The Effect of Metformin on Composition of Human Gut Bacteria

Healthy Clinical Trial

Official title:

Effects of Metformin on Human Gut Microbiota

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02546050
• Other study ID #: NNF-CBMR 2015-000199-86
• Secondary ID: 2015-000199-86
• Status: Completed
• Phase: Phase 1
• First received: July 1, 2015
• Last updated: February 16, 2016
• Start date: June 2015
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines AuthorityDenmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Metformin

Locations

Country	Name	City	State
Denmark	The Novo Nordisk Foundation Center of Basic Metabolic Research, Section for Metabolic Genetics, University of Copenhagen	Copenhagen	Copenhagen Ø

Sponsors (1)

Lead Sponsor	Collaborator
Oluf Borbye Pedersen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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.	Baseline and at week 7,10,13 and 18	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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.	No
Secondary	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	No
Secondary	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	No
Secondary	Anthropometrics characteristics	Weight is measured using standardized procedures.	Baseline and at week 7,13 and 18	No
Secondary	Anthropometrics characteristics	Height is measured using standardized procedures.	Baseline and at week 7,13 and 18	No
Secondary	Anthropometrics characteristics	Waist- and hip circumference are measured using standardized procedures.	Baseline and at week 7,13 and 18	No
Secondary	Bio-electrical impedance.	Body composition will be measured through bio-electrical impedance	Baseline and at week 7,13 and 18	No
Secondary	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.	No