AntidiarrhoeaPhase 2PROVAMENCT02730741
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
A Phase 2 study testing Lcr restituo® sachet in people with Antidiarrhoea, run by Biose at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Antidiarrhoea
- What is being tested?
- Lcr restituo® sachet
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2016to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- Disease-related:
- Patient presenting with cardinal signs of diabetes
- Patients presenting with chronic diarrhoea or with a history of chronic intestinal inflammatory disease or having presented with an episode of acute diarrhoea in the 10 days preceding the inclusion.
- 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).
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- 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 taken probiotics in the month preceding the inclusion visit.
- Patients who have taken prebiotics in the 15 days preceding the inclusion visit.
- 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)
- Patient is pregnant, planning a pregnancy, or without contraception.
- Breastfeeding patient.
- Patient with a previous illness which, according to the investigator, is likely to interfere with the study results or expose the patient to an additional risk.
- Patient linguistically unable (unable to speak or write French) or mentally unable to understand and sign the Informed Consent Form.
- Patient deprived of their liberty by order of the Courts or civil authorities or subject to a guardianship order.
- Patient who is likely to not comply with treatment.
- Patient unable to be contacted in the case of an emergency.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
BIOSE
Aurillac
NIVOLIEZ Mr Adrien, +330471465101, a.nivoliez@biose.com
Pr. Jacques MOREAU
About this study
Official title: Study of the Efficacy and Tolerance of Oral Treatment of Lcr Restituo® Sachets (Lactobacillus Rhamnosus Lcr35®) on Intolerance to Metformin (Diarrhoea) in Patients With Diabetes Type 2
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.
Read the detailed description
There is a diabetes pandemic: The number of diabetes patients is expected to reach 500 million worldwide by 2030, of which 90% suffering from type 2 diabetes.
Therapeutically, metformin remains the only recommended first-line treatment. However, the common digestive effects of this molecule, concerning 30 to 50% of patients, are a major obstacle to its prescription. The availability of a treatment preventing these unwanted effects would optimise the treatment of millions of diabetes patients. This would represent a considerable advantage in terms of public health due to the expected reduction in cardiovascular morbidity.
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. 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
- Being tested
- Lcr restituo® sachet, Placebo
- Keywords
- diarrhoea, metfomin, type 2 diabetes, microbiota
- Medical subject headings
- Diarrhea, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lcr restituo® sachetDrug
Also called Bacilor
symptomatic treatment of diarrhoea
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study startJun 2016
- Primary completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AntidiarrhoeaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Biose
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pr. Jacques MOREAU, Principal investigator, Digestive unit - Hôpital RANGUEIL - Toulouse teaching hospital (CHU) France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02730741
- Sponsor's protocol ID
- PRO_2014-02
- Other IDs
- 2014-003670-16, 2014
- Acronym
- PROVAME
- Status last verified
- Jan 2018
- First submitted
- 30 Mar 2016
- Last updated
- 19 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Efficacy and Tolerance of Oral Treatment of Lcr Restituo® Sachets (Lactobacillus Rhamnosus Lcr35®) on Intolerance to Metformin (Diarrhoea) in Patients With Diabetes Type 2
- ClinicalTrials.gov ID
- NCT02730741
- Acronym / sponsor ID
- PROVAME / PRO_2014-02
- Conditions
- Antidiarrhoea
- Keywords
- diarrhoea, metfomin, type 2 diabetes, microbiota
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- BioseIndustry (pharma, biotech, devices)
- Study start
- Jun 2016
- Primary completion
- Jun 2016 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
There is a diabetes pandemic: The number of diabetes patients is expected to reach 500 million worldwide by 2030, of which 90% suffering from type 2 diabetes.
Therapeutically, metformin remains the only recommended first-line treatment. However, the common digestive effects of this molecule, concerning 30 to 50% of patients, are a major obstacle to its prescription. The availability of a treatment preventing these unwanted effects would optimise the treatment of millions of diabetes patients. This would represent a considerable advantage in terms of public health due to the expected reduction in cardiovascular morbidity.
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. 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lcr restituo® sachet and placebo | Experimental | Drug: Lcr restituo® sachet, Drug: PlaceboThe 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). |
| Lcr restituo® sachet | Experimental | Drug: Lcr restituo® sachetThe 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). |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo at a rate of 4 sachets of 1.5 grams per day (two sachets in the morning and two in the evening). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (25 listed)
- Patient presenting with cardinal signs of diabetes
- Patients presenting with chronic diarrhoea or with a history of chronic intestinal inflammatory disease or having presented with an episode of acute diarrhoea in the 10 days preceding the inclusion.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lcr restituo® sachetAlso: Bacilorsymptomatic treatment of diarrhoea | Drug | Lcr restituo® sachet, Lcr restituo® sachet and placebo |
| Placebo | Drug | Lcr restituo® sachet and placebo, Placebo |
Primary outcome
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)
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2018.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pr. Jacques MOREAU principal investigator
Digestive unit - Hôpital RANGUEIL - Toulouse teaching hospital (CHU) France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lcr restituo® sachet in people with Antidiarrhoea, run by Biose at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Richard BOISSIERE (+330471468764, r.boissiere@biose.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2018.