Type 2 Diabetes MellitusMEMONCT03718715
The Interaction Between Metformin and Microbiota - the MEMO Study.
An observational study of Type 2 Diabetes Mellitus, run by Umeå University at 1 site in Sweden.
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… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Metformin
- How many people
- 600 participants
- Where
- 1 siteSweden
- Study dates
- 20 Feb 2019to Mar 2022
- Phase
- Observational
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: newly diagnosed patients with type 2 diabetes without previous treatment with metformin.
Who may be able to join
- Type 2 diabetes (diagnosis set within the last 12 months)
- planned metformin treatment
- Age: 40 - 80 years
- Have provided written informed consent.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Region Västerbotten
Umeå
Kenny Kalin, MD, 070-7991186, kenny.kalin@umu.se
About this study
Official title: The Interaction Between Metformin and Microbiota - the Reason for Gastrointestinal Side Effects?
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
- Being tested
- Metformin
- Keywords
- Metformin, Gastrointestinal side effects, Microbiota
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 months
Secondary outcomes (7)
genetic correlation between Microbiota and gastrointestinal side effects
The microbiota genome and the relation to the appearance of gastrointestinal side effects will be analysed.
Measured: 4 months
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.
Measured: 4 months
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.
Measured: 4 months
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
Measured: 4 months
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
Measured: 4 months
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
Measured: 4 months
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.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start20 Feb 2019
- Primary completionDec 2021 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Umeå UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Umeå University
- Sponsor type
- University, hospital or other
- Collaborators
- Göteborg University, Örebro University, Sweden, Linkoeping University, Karolinska Institutet
- Responsible party
- Principal investigator, Olov Rolandsson, Umeå University
- Investigators
- Olov Rolandsson, Professor, Principal investigator, Umeå University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03718715
- Sponsor's protocol ID
- MEMO
- Acronym
- MEMO
- Status last verified
- Nov 2020
- First submitted
- 4 May 2018
- Last updated
- 4 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Interaction Between Metformin and Microbiota - the Reason for Gastrointestinal Side Effects?
- ClinicalTrials.gov ID
- NCT03718715
- Acronym / sponsor ID
- MEMO / MEMO
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Metformin, Gastrointestinal side effects, Microbiota
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Umeå UniversityUniversity, hospital or other
- Collaborators
- Göteborg University, Örebro University, Sweden, Linkoeping University, Karolinska Institutet
- Study start
- 20 Feb 2019 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 24 Oct 2018 (actual)
- 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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| prospective cohort | – | Drug: MetforminAll 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. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- newly diagnosed patients with type 2 diabetes without previous treatment with metformin.
Key inclusion criteria (4 listed)
- Type 2 diabetes (diagnosis set within the last 12 months)
- planned metformin treatment
- Age: 40 - 80 years
- Have provided written informed consent.
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| MetforminReceiving 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. | Drug | prospective cohort |
Primary outcome
change from baseline in the fecal microbiota composition by detecting bacteria families with help of relative abundance (%) and diversity metrics
Time frame: 4 months
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
7 secondary outcomes
genetic correlation between Microbiota and gastrointestinal side effects
Time frame: 4 months
number of patients with gastrointestinal side effects
Time frame: 4 months
rate of gastrointestinal side effects
Time frame: 4 months
time to first appearance of gastrointestinal side effects
Time frame: 4 months
time to first appearance of side effects which requires dose changes in the Metformin treatment
Time frame: 4 months
time to first appearance of side effects which requires termination of the Metformin treatment
Time frame: 4 months
correlation between microbiota and beneficial glucose lowering response
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Individual participant dataSharing planned: No
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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.
Olov Rolandsson, Professor principal investigator
Umeå University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes Mellitus, run by Umeå University at 1 site in Sweden.
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 4 inclusion and 7 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 4 Nov 2020. 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 Sweden. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Olov Rolandsson, Professor (+46 90 786 50 00, olov.rolandsson@umu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change from baseline in the fecal microbiota composition by detecting bacteria families with help of relative abundance (%) and diversity metrics (time frame: 4 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 4 Nov 2020.