintain consistent dietary habits, fiber and fluid intake, and physical activity levels throughout the study. Additionally, participants must refrain from using other IBS treatments, including probiotics, and possess sufficient German language skills to comprehend trial instructions and rating scales. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy, safety, and tolerability of oral treatment with living bacteria of **Escherichia coli DSM 17252** (Symbioflor®2) in patients with **diarrhea-predominant irritable bowel syndrome (IBS-D)**. The trial will span an estimated duration from October 2019 to June 2027, with a maximum treatment period of 26 weeks for each participant. The study involves multiple visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis according to Rome IV, and willingness to comply with study requirements. Participants will be required to refrain from significant changes in diet, fiber intake, fluid intake, or physical activity during the study.
Following the screening, eligible participants will be randomized to receive either the active treatment or a placebo, which is identical in appearance and composition to the active formulation but lacks the active ingredient. The primary endpoints include response rates measured by the Bristol Stool Scale and the 11-point numeric rating scale for abdominal pain intensity. Secondary endpoints involve the IBS Global Assessment of Improvement Scale and further assessments of abdominal pain intensity. Study visits will occur at regular intervals to monitor the participants' progress, adherence to the protocol, and any adverse events. The end-of-study visit will conclude the trial for each participant, with a comprehensive evaluation of the treatment's impact on IBS-D symptoms.
Participants are expected to be involved in the study for the full 26-week treatment period unless conditions arise that necessitate early termination, such as significant protocol deviations, adverse events, or withdrawal of consent. The trial aims to provide robust data on the effectiveness and safety of Symbioflor®2 in managing IBS-D, contributing valuable insights into potential therapeutic options for this condition.
Treatment
The clinical trial involves the administration of **Symbioflor®2**, an experimental medication containing **Escherichia coli DSM 17252** as the active substance. This medication is formulated as oral drops, specifically a suspension, and is manufactured by Symbiopharm GmbH. The maximum daily dosage is 60 drops, with a total maximum dose of 10,710 drops over a treatment period of 26 weeks. The medication is administered orally, and its primary role in the trial is to evaluate its efficacy, safety, and tolerability in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D).
The trial also includes a **placebo** suspension, which is identical in appearance, weight, and composition to the Symbioflor®2 liquid formulation, except for the omission of the active ingredient. The placebo consists of sodium chloride, magnesium sulphate 7H2O, potassium chloride, calcium chloride 2H2O, magnesium chloride 6H2O, and purified water. The placebo is administered in the same manner as the experimental medication, with a maximum daily dosage of 60 drops and a total maximum dose of 10,710 drops over 26 weeks. The placebo serves as a comparator to assess the true efficacy of the experimental treatment.
Efficacy
The efficacy of the clinical trial will be assessed through both primary and secondary endpoints. The primary endpoints include the response rate measured by the Bristol Stool Scale (BSS) and the 11-point numeric rating scale (NRS) for **Abdominal Pain Intensity**. The BSS response is defined as at least a 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 out of 26 measurements. The NRS response is defined as a decrease in the weekly average of the worst abdominal pain.
Secondary endpoints involve the response rate measured by the 7-point IBS Global Assessment of Improvement Scale (IBS-GAI) and the 11-point NRS during the 26 weeks of treatment. The IBS-GAI response is defined as at least 50% moderate or substantial improvement during the treatment period. The NRS response for secondary endpoints is defined as at least a 30% improvement in Abdominal Pain Intensity weekly response compared to baseline for a minimum of 20 out of 26 measurements.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female outpatients aged ≥18 years • Diagnosis of irritable bowel syndrome 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 (performed for all patients younger than 50 years and for patients ≥50 years of age within the last 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 the study • 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
Exclusion Criteria
- 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 9.3) • Serum potassium, magnesium, or calcium values outside the normal range at screening and clinically significant • Serum aspartate transaminase (AST), alanine transaminase (ALT), or gamma glutamyl-transferase (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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 01 Oct 2019 | 422 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo suspension is identical to Symbioflor®2 liquid formulation in appearance, weight and composition, with the exception that the active ingredient will be omitted. Placebo constitutes are sodium chloride, magnesium sulphate 7H2O, potassium chloride, calcium chloride 2H2O, magnesium chloride 6H2O, and purified water | Placebo | N/A | ORAL USE | 60 | 26 | N/A |
Symbioflor 2 Tropfen zum Einnehmen, Suspension | Test | TROPFEN ZUM EINNEHMEN, SUSPENSION | ORAL USE | 60 | 26 | PRD3544668 |