Clinical trial NCT03442972: Glucagon-like Peptide-2 Mediated Secretion of Stored Enteral Lipids
Official title: Investigating the Release of Stored Enteral Lipids in Response to a Single Subcutaneous Dose of Analogue Glucagon-like Peptide-2 in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hyperlipidemias
Keywords: Intestinal lipoprotein
Duodenal biopsy
Gut Peptide
Chylomicrons
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Kensington Screening Clinic
First posted: 2018-02-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to receive either teduglutide or placebo as a single subcutaneous injection, 1 hour prior to duodenal biopsy
Primary purpose: BASIC_SCIENCE

Brief summary: Some of the fat (triglyceride) from the food humans eat gets stored in the bowel. This triglyceride can then be released into the blood when another meal is consumed or in response to hormones. How the gut hormone glucagon-like peptide-2 (GLP-2) releases the triglyceride from the gut is not known. The research team in this study is interested in finding out how teduglutide (a degradation resistant form of GLP-2) releases stored triglyceride from the gut by studying samples from patients undergoing endoscopy and small bowel biopsy.

Detailed description: The release of stored enteral lipids will be investigated in 30 patients undergoing upper gastrointestinal endoscopy and duodenal biopsy for clinical indications. Patients undergoing the procedure will be recruited. Participants will have a high fat liquid meal as breakfast. 5 hours later, participants will be randomly assigned to receive either a subcutaneous injection of placebo (n=15) or a subcutaneous injection of the Health Canada approved glucagon-like peptide-2 (GLP-2) analogue (teduglutide, Revestive®, Shire Canada)(n=15 different subjects). 1 hour later, a duodenal biopsy specimen will be obtained from 2-3 sample sites,snap frozen in dry ice and stored at -80°C for further analysis.

Eligibility criteria: Inclusion Criteria:

* Men and women, aged 18 to 60 years requiring endoscopy and duodenal biopsies for clinical indications, with no contraindications to the procedure, as judged by Dr. Bookman of the Kensington Screening Clinic, Toronto, ON, Canada

Exclusion Criteria:

* Patients with active inflammatory bowel disease
* Patients with pre-existing Celiac disease, exocrine pancreatic insufficiency or small bowel malabsorption
* Patients with active bowel malignancy
* Patients with diabetes mellitus or known/ suspected motility disorders of the gut
* Patients with decompensated liver disease
* Patients on ezetimibe or bile acid sequestrants
* Patients who are pregnant or breastfeeding.
* Patients with renal disease
* Patients on benzodiazepine
* Unstable cardiac or respiratory disease
* Any changes to medication in the preceding month

Primary outcomes:
measure: Release of enteral lipids in response to teduglutide
timeFrame: 6 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hopital
state: Ontario
city: Toronto
country: Canada
facility: Kensington Screening Clinic
state: Ontario
Study officials:
affiliation: UHN
name: Gary F Lewis, MD
role: PRINCIPAL_INVESTIGATOR
References: