Probiotic Intervention for Digestive Health in Obese Patients Initiating GLP-RA Treatment

NCT07213323 | Not Yet Recruiting

• 2 other identifiers: 69HCL25_03212025-A01248-41
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity is a prevalent chronic disease affecting 17% of the French population. Treatment involves multiple factors, with pharmacotherapy playing an increasingly important role. GLP-1 receptor agonists (GLP1 RAs) are considered revolutionary in obesity treatment, with three approved molecules available in France: liraglutide, semaglutide, and tirzepatide. These treatments, combined with a healthy lifestyle, induce significant weight loss: 9% with liraglutide, 15% with semaglutide, and 20% with tirzepatide. The most common adverse events (AEs) associated with GLP-1 RAs are gastrointestinal (GI) disorders, including nausea, vomiting, diarrhea, and abdominal pain. These AEs are dose-dependent and often decline over time. In phase 3 trials, semaglutide 2.4 mg showed higher rates of GI AEs compared to placebo, but most were mild to moderate and transient. GI AEs led to dose reduction or temporary treatment interruption in 12.5% of participants, with few permanent discontinuations. Probiotics, are live microorganisms that benefit the host by improving gut microflora. Probiotics has been clinically proven to benefit gastrointestinal health. Probiotics may reduces symptoms of irritable bowel syndrome (IBS), improves gut barrier function, reduces inflammation, and decreases the incidence of C. difficile infection (CDI) in patients taking antibiotics. Probiotics is therefore theorized to potentially reduce GI side effects associated with GLP-1 RA treatment for obesity. Hypothesis Probiotics will prevent and limit the digestive disorders induced by GLP-1 R agonists, particularly during the dose escalation period. This would allow better digestive tolerance of the treatments, limiting the number of definitive treatment interruptions, facilitating compliance and dose escalation with a larger number of subjects at full dose and therefore with better systemic exposure to the compounds, a key factor in their effects on weight loss.

Conditions

Obesity &Amp; Overweight; Digestive Disorders

Keywords

GLP1 R-agonist; Probiotics; Quality of life

Outcome Measures

Primary Outcomes (1)

• Assessment of the Limitation of the impairment in digestive quality of life during the dose escalation of GLP1-RA (semaglutide or tirzepatide)

  Assessment using partial GIQLI Score (5 items: 1,27,31,32,33 of the total GIQLI) in each GLP-1 RA group measured 4 weeks following the previous dose escalation, with the GLP1-RA dose standardized on a 0-1 scale. Item 1 for abdominal pain, Item 27 for dyspepsia, Item 31 for diarrhea, item 32 for constipation and Item 33 for nausea. For each item, 5 responses will be proposed to the patients and for each answer, a score ranging from 0 to 4 will be assigned The highest score is 20 and defines a more favorable health state

  Every 5 weeks

Secondary Outcomes (20)

• Digestive quality of life

  From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment

• Nausea

  From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment

• Dyspepsia

  From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment

• Diarrhea

  From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment

• Constipation

  From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment

Study Arms (2)

Probiotics

EXPERIMENTAL

Obese subjects who are going to start a GLP-1 R-agonist (semaglutide or tirzepatide) as part of their weight management in routine clinical practice will received during 26 weeks 1 capsule a day every morning of probiotics that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment.

Dietary Supplement: Probiotics (Natural product)

Placebo

PLACEBO COMPARATOR

Obese subjects who are going to start a GLP-1 R-agonist (semaglutide or tirzepatide) as part of their weight management in routine clinical practice will received during 26 weeks 1 capsule a day every morning of PLACEBO that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment.

Other: Placebo

Interventions

Probiotics (Natural product) DIETARY_SUPPLEMENT

Participants will be instructed to daily take, during 26 weeks (that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment) one capsule of a probiotic with water at room temperature with the first meal. Dosage levels: 1 capsule Digestive Quality of life during the study will be assessed.

Probiotics

Placebo OTHER

Participants will be instructed to daily take, during 26 weeks (that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment) one capsule of PLACEBO with water at room temperature with the first meal. Digestive Quality of life during the study will be assessed.

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:

• Patient who is going to start a GLP-1 RA (semaglutide or tirzepatide) for weight management
• Men or Women
• BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 associated with one or more co-morbidities (arterial hypertension, sleep apnea, dyslipidemia, arthritis)
• Between 18 and 75 years old
• In the opinion of the investigator, the patient must have adequate support to comply with the entire study requirements as described in the protocol (e.g. transportation to and from trial site, ability to understand and fill the self-rating scales, drug compliance, availability to attend to the scheduled visits, etc…).
• Patient who agrees to be included in the study and who signs the informed consent form
• Female participants of childbearing potential must agree to use effective contraception
• Patient affiliated to a healthcare insurance plan

You may not qualify if:

• Criteria relating to the study population:
• Patients under 18 years old
• Patient with contraindication to semaglutide or tirzepatide according to the Summary of Product Characteristics (SPC).
• Patients scheduled for bariatric surgery during the study period
• Patients who have had bariatric surgery in the last 12 months
• Patient with a current diagnosis of diabetes.
• Patients with a current diagnosis of liver cirrhosis, short bowel syndrome or inflammatory bowel disease (IBD).
• Patients with severely weakened immune system.
• Clinically unstable medical disease, including cardiovascular, hepatic, renal, gastrointestinal, pulmonary, metabolic, endocrine, or other systemic disease.
• Product criteria:
• Patient with known allergy to the product of the study
• Prohibited treatments :
• Current associated treatments or used in the last 30 days: GLP-1 RA, Anti-obesity drugs (AOD), Corticosteroids, Atypical neuroleptics, Antibiotics, Probiotics, Prebiotics
• Regulatory criteria :
• Persons deprived of their liberty by a judicial or administrative decision

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Lyon Sud

Pierre-Bénite, 69495, France

Location

MeSH Terms

Conditions

Obesity; Overweight; Digestive System Diseases

Interventions

Probiotics; Biological Products

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Complex Mixtures

Study Officials

• Emmanuel DISSE, PUPH

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emmanuel DISSE, PUPH

CONTACT

+33478861484; Emmanuel.disse@chu-lyon.fr

Dominique DELAUNAY, PhD

CONTACT

+33472110064; Dominique.delaunay@chu-lyon.Fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind study : patients and investigators will not be informed of the approach (probiotics or placebo ) which will be used.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, double blind, randomized, monocentric, 2 parallel groups (1:1) study evaluating superiority probiotics over placebo in limiting the impairment in digestive quality of life over 24-week in patients with obesity initiating GLP-1 RA (semaglutide or tirzepatide) for weight control.

Study Record Dates

• First Submitted: September 18, 2025
• First Posted: October 8, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): December 15, 2027
• Last Updated: October 8, 2025

Record last verified: 2025-10

Locations

FR (1)