Eradication of Gut Microbiota (ERA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Copenhagen
Steno Diabetes Center
Department of clinical microbiology, Rigshospitalet, Copenhagen
Information provided by (Responsible Party):
Kristian Hallundbuk Mikkelsen, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01633762
First received: June 28, 2012
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Diabetes
Obesity
Osteoporosis
Inflammation
Drug: meropenem, gentamicin, vancomycin (together)
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Eradication of Gut Microbiota - Effects on Postprandial Gut Hormone Secretion, Glucose Metabolism, Bone Metabolism and Gut Microbiome

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • changes in postprandial GLP-1 secretion [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    plasma level of GLP-1 at baseline and during a 4 hour-meal test


Secondary Outcome Measures:
  • changes in postprandial insulin/c-peptide secretion [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    plasma level of insulin/C-peptide at baseline and during a 4 hour-meal test

  • changes in postprandial glucose levels [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    plasma level of glucose at baseline and during a 4 hour-meal test

  • changes in postprandial GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin secretion [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    plasma levels of GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin at baseline and during a 4 hour-meal test

  • changes in markers of bone formation and resorption [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    fasting plasma levels of osteocalcin, P1NP, CTX, 1CTP, sklerostin and serotonin

  • gut microbiome composition [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    faecal bacterial composition determined from microbiological cultures and deep metagenomic next-generation sequencing of bacterial DNA in feces

  • changes in markers of systemic inflammation [ Time Frame: 0, 4, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    plasma levels of high sensitive CRP, LPBP, TNF-alfa, IL-6 and PAI

  • changes in glycated hemoglobin (HbA1c) [ Time Frame: 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    plasma level of glycated hemoblobin

  • changes in body weight [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
  • changes in basal metabolic rate and respiratory quotient [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    indirect calorimetry measurements (210 minutes postprandial)

  • changes in gastric emptying [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    1,5 grams of paracetamol will be added to a standardized meal, plasma paracetamol will be measured at baseline and succeeding 4 hours postprandial

  • changes in gall bladder emptying [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    ultrasonic determination of gall bladder dimensions at baseline and during a 4 hour-meal test (expressed as gall bladder ejection fraction)

  • appetite, satiety and food intake [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    the impact of eradication on alimentary processes and appetite regulation will be measured using questionnaires and food intake measures

  • changes in ketone metabolism [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    measurement of fasting plasma beta-hydroxybutyrate level

  • changes in bile acid deconjugation [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    measurement of feces bile acid (conjugated and deconjugated) concentration to study the effect of gut microbiome presence on bile acid deconjugation

  • changes in plasma lipid levels [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    fasting plasma levels of triglyceride, VLDL, LDL, HDL, total cholesterol, in addition: measurements of free fatty acids during a 4 hour meal 0, 4 and 42 days after eradication (not on day 8 and 180)

  • microbiome in blood, urine and saliva [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    measurements on bacteria or bacterial components in blood, urine and saliva to study the effects of gut eradication on blood, urine and saliva microbiome

  • adverse effects of the used antibiotics [ Time Frame: up to 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: Yes ]
    standardized questionaries regarding gastointestinal function are filled out at each study visit (0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria) to detect possible adverse effects of antibiotics. In addition, subjects are given a calendar and informed to write down any symptom or illness during the study period.

  • changes in metabolomic profile [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ] [ Designated as safety issue: No ]
    plasma and urine samples for metabolomic analysis


Enrollment: 12
Study Start Date: April 2012
Estimated Study Completion Date: February 2016
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: meropenem, gentamicin, vancomycin Drug: meropenem, gentamicin, vancomycin (together)
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)

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01633762

Locations
Denmark
Gentofte University Hospital
Hellerup, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
University of Copenhagen
Steno Diabetes Center
Department of clinical microbiology, Rigshospitalet, Copenhagen
Investigators
Study Director: Kristian H Mikkelsen, MD Diabetes Research Unit, Gentofte Hospital
  More Information

No publications provided

Responsible Party: Kristian Hallundbuk Mikkelsen, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01633762     History of Changes
Other Study ID Numbers: ERA 2012
Study First Received: June 28, 2012
Last Updated: July 1, 2013
Health Authority: Denmark: Danish Dataprotection Agency

Additional relevant MeSH terms:
Inflammation
Osteoporosis
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Pathologic Processes
Gentamicins
Meropenem
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014