Ignite Creation Date:
2025-12-24 @ 11:47 AM
Ignite Modification Date:
2026-03-27 @ 8:32 AM
Study NCT ID:
NCT03534661
Status:
COMPLETED
Last Update Posted:
2020-03-27
First Post:
2018-05-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
L-NMMA on GLP-2 Mediated Intestinal Lipoprotein Release
Sponsor:
University Health Network, Toronto
Organization:
Study Overview
Official Title:
Role of a Nitric Oxide Synthase Inhibitor on GLP-2 Mediated Intestinal Lipoprotein Release
Status:
COMPLETED
Status Verified Date:
2019-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LNMMA
Brief 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.
Detailed Description:
This is a single-blind, cross over, Phase 3b clinical study. The protocol aims to study 15 healthy, lean, non-diabetic males and females for three studies each, in random order, approximately four weeks apart, as follows.
Study A (L-NMMA + Teduglutide study): Volunteers will receive high-fat nutritional drink and seven hours later a subcutaneous injection of Teduglutide (0.05mg/kg of body weight, which is the FDA-approved route and daily dose for the treatment of short bowel syndrome).Thirty minutes prior to Teduglutide, the subject will receive an intravenous infusion of L-NMMA up to a maximum amount of 10 mg/kg, to inhibit nitric oxide synthesis. Lipid and lipoprotein levels will be measured at regular intervals for 3 hours following the injection of Teduglutide. Mesenteric blood flow will be measured at regular intervals by ultrasonography on some volunteers.
Study B (Teduglutide + normal saline): The design is identical to study A, except that, instead of L-NMMA, normal saline of the same volume will be infused.
Study C (Placebo + L-NMMA): The design is identical to study A, except that, instead of Teduglutide, a placebo will be injected subcutaneously.
Mesenteric Blood Flow measurement: Mesenteric blood flow will be measured at the bedside for some of the volunteers by ultrasonography in each study (A, B, C) before, during and after the administration of L-NMMA and Teduglutide. The first evaluation will begin 15 min before the start of the L-NMMA infusion and periodically afterwards.
Study A (L-NMMA + Teduglutide study): Volunteers will receive high-fat nutritional drink and seven hours later a subcutaneous injection of Teduglutide (0.05mg/kg of body weight, which is the FDA-approved route and daily dose for the treatment of short bowel syndrome).Thirty minutes prior to Teduglutide, the subject will receive an intravenous infusion of L-NMMA up to a maximum amount of 10 mg/kg, to inhibit nitric oxide synthesis. Lipid and lipoprotein levels will be measured at regular intervals for 3 hours following the injection of Teduglutide. Mesenteric blood flow will be measured at regular intervals by ultrasonography on some volunteers.
Study B (Teduglutide + normal saline): The design is identical to study A, except that, instead of L-NMMA, normal saline of the same volume will be infused.
Study C (Placebo + L-NMMA): The design is identical to study A, except that, instead of Teduglutide, a placebo will be injected subcutaneously.
Mesenteric Blood Flow measurement: Mesenteric blood flow will be measured at the bedside for some of the volunteers by ultrasonography in each study (A, B, C) before, during and after the administration of L-NMMA and Teduglutide. The first evaluation will begin 15 min before the start of the L-NMMA infusion and periodically afterwards.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: