Regulation of Intestinal and Hepatic Lipoprotein Production by Glucagon Like Peptide 2

Regulation of Intestinal and Hepatic Lipoprotein Production by Glucagon Like

1. To assess whether Glucagon like peptide 2 (GLP-2) affects lipoprotein production (study A)
2. To assess whether GLP-2 affects the release of preformed chylomicrons (study B)

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: Placebo; Drug: GLP-2

Detailed Description

Study A: Using constant feeding with a nasoduodenal tube and stable isotope infusion, mathematical modelling will be utilised to measure lipoprotein production and clearance. The lipoproteins assessed will be apoB-100 from the liver and apoB-48 from the intestine.

StudyB: Volunteers will be given a liquid meal with retinyl palmitate (vitamin A) to label chylomicrons made from the meal. 7 hours later they will be given GLP-2 or placebo. Measurements of plasma and TRL(triglyceride rich lipoprotein) triglyceride and TRL retinyl palmitate will be carried out to see whether GLP-2 increases these parameters.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1L7
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inclusion Criteria:

  1. Men and women, aged 18 to 60 years
  2. Body mass index 20 kg/m2 to 30 kg/m2
  3. Hemoglobin above 130g/L.
  4. Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test (OGTT)

Exclusion Criteria:

• 1. Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.

  2. Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 100 or systolic > 180) or proliferative retinopathy 3. History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance.

  4. Any history of ischemic heart disease or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.

  5. Abnormal liver or thyroid function tests 6. Current addiction to alcohol or substances of abuse as determined by the investigator.

  7. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation 8. Taking any prescription or non-prescription medications at the time of the study 9. Having donated blood three months prior to and three months post study procedures 10. A pregnancy test will be performed 1 to 3 days prior to each study in all female research participants. Those who test positive for pregnancy will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo
Experimental: GLP=2; active treatment with a single dose of GLP-2 (1500mcg)	Drug: GLP-2; single subcutaneous dose of 1500mcg; Other Names: glucagon like peptide 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipoprotein production and clearance rate	ApoB 100 and ApoB 48 production and clearance	10 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and TRL triglyceride and TRL retinyl palmitate	Measurements will be carried out hourly after ingestion of meal and then every 15-30 minutes thereafter to see if GLP-2 increases these parameters compared to placebo.	10 hours

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Publications and helpful links

General Publications

• Dash S, Xiao C, Morgantini C, Connelly PW, Patterson BW, Lewis GF. Glucagon-like peptide-2 regulates release of chylomicrons from the intestine. Gastroenterology. 2014 Dec;147(6):1275-1284.e4. doi: 10.1053/j.gastro.2014.08.037. Epub 2014 Aug 28.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: October 8, 2013
• First Posted (Estimate): October 9, 2013

Study Record Updates

• Last Update Posted (Estimate): March 10, 2015
• Last Update Submitted That Met QC Criteria: March 6, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Lipoproteins, apoB, GLP-2
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: REB-07-0394