Clinical trial NCT01633762: Eradication of Gut Microbiota
Official title: Eradication of Gut Microbiota - Effects on Postprandial Gut Hormone Secretion, Glucose Metabolism, Bone Metabolism and Gut Microbiome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Diabetes
Obesity
Osteoporosis
Inflammation
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Steno Diabetes Center Copenhagen
name: Department of clinical microbiology, Rigshospitalet, Copenhagen
First posted: 2012-07-04
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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)

Primary outcomes:
measure: changes in postprandial GLP-1 secretion
timeFrame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
Secondary outcomes:
measure: changes in postprandial insulin/c-peptide secretion
timeFrame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
measure: changes in postprandial glucose levels
timeFrame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
measure: changes in postprandial GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin secretion
timeFrame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
measure: changes in markers of bone formation and resorption
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: gut microbiome composition
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: changes in markers of systemic inflammation
timeFrame: 0, 4, 42 and 180 days after antibiotic eradication of gut bacteria
measure: changes in glycated hemoglobin (HbA1c)
timeFrame: 42 days after antibiotic eradication of gut bacteria
measure: changes in body weight
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: changes in basal metabolic rate and respiratory quotient
timeFrame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
measure: changes in gastric emptying
timeFrame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
measure: changes in gall bladder emptying
timeFrame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
measure: appetite, satiety and food intake
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: changes in ketone metabolism
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: changes in bile acid deconjugation
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: changes in plasma lipid levels
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: microbiome in blood, urine and saliva
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
measure: adverse effects of the used antibiotics
timeFrame: up to 180 days after antibiotic eradication of gut bacteria
measure: changes in metabolomic profile
timeFrame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Gentofte University Hospital
Study officials:
affiliation: Diabetes Research Unit, Gentofte Hospital
name: Kristian H Mikkelsen, MD
role: STUDY_DIRECTOR
References:
citation: Mikkelsen KH, Frost M, Bahl MI, Licht TR, Jensen US, Rosenberg J, Pedersen O, Hansen T, Rehfeld JF, Holst JJ, Vilsboll 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.