Ignite Creation Date:
2025-12-25 @ 12:22 AM
Ignite Modification Date:
2026-02-25 @ 8:49 PM
Study NCT ID:
NCT02291458
Status:
UNKNOWN
Last Update Posted:
2014-11-14
First Post:
2014-11-11
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
L-arginine and Brown Adipose Tissue
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018149', 'term': 'Glucose Intolerance'}], 'ancestors': [{'id': 'D006943', 'term': 'Hyperglycemia'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001120', 'term': 'Arginine'}], 'ancestors': [{'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': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 26}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2014-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-11', 'completionDateStruct': {'date': '2015-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2014-11-13', 'studyFirstSubmitDate': '2014-11-11', 'studyFirstSubmitQcDate': '2014-11-13', 'lastUpdatePostDateStruct': {'date': '2014-11-14', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2014-11-14', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Standard uptake value of Brown adipose tissue', 'timeFrame': '6 weeks', 'description': 'Glucose uptake by brown adiopse tissue will be assessed by cold-induced 18F-FDG PET-CT scan'}, {'measure': 'Energy expenditure', 'timeFrame': '6 weeks', 'description': 'Energy expenditure will be determined by means of indirect calorimetrie'}, {'measure': 'Fat mass', 'timeFrame': '6 weeks', 'description': 'Fat mass will be determined by DEXA scan'}], 'secondaryOutcomes': [{'measure': 'Body temperatures', 'timeFrame': '6 weeks', 'description': 'Skin and core body temperatures as well as gradients will be assessed by means of iButtons and ingestion of a telemetric pill, respectively.'}, {'measure': 'Skin perfusion and endothelial-dependent and independent vasodilation', 'timeFrame': '6 weeks', 'description': 'This will be measured by means of Laser Doppler Flowmetry (LDF) and iontophoresis'}, {'measure': 'Skeletal muscle mitochondrial respiration/uncoupling', 'timeFrame': '6 weeks', 'description': 'This will be determined in muscle biopsies by using the Oroboros 2k Oxygraph instrument present in our laboratory .'}, {'measure': 'Brown adipocyte recruitment and inflammation in WAT', 'timeFrame': '6 weeks', 'description': 'This will be measured in subcutaneous WAT biopsies by assessing mRNA expression via real time polymerase-chain reaction (RT-PCR) and protein content by immunohistochemical stainings.'}, {'measure': 'Blood parameters', 'timeFrame': '6 weeks', 'description': 'Venous blood will be drawn by means of a catheter placed in the antecubital vein of the underarm. By using radioimmunoassay, high performance liquid chromotogaphy (HPLC) and enzyme-linked immunosorbent assay (ELISA), blood parameters (i.e. lipids, glucose, inflammatory markers and endothelial activation markers) will be analyzed. In addition, we will perform DNA analyses from blood.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Adipose Tissue, Brown', 'Glucose Intolerance', 'Nitric Oxide']}, 'referencesModule': {'references': [{'pmid': '31701693', 'type': 'DERIVED', 'citation': 'Janssen LGM, Van Dam AD, Hanssen MJW, Kooijman S, Nahon KJ, Reinders H, Jazet IM, Van Marken Lichtenbelt WD, Rensen PCN, Appelman-Dijkstra NM, Boon MR. Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men. Diabetes Metab J. 2020 Apr;44(2):326-335. doi: 10.4093/dmj.2019.0031. Epub 2019 Oct 31.'}, {'pmid': '30377712', 'type': 'DERIVED', 'citation': 'Boon MR, Hanssen MJW, Brans B, Hulsman CJM, Hoeks J, Nahon KJ, Bakker C, van Klinken JB, Havekes B, Schaart G, Jazet IM, Rensen PCN, van Marken Lichtenbelt WD. Effect of L-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study. Diabetologia. 2019 Jan;62(1):112-122. doi: 10.1007/s00125-018-4752-6. Epub 2018 Oct 30.'}, {'pmid': '30070030', 'type': 'DERIVED', 'citation': 'Nahon KJ, Kantae V, den Haan R, Hanssen MJW, Harms AC, van der Stelt M, Hankemeier T, Jazet IM, van Marken Lichtenbelt WD, Rensen PCN, Boon MR. Gene Expression of Endocannabinoid System Components in Skeletal Muscle and Adipose Tissue of South Asians and White Caucasians with Overweight. Obesity (Silver Spring). 2018 Aug;26(8):1332-1337. doi: 10.1002/oby.22245. Epub 2018 Aug 1.'}]}, 'descriptionModule': {'briefSummary': 'The South Asian population is facing an epidemic of type 2 diabetes, of which the underlying cause is still unknown. It is currently hypothesized that an ethnic susceptibility towards a disturbed energy metabolism may underlie this disadvantageous metabolic phenotype. In line with this, the investigators recently discovered that Dutch South Asian subjects have 32% lower resting energy expenditure (REE) and 34% lower energy-combusting brown adipose tissue (BAT) compared to matched white Caucasians. Nitric oxide (NO) was recently shown to be crucial for BAT development and, interestingly, South Asians have diminished NO bioavailability. Thus, the disadvantageous metabolic phenotype in South Asians may be caused by diminished NO bioavailability resulting in lower BAT volume. Therefore, the investigators hypothesize that increasing NO generation in the body by administration of L-arginine, the precursor of NO, will improve their metabolic phenotype by increasing BAT volume, thereby increasing REE and clearance of triglycerides and glucose by BAT. To investigate this, the investigators will perform a randomized placebo-controlled multicenter cross-over study in moderately obese Dutch South Asians and matched white Caucasians. Subjects will receive L-arginine (9 gram/day) or placebo for 6 weeks, followed by a wash-out period of 4 weeks and then again 6 weeks of one of either treatments. At the end of both treatment periods, a cold-induced PET-CT scan will be performed. Furthermore, muscle and fat biopsies will be obtained and thermoregulation will be assessed.', 'detailedDescription': 'Rationale: The South Asian population originally descends from the Indian subcontinent and represents approximately 20% of the total world population. This population is facing an epidemic of type 2 diabetes, of which the underlying cause is still unknown. A high prevalence of a disadvantageous metabolic phenotype, consisting of obesity, insulin resistance and dyslipidemia, may at least in part contribute to this excess risk. It is currently hypothesized that an ethnic susceptibility towards a disturbed energy metabolism may underlie this disadvantageous metabolic phenotype. In line with this, the investigators recently discovered that Dutch South Asian subjects have 32% lower resting energy expenditure (REE) and 34% lower energy-combusting brown adipose tissue (BAT) compared to matched white Caucasians. Nitric oxide (NO) was recently shown to be crucial for BAT development and, interestingly, South Asians have diminished NO bioavailability. Thus, the disadvantageous metabolic phenotype in South Asians may be caused by diminished NO bioavailability resulting in lower BAT volume. Therefore, the investigators hypothesize that increasing NO generation in the body by administration of L-arginine, the precursor of NO, will improve their metabolic phenotype by increasing BAT volume, thereby increasing REE and clearance of triglycerides and glucose by BAT.\n\nObjectives: The primary objectives are: 1) to determine the effect of L-arginine on glucose uptake by brown adipose tissue and to assess whether the effect differs between South Asian and white Caucasian subjects; 2) to determine the effect of L-arginine on whole body energy expenditure and to assess whether the effect differs between South Asian and white Caucasian subjects; 3) to determine the effect of L-arginine on fat mass and to assess whether the effect differs between South Asian and white Caucasian subjects.\n\nStudy design: A randomized placebo-controlled multicenter cross-over study will be performed in moderately obese Dutch South Asians and matched white Caucasians. Subjects will receive L-arginine (9 gram/day) or placebo for 6 weeks, followed by a wash-out period of 4 weeks and then again 6 weeks of one of either treatments. At the end of both treatment periods, a cold-induced PET-CT scan will be performed. Furthermore, muscle and fat biopsies will be obtained, thermoregulation will be assessed, an oral glucose tolerance will be performed and the investigators will assess NO-dependent and independent vasodilation by means of iontophoresis.\n\nStudy population: Mildly obese (BMI 25-30 kg/m2) pre-diabetic male volunteers of South Asian and white Caucasian descent aged between 35-50 years.\n\nIntervention: The intervention will consist of administration of 9 grams of L-arginine per day in three gifts (3dd 3 gram).'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '50 Years', 'minimumAge': '35 Months', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Caucasian or South Asian ethnicity\n* Age: 35-50 years\n* Gender: male\n* BMI: 25-30 kg/m2\n* Plasma glucose levels 2 h after OGTT between 7.8 and 11 mM (e.g. impaired glucose tolerance) or Fasting plasma glucose levels \\> 5.5 mM\n* Good general health\n\nExclusion Criteria:\n\n* Type 2 diabetes (determined on basis of oral glucose tolerance test (OGTT))\n* BMI \\> 30 kg/m2\n* Plasma glucose levels 2 h after OGTT \\< 7.8 mM\n* Plasma L-arginine levels \\< 41 or \\> 114 uM\n* Use of beta-blockers (these inhibit BAT activity) \\< 1 month before start of study or during study\n* Systolic blood pressure \\< 90 mmHg\n* Haematocrit \\< 0.41 or \\> 0.51 l/l\n* Haemoglobin \\< 8.5 or \\> 11.0\n* Creatinine (enzymatic method) \\< 45 or \\> 100 μmol/L\n* ASAT \\> 45 U/L\n* ALAT \\> 50 U/L\n* Alkaline phosphatase \\> 125 U/L\n* Gamma GT \\> 45 U/L\n* Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study\n* Abuse of drugs and/or alcohol\n* Hyperthyroidism or hypothyroidism\n* Participation in earlier research or medical examinations that included PET-CT scanning\n* Psychologically unstable subjects (as judged by the treating medical specialist)\n* Subjects with mental retardation (as judged by the treating medical specialist)\n* Subjects with severe behaviour disorders (as judged by the treating medical specialist)'}, 'identificationModule': {'nctId': 'NCT02291458', 'acronym': 'ArgMB', 'briefTitle': 'L-arginine and Brown Adipose Tissue', 'organization': {'class': 'OTHER', 'fullName': 'Maastricht University Medical Center'}, 'officialTitle': 'The Effect of L-arginine on Brown Adipose Tissue Metabolism in South Asian and White Caucasian Subjects', 'orgStudyIdInfo': {'id': 'NL2014-001733-86'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'L-arginine', 'description': 'Subjects will receive 9 gram of L-arginine per day in three gifts (3dd 3 gram) during 6 weeks.', 'interventionNames': ['Drug: L-arginine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Subjects will receive 9 gram of placebo per day in three gifts (3 dd 3 gram) during 6 weeks.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'L-arginine', 'type': 'DRUG', 'otherNames': ['Argimax'], 'description': '9 gram L-arginine / day for 6 weeks', 'armGroupLabels': ['L-arginine']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '9 gram placebo / day for 6 weeks', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '6229 ER', 'city': 'Maastricht', 'state': 'Limburg', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Mariette Boon, PhD', 'role': 'CONTACT', 'email': 'm.boon@maastrichtuniversity.nl', 'phone': '+31648126425'}, {'name': 'Wouter van Marken Lichtenbelt, PhD', 'role': 'CONTACT', 'email': 'markenlichtenbelt@maastrichtuniversity.nl', 'phone': 'Tel: +31 43 388 1629'}], 'facility': 'Maastricht University Medical Center +', 'geoPoint': {'lat': 50.84833, 'lon': 5.68889}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Maastricht University Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'Leiden University Medical Center', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}