Probiotic Intervention for Digestive Health in Obese Patients Initiating GLP-RA Treatment
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorHospices Civils de Lyon
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Probiotics (Natural product)
Dietary supplementParticipants 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.
Placebo
Other interventionParticipants 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.
Treatment groups
50 Participants
are divided into 2 treatment groupsGroup A: ProbioticsExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
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
Time frame
Every 5 weeksSecondary outcomes
1
Digestive quality of life
Comparison between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of the partial GIQLI Scores (Questions 1,27,31,32,33). 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 and for each answer, a score ranging from 0 to 4. The highest score is 20 and defines a more favorable health state
Time frame
From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment2
Nausea
Comparison of nausea between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 33) of nausea score ranging from 0 to 4. 4 defines the more favourable score
Time frame
From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment3
Dyspepsia
Comparison of dyspepsia between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 27) of dyspepsia score ranging from 0 to 4. 4 defines the more favourable score
Time frame
From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment4
Diarrhea
Comparison of diarrhea between the probiotics group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 31) of diarrhea score ranging from 0 to 4. 4 defines the more favourable score
Time frame
From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov