The Interaction Between Metformin and Microbiota - the MEMO Study.

NCT03718715 | Unknown

• 1 other identifier: MEMO
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Metformin; Gastrointestinal side effects; Microbiota

Outcome Measures

Primary Outcomes (1)

• change from baseline in the fecal microbiota composition by detecting bacteria families with help of relative abundance (%) and diversity metrics

  Faeces samples will be collected at baseline, after 2 months and after 4 months of Metformin treatment and analysed using 16S rRNA sequencing, whole genome shotgun sequencing and metagenomic analyses

  4 months

Secondary Outcomes (7)

• genetic correlation between Microbiota and gastrointestinal side effects

  4 months

• number of patients with gastrointestinal side effects

  4 months

• rate of gastrointestinal side effects

  4 months

• time to first appearance of gastrointestinal side effects

  4 months

• time to first appearance of side effects which requires dose changes in the Metformin treatment

  4 months

Study Arms (1)

prospective cohort

All participants receive Metformin in accordance to the ordinary therapy practice. They will be part of one subject group/cohort. After onset of metformin treatment the subjects who develop gastrointestinal side effects will be compared with cases without gastrointestinal side effects.

Drug: Metformin

Interventions

Metformin DRUG

Receiving Metformin is no study intervention. The investigators have no influence on the Metformin treatment. All participants receive Metformin provided by the health care system. The individual case determine dose and frequency of the treatment as part of the usual therapy guidelines.

prospective cohort

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

newly diagnosed patients with type 2 diabetes without previous treatment with metformin.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Umeå University: lead
• Göteborg University: collaborator
• Örebro University, Sweden: collaborator
• Linkoeping University: collaborator
• Karolinska Institutet: collaborator

Study Sites (1)

Region Västerbotten

Umeå, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma samples, Feces samples

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Olov Rolandsson, Professor

  Umeå University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olov Rolandsson, Professor

CONTACT

+46 90 786 50 00; olov.rolandsson@umu.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: October 24, 2018
• Study Start: February 20, 2019
• Primary Completion: December 1, 2021
• Study Completion: March 1, 2022
• Last Updated: November 4, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)