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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
26
The Novo Nordisk Foundation Center of Basic Metabolic Research, Section for Metabolic Genetics, University of Copenhagen
Copenhagen, Copenhagen Ø, Denmark
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.
Time frame: Baseline, 4 , 7, 8, 10, 11 , 13, 16, and 18 weeks
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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: Baseline and at week 7,10,13 and 18
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Serum Cobalamin
Venous blood will be collected. The samples will be analyzed for serum cobalamin and correlated to gut microbiota changes
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Weight is measured using standardized procedures.
Time frame: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Height is measured using standardized procedures.
Time frame: Baseline and at week 7,13 and 18
Anthropometrics characteristics
Waist- and hip circumference are measured using standardized procedures.
Time frame: Baseline and at week 7,13 and 18
Bio-electrical impedance.
Body composition will be measured through bio-electrical impedance
Time frame: 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.
Time frame: Baseline and at week 7, 10, 13 and 18.