Eradication of Gut Microbiota

NCT01633762 | Completed Early Phase 1

• 1 other identifier: ERA 2012
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to assess the effect of eradication of gut microbiota on 1) glucose metabolism including postprandial plasma responses of the incretin hormones GIP and GLP-1, insulin, C-peptide and glucagon, 2) metabolomic profiles and resting energy expenditure (REE) 3) appetite, satiety, food intake, gastric emptying and gall bladder emptying, 4) levels of markers of bone formation and resorption as well as serotonin, 5) markers of systemic inflammation, and 6) on the (prospective) composition of bacteria in faeces, blood and saliva. Thus, the overall objective is to provide detailed knowledge on the physiological role of gut microbiota combined with bioinformatic analyses of the functional implications of changes in bacteria composition on the level of both species and phylum.

Conditions

Diabetes; Obesity; Osteoporosis; Inflammation

Outcome Measures

Primary Outcomes (1)

• changes in postprandial GLP-1 secretion

  plasma level of GLP-1 at baseline and during a 4 hour-meal test

  0, 4 and 42 days after antibiotic eradication of gut bacteria

Secondary Outcomes (18)

• changes in postprandial insulin/c-peptide secretion

  0, 4 and 42 days after antibiotic eradication of gut bacteria

• changes in postprandial glucose levels

  0, 4 and 42 days after antibiotic eradication of gut bacteria

• changes in postprandial GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin secretion

  0, 4 and 42 days after antibiotic eradication of gut bacteria

• changes in markers of bone formation and resorption

  0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria

• gut microbiome composition

  0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria

Study Arms (1)

meropenem, gentamicin, vancomycin

EXPERIMENTAL

Drug: meropenem, gentamicin, vancomycin (together)

Interventions

meropenem, gentamicin, vancomycin (together) DRUG

4 days antibiotic treatment, per oral, once daily: vancomycin 500 mg (Vancomycin "Hospira"), powder for concentrate; gentamycin 40 mg ("Hexamycin®"), solution; meropenem 500 mg (Meropenem "Hospira"), powder for concentrate; The three drugs are dissolved and combined to a cocktail (with approximately 100 ml of apple juice)

meropenem, gentamicin, vancomycin

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• danish caucasian ethnicity
• informed consent
• normal fasting plasma glucose
• normal HbA1c (\<6 %)
• normal serum lipids
• normal thyroid function
• normal danish diet
• non-smoking
• normal stool habits

You may not qualify if:

• known bone disease
• liver disease (ALAT or ASAT \>2 upper normal value)
• kidney disease (serum creatinine \>130 μM)
• anaemia
• BMI \<18.5 kg/m2 or BMI \>25 kg/m2
• known gastrointestinal disease (including prior bariatric surgery,lactose -intolerance, celiac disease, inflammatory bowel disease) or known familial disposition for lactose intolerance, celiac disease, inflammatory bowel disease
• antibiotic treatment within 6 months prior to study including malaria prophylaxis
• medication which cannot be on hold for the study period
• contraindications against/allergy towards the used antibiotics (including prior allergic reactions related to beta-lactam antibiotics, aminoglycosides or vancomycin)

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• University of Copenhagen: collaborator
• Steno Diabetes Center Copenhagen: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Gentofte University Hospital

Hellerup, 2900, Denmark

Location

Related Publications (1)

• Mikkelsen KH, Frost M, Bahl MI, Licht TR, Jensen US, Rosenberg J, Pedersen O, Hansen T, Rehfeld JF, Holst JJ, Vilsboll T, Knop FK. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism. PLoS One. 2015 Nov 12;10(11):e0142352. doi: 10.1371/journal.pone.0142352. eCollection 2015.

  PMID: 26562532 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Obesity; Osteoporosis; Inflammation

Interventions

Meropenem; Gentamicins; Vancomycin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Pathologic Processes

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Kristian H Mikkelsen, MD

  Diabetes Research Unit, Gentofte Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 28, 2012
• First Posted: July 4, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: December 2, 2015

Record last verified: 2015-11

Locations

DK (1)