Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03534661
Other study ID # L-NMMA 13-6415
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
Start date September 27, 2017
Est. completion date March 20, 2019

Study information

Verified date March 2019
Source University Health Network, Toronto
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 10
Est. completion date March 20, 2019
Est. primary completion date March 20, 2019
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 60 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Teduglutide + Normal Saline
Teduglutide 0.05 mg/kg subcutaneous injection; Normal Saline intravenous infusion
Teduglutide + L-NMMA
Teduglutide 0.05 mg/kg subcutaneous injection; L-NMMA 10 mg/kg intravenous infusion
Placebo + L-NMMA
Placebo subcutaneous injection; L-NMMA 10 mg/kg intravenous infusion

Locations

Country Name City State
Canada Tornto General Hospital, UHN Toronto Ontario

Sponsors (1)

Lead Sponsor Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Plasma Lipid Levels Lipid levels in plasma and lipoprotein fractions are measured following treatments 10.5 hours
Secondary Blood Flow Mesenteric blood flow rates are measured with ultrasound following treatments 3 hours
See also
  Status Clinical Trial Phase
Completed NCT03793985 - Compare the Pharmacokinetics and Safety of CKD-391 With Co-administration of D086 and D337 Phase 1
Recruiting NCT03947866 - Ezetimibe-Rosuvastatin Evaluation Study
Withdrawn NCT04922424 - Mechanisms and Interventions to Address Cardiovascular Risk of Gender-affirming Hormone Therapy in Trans Men Phase 1
Completed NCT04516291 - A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70) Phase 2
Completed NCT04701775 - Effect of Different Probiotic Strains in Hypercholesterolemic Patients N/A
Completed NCT03632668 - Evaluating the Pharmacokinetic Interaction Between AD-2071 and AD-2072 Phase 1
Completed NCT03422666 - Plasma Lipoprotein Response to Glucagon-like Peptide-2 Phase 2/Phase 3
Completed NCT00536796 - Percentage of Secondary Prevention Patients Treated to Their LDL-C Targets N/A
Completed NCT03643705 - A Nurse-led Intervention to Extend the HIV Treatment Cascade for Cardiovascular Disease Prevention N/A
Recruiting NCT04560296 - Community-based E-Health Program for Older Adults Living With Chronic Diseases N/A
Terminated NCT04073134 - The CHORAL Flow Study Phase 4
Recruiting NCT05103254 - Bempedoic Acid Pregnancy Surveillance Program
Not yet recruiting NCT05015348 - Effects of Omega-3 PUFA on Lipids, Inflammatory Factors and Body Composition in Patients With Hyperlipidemia N/A
Active, not recruiting NCT05082350 - Nutritional Intervention With Black Garlic N/A
Not yet recruiting NCT04398771 - To Evaluate Safety and Effectiveness of RovatitanTab.
Not yet recruiting NCT04064281 - The Healthy Cantonese Diet on Cardiometabolic Syndrome N/A
Recruiting NCT06257641 - Impact of the Mediterranean Diet on Patients With Psoriasis N/A
Completed NCT03690778 - The PK Characteristics of the Co-administration of Metformin SR and Rosuvastatin and JLP-1310 in Healthy Male Volunteers. Phase 1
Completed NCT04354987 - Compare the Pharmacokinetics and Safety of CKD-391 Phase 1
Completed NCT03337308 - A Study Evaluating the Safety and Efficacy of Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared to Bempedoic Acid, Ezetimibe, and Placebo in Patients Treated With Maximally Tolerated Statin Therapy Phase 3