Study of the Efficacy and Tolerance of Oral Treatment With a Total Freeze-dried Culture of Lcr Restituo® Sachets (Lactobacillus Rhamnosus Lcr35®) on Intolerance to Metformin (Diarrhoea) in Patients With Diabetes Type 2

NCT02730741 | Unknown Phase 2 DMC

• 2 other identifiers: PRO_2014-022014-003670-16
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The mechanisms of diarrhoea under metformin are poorly known. Recent data indicate that a change in gut flora might be responsible for this intestinal disorder. The effect of metformin on the gut flora has been extensively described. It has been shown that the therapeutic effect of metformin depends on the microbiota. In agreement with these data, a recent publication has shown that metformin's main site of action in humans was the intestine. In light of these results, it now seems plausible that metformin's effect on the gut flora is responsible not only for its therapeutic effect but also for its undesirable digestive effects. In this respect, Lactobacillus rhamnosus has shown anti-diarrhoeal effects (approximately 50% reduction in diarrhoeas) in the contexts of infection-caused dysbiosis and post-antibiotic dysbiosis. Hypothesis: Taking into account the favourable effect on intestinal dysbiosis-induced diarrhoeas observed with Lactobacillus rhamnosus, we put forward the hypothesis that Lactobacillus rhamnosus Lcr35® will have a favourable effect on metformin-induced diarrhoea.

Conditions

Antidiarrhoea

Keywords

diarrhoea; metfomin; type 2 diabetes; microbiota

Outcome Measures

Primary Outcomes (1)

• Compare number of treated patients who have had diarrhoea in the verum group and in the placebo group between Visit 2 and Visit 5. Diarrhoea evaluated using the Bristol stool scale (types 5 to 7)

  3 months

Study Arms (3)

Lcr restituo® sachet and placebo

EXPERIMENTAL

The active treatment (Total freeze-dried culture of Lcr restituo® sachet) at a rate of 2 sachets of 1.5 grams per day (one sachet in the morning and one in the evening) and the placebo at a rate of 2 sachets of 1.5 grams per day (one sachet in the morning and one in the evening).

Drug: Lcr restituo® sachet; Drug: Placebo

Lcr restituo® sachet

EXPERIMENTAL

The active treatment (Total freeze-dried culture of Lcr restituo® sachet) at a rate of 4 sachets of 1.5 grams per day (two sachets in the morning and two in the evening).

Drug: Lcr restituo® sachet

Placebo

PLACEBO COMPARATOR

The placebo at a rate of 4 sachets of 1.5 grams per day (two sachets in the morning and two in the evening).

Drug: Placebo

Interventions

Lcr restituo® sachet DRUG

symptomatic treatment of diarrhoea

Also known as: Bacilor

Lcr restituo® sachet; Lcr restituo® sachet and placebo

Placebo DRUG

Lcr restituo® sachet and placebo; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease-related
• Patients who, from a metabolic perspective, could benefit from metformin treatment, namely patients for whom the latest available hemoglobin glycated (HbA1c) is no older than 3 months, and higher that suggested in recommendations, and lower than 9%.
• Patients with type 2 diabetes who have not received metformin treatment for at least 2 months, or treated with a non-optimal dose of metformin, i.e. 1500 mg/day or less, due to a history of diarrhoea-type digestive intolerance reported with this drug.
• Patients who at the time of entering the study have a blood sugar self-monitoring device.
• Patients whose kidney function, evaluated in reference to creatinine clearance calculated using the Cockcroft formula, is 45ml/min or higher.
• Cohort-related:
• Patients aged between 18 and 75 years
• For women of childbearing age:
• to have a negative urine pregnancy test,
• and use a contraceptive method deemed effective by the investigator throughout the trial
• Patient able to speak and read French, having been informed of the study, and having voluntarily signed an Informed Consent Form
• Patient covered by a social security scheme

You may not qualify if:

• Disease-related:
• Patient presenting with cardinal signs of diabetes
• Treatment-related:
• Patients presenting with a contraindication to metformin treatment other than diarrhoea-type digestive intolerance manifestations.
• Patients treated with a Inhibitors of dipeptidyl peptidase 4 (DPP-IV inhibitor).
• Patients who presented with a serious adverse event associated with metformin prescription.
• Patients who have taken orlistat in the preceding month or who have taken antibiotics in the preceding month.
• Patients who have an allergy to one of the active ingredients or one of the excipients in the study product.
• Cohort-related:
• Patient with no referring physician.
• Patient deemed by the investigator as unable to participate in the study
• Patient unable to comply with the constraints of the protocol.
• Patient whose metabolic condition does not justify the initiation or dose increase of metformin treatment.
• History of bariatric surgery.
• Patient is immunodeficient, or has a chronic viral infection with the hepatitis B or C, or the human immunodeficiency virus (HIV virus)

Sponsors & Collaborators

• Biose: lead

Study Sites (1)

BIOSE

Aurillac, France

RECRUITING

MeSH Terms

Conditions

Diarrhea; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Pr. Jacques MOREAU

  Digestive unit - Hôpital RANGUEIL - Toulouse teaching hospital (CHU) France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard BOISSIERE

CONTACT

+330471468764; r.boissiere@biose.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 6, 2016
• Study Start: June 1, 2016
• Primary Completion: June 1, 2016
• Last Updated: January 19, 2018

Record last verified: 2018-01

Locations

FR (1)