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Eradication of Gut Microbiota (ERA)

This study has been completed.
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: November 30, 2015
Last verified: November 2015
History of Changes

June 28, 2012
November 30, 2015
April 2012
April 2013   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01633762 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Eradication of Gut Microbiota
Eradication of Gut Microbiota - Effects on Postprandial Gut Hormone Secretion, Glucose Metabolism, Bone Metabolism and Gut Microbiome
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.
Not Provided
Interventional
Phase 0
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
  • Diabetes
  • Obesity
  • Osteoporosis
  • Inflammation
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)
Experimental: meropenem, gentamicin, vancomycin
Intervention: Drug: meropenem, gentamicin, vancomycin (together)
Mikkelsen KH, Frost M, Bahl MI, Licht TR, Jensen US, Rosenberg J, Pedersen O, Hansen T, Rehfeld JF, Holst JJ, Vilsbøll 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
April 2013
April 2013   (final data collection date for primary outcome measure)

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)
Male
18 Years to 40 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT01633762
ERA 2012
No
Not Provided
Not Provided
Kristian Hallundbuk Mikkelsen, University Hospital, Gentofte, Copenhagen
University Hospital, Gentofte, Copenhagen
  • University of Copenhagen
  • Steno Diabetes Center
  • Department of clinical microbiology, Rigshospitalet, Copenhagen
Study Director: Kristian H Mikkelsen, MD Diabetes Research Unit, Gentofte Hospital
University Hospital, Gentofte, Copenhagen
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP