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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000199-86 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, 4 , 7, 8, 10, 11 , 13, 16, and 18 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline and at week 7,10,13 and 18 |
| Changes in insulin metabolism |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Oluf Pedersen, MD, Professor | The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Novo Nordisk Foundation Center of Basic Metabolic Research, Section for Metabolic Genetics, University of Copenhagen | Copenhagen | Copenhagen Ø | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30904939 | Derived | 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. |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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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. |
| 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. | 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 | 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 | 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 | 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 | 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. | 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. | Baseline and at week 7,13 and 18 |
| Anthropometrics characteristics | Weight is measured using standardized procedures. | Baseline and at week 7,13 and 18 |
| Anthropometrics characteristics | Height is measured using standardized procedures. | Baseline and at week 7,13 and 18 |
| Anthropometrics characteristics | Waist- and hip circumference are measured using standardized procedures. | Baseline and at week 7,13 and 18 |
| Bio-electrical impedance. | Body composition will be measured through bio-electrical impedance | 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. | Baseline and at week 7, 10, 13 and 18. |