Clinical trial NCT03018444: The Effect of HMG-CoA Reductase Inhibition on Postprandial GLP-1 Secretion
Official title: The Effect of HMG-CoA Reductase Inhibition on Postprandial GLP-1 Secretion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2017-01-12
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of the present study is to evaluate the effect of HMG-CoA reductase inhibition during 14 days on the postprandial plasma GLP-1 response in healthy individuals. Secondary objectives include the evaluation of HMG-CoA reductase inhibition on postprandial glucose tolerance, gallbladder emptying, gastric emptying, plasma responses of lipids, bile acids and pancreatic and enteric hormones known to influence glucose metabolism and appetite, and faecal content of bile acids and gut microbiota composition.


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) \>18.5 kg/m2 and \<35 kg/m2
* Caucasian ethnicity
* Normal haemoglobin
* Glycated haemoglobin (HbA1c) \<43 mmol/mol
* Fasting plasma glucose \<6 mmol/l
* Informed and written consent

Exclusion Criteria:

* Diabetes
* First-degree relatives with diabetes (both type 1 diabetes and type 2 diabetes)
* Liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2 times normal values) or history of hepatobiliary disorder
* Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
* Reduced kidney function or nephropathy (estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73 m2 (based on serum creatinine) and/or albuminuria
* Taking any kind of medicine on a regular basis
* Intake of antibiotics two months prior to study
* Active or recent malignant disease
* Any treatment or condition requiring acute or sub-acute medical or surgical intervention
* Any condition considered incompatible with participation by the investigators
* If the subjects receive any antibiotic treatment while included in the study they will be excluded

Primary outcomes:
measure: Postprandial GLP-1 secretion
timeFrame: 240 min
Secondary outcomes:
measure: Postprandial Bile Acid Composition
timeFrame: 240 min
measure: Postprandial total plasma Bile Acid
timeFrame: 240 min
measure: Postprandial Glucose Tolerance
timeFrame: 240 min
measure: Postprandial plasma lipid response
timeFrame: 240 min
measure: Postprandial GIP secretion
timeFrame: 240 min
measure: Enteric hormones known to influence glucose metabolism
timeFrame: 240 min
measure: Gallbladder emptying
timeFrame: 240 min
measure: Faecal content of bile acid
timeFrame: One sample collected on day 12 or 13 of the intervention
measure: Gut microbiota composition
timeFrame: One sample collected on day 12 or 13 of the intervention
measure: Gastric emptying
timeFrame: 240 min
measure: Resting Energy Expenditure
timeFrame: At time -20 min, +60 min and +220 min
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: University Hospital, Gentofte, Copenhagen
state: Region Hovedstaden
Study officials:
affiliation: Department of Clinical Medicine, University of Copenhagen, Gentofte Hospital
name: Filip K. Knop, Professor MD
role: PRINCIPAL_INVESTIGATOR
References: