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:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006949', 'term': 'Hyperlipidemias'}], 'ancestors': [{'id': 'D050171', 'term': 'Dyslipidemias'}, {'id': 'D052439', 'term': 'Lipid Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C494910', 'term': 'teduglutide'}, {'id': 'D000077330', 'term': 'Saline Solution'}, {'id': 'D019323', 'term': 'omega-N-Methylarginine'}], 'ancestors': [{'id': 'D000077324', 'term': 'Crystalloid Solutions'}, {'id': 'D007552', 'term': 'Isotonic Solutions'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D001120', 'term': 'Arginine'}, {'id': 'D024361', 'term': 'Amino Acids, Basic'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D000599', 'term': 'Amino Acids, Diamino'}, {'id': 'D000601', 'term': 'Amino Acids, Essential'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT'], 'maskingDescription': 'Single-blinded for participants'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Each participant receives 3 randomized treatments.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-09-27', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-03', 'completionDateStruct': {'date': '2019-03-20', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-03-26', 'studyFirstSubmitDate': '2018-05-11', 'studyFirstSubmitQcDate': '2018-05-11', 'lastUpdatePostDateStruct': {'date': '2020-03-27', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-05-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-03-20', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Plasma Lipid Levels', 'timeFrame': '10.5 hours', 'description': 'Lipid levels in plasma and lipoprotein fractions are measured following treatments'}], 'secondaryOutcomes': [{'measure': 'Blood Flow', 'timeFrame': '3 hours', 'description': 'Mesenteric blood flow rates are measured with ultrasound following treatments'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Hyperlipidemias']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nStudy 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.\n\nStudy 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.\n\nStudy C (Placebo + L-NMMA): The design is identical to study A, except that, instead of Teduglutide, a placebo will be injected subcutaneously.\n\nMesenteric 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Men and women, aged 18 to 60 years\n* Body mass index 20 kg/m2 to 30 kg/m2\n* Hemoglobin above 130g/L.\n* Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test\n\nExclusion Criteria:\n\n* Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.\n* 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\n* History of diabetes or oral glucose tolerance indicative of diabetes or impaired glucose tolerance.\n* 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.\n* Any laboratory values: aspartate transaminase \\> 2x upper limit of normal; alanine aminotransferase \\> 2x upper limit of normal; thyroid-stimulating hormone \\> 6 miliunit/l\n* Current addiction to alcohol or substances of abuse as determined by the investigator.\n* Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation\n* Taking any prescription or non-prescription medications at the time of the study\n* Having donated blood three months prior to and three months post study procedures\n* 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."}, 'identificationModule': {'nctId': 'NCT03534661', 'acronym': 'LNMMA', 'briefTitle': 'L-NMMA on GLP-2 Mediated Intestinal Lipoprotein Release', 'organization': {'class': 'OTHER', 'fullName': 'University Health Network, Toronto'}, 'officialTitle': 'Role of a Nitric Oxide Synthase Inhibitor on GLP-2 Mediated Intestinal Lipoprotein Release', 'orgStudyIdInfo': {'id': 'L-NMMA 13-6415'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Teduglutide + Normal Saline', 'description': 'Teguglutide + (L-NMMA control)', 'interventionNames': ['Drug: Teduglutide + Normal Saline']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Teduglutide + L-NMMA', 'description': 'Tedulgutide + L-NMMA', 'interventionNames': ['Drug: Teduglutide + L-NMMA']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo + L-NMMA', 'description': '(Teduglutide control) + L-NMMA', 'interventionNames': ['Drug: Placebo + L-NMMA']}], 'interventions': [{'name': 'Teduglutide + Normal Saline', 'type': 'DRUG', 'otherNames': ['L-NMMA control'], 'description': 'Teduglutide 0.05 mg/kg subcutaneous injection; Normal Saline intravenous infusion', 'armGroupLabels': ['Teduglutide + Normal Saline']}, {'name': 'Teduglutide + L-NMMA', 'type': 'DRUG', 'otherNames': ['active treatments'], 'description': 'Teduglutide 0.05 mg/kg subcutaneous injection; L-NMMA 10 mg/kg intravenous infusion', 'armGroupLabels': ['Teduglutide + L-NMMA']}, {'name': 'Placebo + L-NMMA', 'type': 'DRUG', 'otherNames': ['Teduglutide control'], 'description': 'Placebo subcutaneous injection; L-NMMA 10 mg/kg intravenous infusion', 'armGroupLabels': ['Placebo + L-NMMA']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M5G 1L7', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Tornto General Hospital, UHN', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Health Network, Toronto', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}