Eradication of Gut Microbiota

Obesity Clinical Trial

— ERA  

Official title:

Eradication of Gut Microbiota - Effects on Postprandial Gut Hormone Secretion, Glucose Metabolism, Bone Metabolism and Gut Microbiome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01633762
• Other study ID #: ERA 2012
• Status: Completed
• Phase: Phase 0
• First received: June 28, 2012
• Last updated: November 30, 2015
• Start date: April 2012
• Est. completion date: April 2013

Study information

• Verified date: November 2015
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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)

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes
• Inflammation
• Obesity
• Osteoporosis

Intervention

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)

Locations

Country	Name	City	State
Denmark	Gentofte University Hospital	Hellerup

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	Department of clinical microbiology, Rigshospitalet, Copenhagen, Steno Diabetes Center, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	changes in postprandial insulin/c-peptide secretion	plasma level of insulin/C-peptide at baseline and during a 4 hour-meal test	0, 4 and 42 days after antibiotic eradication of gut bacteria	No
Secondary	changes in postprandial glucose levels	plasma level of glucose at baseline and during a 4 hour-meal test	0, 4 and 42 days after antibiotic eradication of gut bacteria	No
Secondary	changes in postprandial GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin secretion	plasma levels of GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin at baseline and during a 4 hour-meal test	0, 4 and 42 days after antibiotic eradication of gut bacteria	No
Secondary	changes in markers of bone formation and resorption	fasting plasma levels of osteocalcin, P1NP, CTX, 1CTP, sklerostin and serotonin	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	gut microbiome composition	faecal bacterial composition determined from microbiological cultures and deep metagenomic next-generation sequencing of bacterial DNA in feces	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	changes in markers of systemic inflammation	plasma levels of high sensitive CRP, LPBP, TNF-alfa, IL-6 and PAI	0, 4, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	changes in glycated hemoglobin (HbA1c)	plasma level of glycated hemoblobin	42 days after antibiotic eradication of gut bacteria	No
Secondary	changes in body weight		0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	changes in basal metabolic rate and respiratory quotient	indirect calorimetry measurements (210 minutes postprandial)	0, 4 and 42 days after antibiotic eradication of gut bacteria	No
Secondary	changes in gastric emptying	1,5 grams of paracetamol will be added to a standardized meal, plasma paracetamol will be measured at baseline and succeeding 4 hours postprandial	0, 4 and 42 days after antibiotic eradication of gut bacteria	No
Secondary	changes in gall bladder emptying	ultrasonic determination of gall bladder dimensions at baseline and during a 4 hour-meal test (expressed as gall bladder ejection fraction)	0, 4 and 42 days after antibiotic eradication of gut bacteria	No
Secondary	appetite, satiety and food intake	the impact of eradication on alimentary processes and appetite regulation will be measured using questionnaires and food intake measures	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	changes in ketone metabolism	measurement of fasting plasma beta-hydroxybutyrate level	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	changes in bile acid deconjugation	measurement of feces bile acid (conjugated and deconjugated) concentration to study the effect of gut microbiome presence on bile acid deconjugation	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	changes in plasma lipid levels	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)	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	microbiome in blood, urine and saliva	measurements on bacteria or bacterial components in blood, urine and saliva to study the effects of gut eradication on blood, urine and saliva microbiome	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No
Secondary	adverse effects of the used antibiotics	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.	up to 180 days after antibiotic eradication of gut bacteria	Yes
Secondary	changes in metabolomic profile	plasma and urine samples for metabolomic analysis	0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria	No