L-NMMA on GLP-2 Mediated Intestinal Lipoprotein Release

• Status: Completed
• Trial end date: 2019-03-20
• Target enrollment: 0
• Participant gender: All

Summary

The gut is able to retain some fat for many hours after a fatty meal. The gut hormone glucagon-like peptide-2 (GLP-2) is known to release these fat stores in the gut, but it is not known how GLP-2 achieves this. One possibility is that GLP-2 increases blood flow in the gut. NG-monomethyl-L-arginine (L-NMMA) is a substance that inhibits nitric oxide synthase (an enzyme that helps make nitric oxide which increases blood flow). This protocol examines whether blocking gut blood flow with L-NMMA is able to prevent GLP-2 from releasing gut lipid stores. Healthy participants will be treated with a combination of Teduglutide (a resistant form of GLP-2) and L-NMMA, and their respective controls. Blood lipid levels will be measured following treatments.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Health Network, Toronto
• Treatments: omega-N-Methylarginine; Teduglutide

Criteria

Inclusion Criteria:

• Men and women, aged 18 to 60 years

• Body mass index 20 kg/m2 to 30 kg/m2

• Hemoglobin above 130g/L.

• Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test

Exclusion Criteria:

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

• Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (creatinine > 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic blood pressure > 100 or systolic > 180) or proliferative retinopathy

• History of diabetes or oral glucose tolerance indicative of diabetes or impaired glucose tolerance.

• Any history of a myocardial infarction or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on electrocardiogram, unstable angina, or decompensated heart failure.

• Any laboratory values: aspartate transaminase > 2x upper limit of normal; alanine aminotransferase > 2x upper limit of normal; thyroid-stimulating hormone > 6 miliunit/l

• Current addiction to alcohol or substances of abuse as determined by the investigator.

• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation

• Taking any prescription or non-prescription medications at the time of the study

• Having donated blood three months prior to and three months post study procedures

• 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.