The Effect of Metformin on Composition of Human Gut Bacteria

• Sponsor: Oluf Borbye Pedersen (Other)
• Overall Status: Completed
• CT.gov ID: NCT02546050
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arm: 1
• Duration (Months): 8
• Patients Per Site Per Month: 3.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Metformin	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of Metformin on Human Gut Microbiota
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin 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.	Drug: Metformin

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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.

3. 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.

4. 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

5. 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

6. 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

7. 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

8. 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.

9. 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.

10. Anthropometrics characteristics [Baseline and at week 7,13 and 18]

    Weight is measured using standardized procedures.

11. Anthropometrics characteristics [Baseline and at week 7,13 and 18]

    Height is measured using standardized procedures.

12. Anthropometrics characteristics [Baseline and at week 7,13 and 18]

    Waist- and hip circumference are measured using standardized procedures.

13. Bio-electrical impedance. [Baseline and at week 7,13 and 18]

    Body composition will be measured through bio-electrical impedance

14. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Novo Nordisk Foundation Center of Basic Metabolic Research, Section for Metabolic Genetics, University of Copenhagen	Copenhagen	Copenhagen Ø	Denmark	2100

Sponsors and Collaborators

• Oluf Borbye Pedersen

Investigators

• Principal Investigator: Oluf Pedersen, MD, Professor, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Oluf Borbye Pedersen, Director, Professor, dr.med, University of Copenhagen
• ClinicalTrials.gov Identifier: NCT02546050
• Other Study ID Numbers: NNF-CBMR 2015-000199-86; 2015-000199-86
• First Posted: Sep 10, 2015
• Last Update Posted: Feb 17, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Oluf Borbye Pedersen, Director, Professor, dr.med, University of Copenhagen: Gut microbiota; metformin; Metabolism; Metagenomics; Metabolomics
• Additional relevant MeSH terms: Metformin

Study Results

No Results Posted as of Feb 17, 2016