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Eradication of Gut Microbiota (ERA)

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ClinicalTrials.gov Identifier: NCT01633762
Recruitment Status : Completed
First Posted : July 4, 2012
Last Update Posted : December 2, 2015
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Diabetes Obesity Osteoporosis Inflammation Drug: meropenem, gentamicin, vancomycin (together) Early Phase 1

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : April 2012
Primary Completion Date : April 2013
Study Completion Date : April 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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)


Outcome Measures

Primary Outcome Measures :
  1. changes in postprandial GLP-1 secretion [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ]
    plasma level of GLP-1 at baseline and during a 4 hour-meal test


Secondary Outcome Measures :
  1. changes in postprandial insulin/c-peptide secretion [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ]
    plasma level of insulin/C-peptide at baseline and during a 4 hour-meal test

  2. changes in postprandial glucose levels [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ]
    plasma level of glucose at baseline and during a 4 hour-meal test

  3. 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 ]
    plasma levels of GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin at baseline and during a 4 hour-meal test

  4. changes in markers of bone formation and resorption [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    fasting plasma levels of osteocalcin, P1NP, CTX, 1CTP, sklerostin and serotonin

  5. gut microbiome composition [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    faecal bacterial composition determined from microbiological cultures and deep metagenomic next-generation sequencing of bacterial DNA in feces

  6. changes in markers of systemic inflammation [ Time Frame: 0, 4, 42 and 180 days after antibiotic eradication of gut bacteria ]
    plasma levels of high sensitive CRP, LPBP, TNF-alfa, IL-6 and PAI

  7. changes in glycated hemoglobin (HbA1c) [ Time Frame: 42 days after antibiotic eradication of gut bacteria ]
    plasma level of glycated hemoblobin

  8. changes in body weight [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
  9. changes in basal metabolic rate and respiratory quotient [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ]
    indirect calorimetry measurements (210 minutes postprandial)

  10. changes in gastric emptying [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ]
    1,5 grams of paracetamol will be added to a standardized meal, plasma paracetamol will be measured at baseline and succeeding 4 hours postprandial

  11. changes in gall bladder emptying [ Time Frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria ]
    ultrasonic determination of gall bladder dimensions at baseline and during a 4 hour-meal test (expressed as gall bladder ejection fraction)

  12. appetite, satiety and food intake [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    the impact of eradication on alimentary processes and appetite regulation will be measured using questionnaires and food intake measures

  13. changes in ketone metabolism [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    measurement of fasting plasma beta-hydroxybutyrate level

  14. changes in bile acid deconjugation [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    measurement of feces bile acid (conjugated and deconjugated) concentration to study the effect of gut microbiome presence on bile acid deconjugation

  15. changes in plasma lipid levels [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    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)

  16. microbiome in blood, urine and saliva [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    measurements on bacteria or bacterial components in blood, urine and saliva to study the effects of gut eradication on blood, urine and saliva microbiome

  17. adverse effects of the used antibiotics [ Time Frame: up to 180 days after antibiotic eradication of gut bacteria ]
    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.

  18. changes in metabolomic profile [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]
    plasma and urine samples for metabolomic analysis


Eligibility Criteria

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kristian Hallundbuk Mikkelsen, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01633762     History of Changes
Other Study ID Numbers: ERA 2012
First Posted: July 4, 2012    Key Record Dates
Last Update Posted: December 2, 2015
Last Verified: November 2015

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