Healthy
Conditions
Keywords
Gut microbiota, metformin, Metabolism, Metagenomics, Metabolomics
Brief 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. 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.
Interventions
DRUGMetformin
Sponsors
Oluf Borbye Pedersen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Structural changes in the human gut microbiota. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in insulin metabolism | Baseline and at week 7,10,13 and 18 | 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. |
| Changes in inflammatory markers in blood samples. | Baseline and at week 7,10,13 and 18 | Venous blood will be collected. The samples will be analyzed for markers of inflammation such as high sensitive C-reactive protein. |
| Changes in kidney function tests. | Baseline and at week 7,10,13 and 18 | Venous blood will be collected. The samples will be analyzed for plasma creatinine and correlated to gut microbiota changes |
| Changes in liver function tests. | Baseline and at week 7,10,13 and 18 | Venous blood will be collected. The samples will be analyzed for liver function test and correlated to gut microbiota changes |
| Serum Cobalamin | Baseline and at week 7,10,13 and 18 | Venous blood will be collected. The samples will be analyzed for serum cobalamin and correlated to gut microbiota changes |
| Changes in plasma glucose and HbA1c levels | Baseline and at week 7,10,13 and 18 | Venous blood will be collected. The samples will be analyzed for plasma glucose and HbA1c, and correlated to changes in gut microbiota composition |
| Blood pressure | Baseline and at week 7,13 and 18 | 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. |
| Heart rate | Baseline and at week 7,13 and 18 | 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. |
| Anthropometrics characteristics | Baseline and at week 7,13 and 18 | Weight is measured using standardized procedures. |
| Bio-electrical impedance. | Baseline and at week 7,13 and 18 | Body composition will be measured through bio-electrical impedance |
| GI symptoms | Baseline and at week 7, 10, 13 and 18. | 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. |
| Metformin plasma level | At week 10 and 13. | 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 |
Countries
Denmark
Outcome results
None listed