Clinical trial NCT02546050: The Effect of Metformin on Composition of Human Gut Bacteria
Official title: Effects of Metformin on Human Gut Microbiota
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Gut microbiota
metformin
Metabolism
Metagenomics
Metabolomics
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
First posted: 2015-09-10
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Structural changes in the human gut microbiota.
timeFrame: Baseline, 4 , 7, 8, 10, 11 , 13, 16, and 18 weeks
Secondary outcomes:
measure: Changes in plasma glucose and HbA1c levels
timeFrame: Baseline and at week 7,10,13 and 18
measure: Changes in insulin metabolism
timeFrame: Baseline and at week 7,10,13 and 18
measure: Changes in inflammatory markers in blood samples.
timeFrame: Baseline and at week 7,10,13 and 18
measure: Changes in kidney function tests.
timeFrame: Baseline and at week 7,10,13 and 18
measure: Changes in liver function tests.
timeFrame: Baseline and at week 7,10,13 and 18
measure: Serum Cobalamin
timeFrame: Baseline and at week 7,10,13 and 18
measure: Metformin plasma level
timeFrame: At week 10 and 13.
measure: Blood pressure
timeFrame: Baseline and at week 7,13 and 18
measure: Heart rate
timeFrame: Baseline and at week 7,13 and 18
measure: Anthropometrics characteristics
timeFrame: Baseline and at week 7,13 and 18
measure: Anthropometrics characteristics
timeFrame: Baseline and at week 7,13 and 18
measure: Anthropometrics characteristics
timeFrame: Baseline and at week 7,13 and 18
measure: Bio-electrical impedance.
timeFrame: Baseline and at week 7,13 and 18
measure: GI symptoms
timeFrame: Baseline and at week 7, 10, 13 and 18.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: The Novo Nordisk Foundation Center of Basic Metabolic Research, Section for Metabolic Genetics, University of Copenhagen
state: Copenhagen Ø
Study officials:
affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen
name: Oluf Pedersen, MD, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.