Eradication of Gut Microbiota (ERA)

Tracking Information
First Submitted Date ICMJE	June 28, 2012
First Posted Date ICMJE	July 4, 2012
Last Update Posted Date	December 2, 2015
Study Start Date ICMJE	April 2012
Actual Primary Completion Date	April 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 29, 2012)	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
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01633762 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 29, 2012)	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; 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; 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; 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; 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; 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; changes in glycated hemoglobin (HbA1c) [ Time Frame: 42 days after antibiotic eradication of gut bacteria ]plasma level of glycated hemoblobin; changes in body weight [ Time Frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria ]; 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); 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; 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); 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; 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; 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; 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); 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; 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.; 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
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Eradication of Gut Microbiota
Official Title ICMJE	Eradication of Gut Microbiota - Effects on Postprandial Gut Hormone Secretion, Glucose Metabolism, Bone Metabolism and Gut Microbiome
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Early Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
Condition ICMJE	Diabetes; Obesity; Osteoporosis; Inflammation
Intervention ICMJE	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)
Study Arms	Experimental: meropenem, gentamicin, vancomycin; Intervention: Drug: meropenem, gentamicin, vancomycin (together)
Publications *	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.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 29, 2012)	12
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	April 2013
Actual Primary Completion Date	April 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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)
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years to 40 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Denmark
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01633762
Other Study ID Numbers ICMJE	ERA 2012
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Kristian Hallundbuk Mikkelsen, University Hospital, Gentofte, Copenhagen
Study Sponsor ICMJE	University Hospital, Gentofte, Copenhagen
Collaborators ICMJE	University of Copenhagen; Steno Diabetes Center; Department of clinical microbiology, Rigshospitalet, Copenhagen
Investigators ICMJE	Study Director: Kristian H Mikkelsen, MD Diabetes Research Unit, Gentofte Hospital
PRS Account	University Hospital, Gentofte, Copenhagen
Verification Date	November 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP