HealthyPhase 1NCT02546050
The Effect of Metformin on Composition of Human Gut Bacteria
A Phase 1 study testing Metformin in people with Healthy, run by Oluf Borbye Pedersen at 1 site in Denmark.
Trial summary
OBJECTIVE: Investigate structural changes in the human gut microbiota and associated changes in metabolic markers in urine, saliva, blood and fecal samples following metformin treatment. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2015to Feb 2016
- Phase
- Phase 1
- 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 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male
- HbA1c < 5.7 % (39 mmol/mol)
- Caucasian (self-report of parental ethnicity)
- Weight stabile with 18.5 kg/m2 < BMI < 27.0 kg/m2
- Normal kidney function as evaluated by normal p-creatinine for age
Who cannot join
- Oral intake of any form of prescribed medication two months prior to recruitment
- Chronic or acute illness
- Previous gastro-intestinal operation excluding appendicitis
- Any other significant medical reason for exclusion as determined by the investigator
- Unable to give informed consent
- Need of medical treatment during the study period
Trial locations and contacts
1 site in 1 country.
Denmark1 site
The Novo Nordisk Foundation Center of Basic Metabolic Research, Section for Metabolic Genetics, University of Copenhagen
Copenhagen, Copenhagen Ø, 2100
About this study
Official title: Effects of Metformin on Human Gut Microbiota
OBJECTIVE: Investigate structural changes in the human gut microbiota and associated changes in metabolic markers in urine, saliva, blood and fecal samples following metformin treatment.
DESIGN: An, 18 week, one-armed cross over intervention trial consisting of a 6-week pre-intervention period, 6-week intervention period and a 6-week post-intervention period. 25 healthy young men will be included in the trial.
INTERVENTION: Six-week Metformin treatment to young healthy men.
Read the detailed description
An, 18 weeks, one-armed cross over intervention trial consisting of a 6-weeks pre-intervention period, 6-weeks intervention period and a 6-weeks post-intervention period. 25 healthy young men will be included in the trial. The pre-intervention period is the control period with no treatment. During the intervention period participants will receive 500 mg of metformin once daily the 1st week, then 500 mg twice daily the 2nd week, 1000 mg + 500 mg daily the 3rd week and 1000 mg + 1000 mg daily the remaining three weeks. Post-interventional investigators will examine gut microbiota of the participants 6 weeks after completion of the intervention period.
MESUREMENTS: Altered composition of gut microbiota as investigated by 16S rRNA sequencing is the primary outcome of this study. Secondary outcomes are to investigate changes in metabolic and inflammatory markers in blood and fecal samples. Blood, urine, saliva and fecal samples will be stored for future studies.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | 18 weeks study with intervention during week 6 to 12: the intervention consist of 500 mg of metformin once daily for week 7, then 500 mg twice daily week 8, 1000 mg + 500 mg daily week 9 and 1000 mg + 1000 mg daily for weeks 10-12. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Structural changes in the human gut microbiota.
Fecal samples are collected in order to characterize the gut microbiota composition.
Microbial DNA will be subjected to sequencing, microbial gene analyses, including taxonomic and functional annotation.
Measured: Baseline, 4 , 7, 8, 10, 11 , 13, 16, and 18 weeks
Secondary outcomes (14)
Changes in plasma glucose and HbA1c levels
Venous blood will be collected. The samples will be analyzed for plasma glucose and HbA1c, and correlated to changes in gut microbiota composition
Measured: Baseline and at week 7,10,13 and 18
Changes in insulin metabolism
Venous blood will be collected. The samples will be analyzed for serum insulin and C-peptide levels. Changes will be correlated to changes in gut microbiota composition.
Measured: Baseline and at week 7,10,13 and 18
Changes in inflammatory markers in blood samples.
Venous blood will be collected. The samples will be analyzed for markers of inflammation such as high sensitive C-reactive protein.
Measured: Baseline and at week 7,10,13 and 18
Changes in kidney function tests.
Venous blood will be collected. The samples will be analyzed for plasma creatinine and correlated to gut microbiota changes
Measured: Baseline and at week 7,10,13 and 18
Changes in liver function tests.
Venous blood will be collected. The samples will be analyzed for liver function test and correlated to gut microbiota changes
Measured: Baseline and at week 7,10,13 and 18
Serum Cobalamin
Venous blood will be collected. The samples will be analyzed for serum cobalamin and correlated to gut microbiota changes
Measured: Baseline and at week 7,10,13 and 18
Metformin plasma level
Plasma levels of metformin will be measured at visits 3 and 4 in order to test for compliance. Plasma metformin concentrations will be correlated to changes in gut microbiota composition and function
Measured: At week 10 and 13.
Blood pressure
Systolic and diastolic blood pressure are measured in the inclined position after a five minute rest using an automated sphygmomanometer. The measurement is repeated three times. Participants are instructed not to talk during the measurements.
Measured: Baseline and at week 7,13 and 18
Heart rate
Heart rate is measured in the inclined position after a five minute rest using an automated sphygmomanometer. The measurement is repeated three times. Participants are instructed not to talk during the measurements.
Measured: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Weight is measured using standardized procedures.
Measured: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Height is measured using standardized procedures.
Measured: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Waist- and hip circumference are measured using standardized procedures.
Measured: Baseline and at week 7,13 and 18
Bio-electrical impedance.
Body composition will be measured through bio-electrical impedance
Measured: Baseline and at week 7,13 and 18
GI symptoms
Changes in gastrointestinal symptoms of participants by validated VAS-questionnaire concerning following parameters: Overall abdominal symptoms, abdominal pain, bloating, flatulence, satisfaction with stool consistence, constipation, diarrhea, tiredness, nausea, metallic taste.
Measured: Baseline and at week 7, 10, 13 and 18.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2015 (estimated)
- Study startJun 2015
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oluf Borbye Pedersen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Oluf Borbye Pedersen, University of Copenhagen
- Investigators
- Oluf Pedersen, MD, Professor, Principal investigator, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02546050
- Sponsor's protocol ID
- NNF-CBMR 2015-000199-86
- Other IDs
- 2015-000199-86, 2015
- Status last verified
- Feb 2016
- First submitted
- 1 Jul 2015
- Last updated
- 17 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bryrup T, Thomsen CW, Kern T, Allin KH, Brandslund I, Jorgensen NR, Vestergaard H, Hansen T, Hansen TH, Pedersen O, Nielsen T. Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study. Diabetologia. 2019 Jun;62(6):1024-1035. doi: 10.1007/s00125-019-4848-7. Epub 2019 Mar 23.
PubMed 30904939
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Metformin on Human Gut Microbiota
- ClinicalTrials.gov ID
- NCT02546050
- Acronym / sponsor ID
- NNF-CBMR 2015-000199-86
- Conditions
- Healthy
- Keywords
- Gut microbiota, metformin, Metabolism, Metagenomics, Metabolomics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Oluf Borbye PedersenUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 10 Sep 2015 (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.
OBJECTIVE: Investigate structural changes in the human gut microbiota and associated changes in metabolic markers in urine, saliva, blood and fecal samples following metformin treatment.
DESIGN: An, 18 week, one-armed cross over intervention trial consisting of a 6-week pre-intervention period, 6-week intervention period and a 6-week post-intervention period. 25 healthy young men will be included in the trial.
INTERVENTION: Six-week Metformin treatment to young healthy men.
Detailed description
An, 18 weeks, one-armed cross over intervention trial consisting of a 6-weeks pre-intervention period, 6-weeks intervention period and a 6-weeks post-intervention period. 25 healthy young men will be included in the trial. The pre-intervention period is the control period with no treatment. During the intervention period participants will receive 500 mg of metformin once daily the 1st week, then 500 mg twice daily the 2nd week, 1000 mg + 500 mg daily the 3rd week and 1000 mg + 1000 mg daily the remaining three weeks. Post-interventional investigators will examine gut microbiota of the participants 6 weeks after completion of the intervention period.
MESUREMENTS: Altered composition of gut microbiota as investigated by 16S rRNA sequencing is the primary outcome of this study. Secondary outcomes are to investigate changes in metabolic and inflammatory markers in blood and fecal samples. Blood, urine, saliva and fecal samples will be stored for future studies.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: Metformin18 weeks study with intervention during week 6 to 12: the intervention consist of 500 mg of metformin once daily for week 7, then 500 mg twice daily week 8, 1000 mg + 500 mg daily week 9 and 1000 mg + 1000 mg daily for weeks 10-12. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male
- HbA1c < 5.7 % (39 mmol/mol)
- Caucasian (self-report of parental ethnicity)
- Weight stabile with 18.5 kg/m2 < BMI < 27.0 kg/m2
- Normal kidney function as evaluated by normal p-creatinine for age
Key exclusion criteria (6 listed)
- Oral intake of any form of prescribed medication two months prior to recruitment
- Chronic or acute illness
- Previous gastro-intestinal operation excluding appendicitis
- Any other significant medical reason for exclusion as determined by the investigator
- Unable to give informed consent
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 |
|---|---|---|
| Metformin | Drug | Metformin |
Primary outcome
Structural changes in the human gut microbiota.
Time frame: Baseline, 4 , 7, 8, 10, 11 , 13, 16, and 18 weeks
Fecal samples are collected in order to characterize the gut microbiota composition. Microbial DNA will be subjected to sequencing, microbial gene analyses, including taxonomic and functional annotation.
14 secondary outcomes
Changes in plasma glucose and HbA1c levels
Time frame: Baseline and at week 7,10,13 and 18
Changes in insulin metabolism
Time frame: Baseline and at week 7,10,13 and 18
Changes in inflammatory markers in blood samples.
Time frame: Baseline and at week 7,10,13 and 18
Changes in kidney function tests.
Time frame: Baseline and at week 7,10,13 and 18
Changes in liver function tests.
Time frame: Baseline and at week 7,10,13 and 18
Serum Cobalamin
Time frame: Baseline and at week 7,10,13 and 18
Metformin plasma level
Time frame: At week 10 and 13.
Blood pressure
Time frame: Baseline and at week 7,13 and 18
Heart rate
Time frame: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Time frame: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Time frame: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Time frame: Baseline and at week 7,13 and 18
Bio-electrical impedance.
Time frame: Baseline and at week 7,13 and 18
GI symptoms
Time frame: Baseline and at week 7, 10, 13 and 18.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- Derived from this study: PubMed 30904939Bryrup T, Thomsen CW, Kern T, Allin KH, Brandslund I, Jorgensen NR, Vestergaard H, Hansen T, Hansen TH, Pedersen O, Nielsen T. Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study. Diabetologia. 2019 Jun;62(6):1024-1035. doi: 10.1007/s00125-019-4848-7. Epub 2019 Mar 23.
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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.
Oluf Pedersen, MD, Professor principal investigator
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin in people with Healthy, run by Oluf Borbye Pedersen at 1 site in Denmark.
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 5 inclusion and 6 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: finished, as of the sponsor's last update on 17 Feb 2016. 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 Denmark. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Structural changes in the human gut microbiota. (time frame: Baseline, 4 , 7, 8, 10, 11 , 13, 16, and 18 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02546050, which also lists 1 linked publication.
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 17 Feb 2016.