The Interaction Between Metformin and Microbiota - the MEMO Study.

Type 2 Diabetes Mellitus Clinical Trial

— MEMO  

Official title:

The Interaction Between Metformin and Microbiota - the Reason for Gastrointestinal Side Effects?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03718715
• Other study ID #: MEMO
• Status: Recruiting
• Start date: February 20, 2019
• Est. completion date: March 2022

Study information

• Verified date: November 2020
• Source: Umeå University
• Contact: Olov Rolandsson, Professor
• Phone: +46 90 786 50 00
• Email: olov.rolandsson[@]umu.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: March 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Metformin
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.

Locations

Country	Name	City	State
Sweden	Region Västerbotten	Umeå

Sponsors (5)

Lead Sponsor	Collaborator
Umeå University	Göteborg University, Karolinska Institutet, Linkoeping University, Örebro University, Sweden

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	genetic correlation between Microbiota and gastrointestinal side effects	The microbiota genome and the relation to the appearance of gastrointestinal side effects will be analysed.	4 months
Secondary	number of patients with gastrointestinal side effects	A questionnaire will be answered at baseline, after 2 and 4 months and refers to a period of 2 weeks before study visit. Six different side effects will be monitored: loss of appetite, nausea, vomiting, diarrhea, meteorism, stomach ache.	4 months
Secondary	rate of gastrointestinal side effects	Changes in the rate of side effects using questionnaire at baseline, after 2 and 4 months.The answer possibilities are: never, one or a few times, daily, multiple times a day.	4 months
Secondary	time to first appearance of gastrointestinal side effects	How many months till the onset of side effects during metformin treatment: depending on the time of assessment, 2 or 4 months	4 months
Secondary	time to first appearance of side effects which requires dose changes in the Metformin treatment	Analysing changes in metformin treatment and relation to appearance of side effects	4 months
Secondary	time to first appearance of side effects which requires termination of the Metformin treatment	Analysing length of metformin treatment and relation to appearance of side effects	4 months
Secondary	correlation between microbiota and beneficial glucose lowering response	Plasma glucose will be analysed at baseline, after 2 and 4 months of Metformin treatment and correlated to the changes in the composition of microbiota.	4 months