Clinical trial NCT03718715: The Interaction Between Metformin and Microbiota - the MEMO Study.
Official title: The Interaction Between Metformin and Microbiota - the Reason for Gastrointestinal Side Effects?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Type 2 Diabetes Mellitus
Keywords: Metformin
Gastrointestinal side effects
Microbiota
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: Göteborg University
name: Örebro University, Sweden
name: Linkoeping University
name: Karolinska Institutet
First posted: 2018-10-24
Enrollment: 600
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: newly diagnosed patients with type 2 diabetes without previous treatment with metformin.

Brief summary: Metformin has been used in Sweden since 1957, and it is recommended as first line therapy for type 2-diabetes (T2D) in national and international guidelines. However, adverse effects involving diarrhea, constipation, bloating, and abdominal pain are common which leads to discontinuation of medication or not being able to reach therapeutic doses. Here the investigators will perform a prospective study to investigate whether i) participants with T2D who experience adverse events following metformin treatment have an altered microbiota at baseline compared to participants without adverse events and ii) if the microbiota is altered in participants during onset of adverse events. The investigators hypothesis is that adverse effects associated with metformin are caused by an altered gut microbiota, either at base line or following metformin treatment. The study design is a nested case-cohort study. The investigators will recruit 600 patients and expect 200 individuals to have side effects and 400 without during a 24-month study period. Fecal samples will be collected at baseline, 2 months, and 4 months or when gastrointestinal symptoms occur. All fecal samples will be sequenced by 16s rRNA (ribosomal ribonucleic acid) sequencing to obtain a baseline microbiota profile; a subpopulation consisting of homogenous groups of participants will be in depth-analyzed using shotgun sequencing. If the hypothesis is confirmed this project may lead to bacterial therapies that will allow more patients tolerate metformin.


Eligibility criteria: Inclusion criteria:

* Type 2 diabetes (diagnosis set within the last 12 months)
* planned metformin treatment
* Age: 40 - 80 years
* Have provided written informed consent.

Exclusion criteria:

* already started treatment with Metformin
* intestinal disease incl. irritable bowel syndrome
* treatment with antibiotics in the last 3 months
* Inflammatory disorder t.ex. rheumatoid arthritis
* anemia, haemoglobinopathy
* alcohol or drug abuse
* cancer disease under treatment

Primary outcomes:
measure: change from baseline in the fecal microbiota composition by detecting bacteria families with help of relative abundance (%) and diversity metrics
timeFrame: 4 months
Secondary outcomes:
measure: genetic correlation between Microbiota and gastrointestinal side effects
timeFrame: 4 months
measure: number of patients with gastrointestinal side effects
timeFrame: 4 months
measure: rate of gastrointestinal side effects
timeFrame: 4 months
measure: time to first appearance of gastrointestinal side effects
timeFrame: 4 months
measure: time to first appearance of side effects which requires dose changes in the Metformin treatment
timeFrame: 4 months
measure: time to first appearance of side effects which requires termination of the Metformin treatment
timeFrame: 4 months
measure: correlation between microbiota and beneficial glucose lowering response
timeFrame: 4 months
Other outcomes:
Locations:
city: Umeå
country: Sweden
facility: Region Västerbotten
Study officials:
affiliation: Umeå University
name: Olov Rolandsson, Professor
role: PRINCIPAL_INVESTIGATOR
References: