Ignite Creation Date:
2025-12-25 @ 1:37 AM
Ignite Modification Date:
2025-12-26 @ 12:22 AM
Study NCT ID:
NCT04142294
Status:
COMPLETED
Last Update Posted:
2022-02-07
First Post:
2018-10-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety of Graded-Dose of Histidine in Humans
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D006639', 'term': 'Histidine'}], 'ancestors': [{'id': 'D000598', 'term': 'Amino Acids, Cyclic'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D000601', 'term': 'Amino Acids, Essential'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Histidine supplementation trial, non-randomized, sequential delivery of graded doses of the amino acid histidine. All participants serve as their own controls. Following baseline measurements, subjects ingest encapsulated high quality histidine for four continuous weeks at graded doses of 4, 8 and 12 g/day. A forth dose at 16 g/day is assessed if no adverse outcomes are observed for the three graded doses. Histidine doses are suggested based on experience with other amino acids (relative difference of average intake and metabolic limits). Each dose is followed by a 3-week minimum recovery period. During the recovery period, subjects will continue to be monitored (vitals and weight) but no supplementation is consumed. At the conclusion of each washout period, before the start of the next dose, subjects provide a blood sample, vitals (blood pressure and heart rate), weight, 4-day diet record, sleep log, hunger and satiety VAS, mood VAS, and physical activity monitoring.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-09-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-01', 'completionDateStruct': {'date': '2019-08-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-01-24', 'studyFirstSubmitDate': '2018-10-30', 'studyFirstSubmitQcDate': '2019-10-25', 'lastUpdatePostDateStruct': {'date': '2022-02-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-10-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-08-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in concentration of zinc in mg/ml', 'timeFrame': 'at week 0 and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through blood markers of zinc'}, {'measure': 'Change in concentration of liver enzymes (ALT, ALP, and AST) in Units per Liter', 'timeFrame': 'at weeks 0 (washout), 2 and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through circulating liver enzymes'}, {'measure': 'Change in body weight in kilograms', 'timeFrame': 'at weeks 0 (washout), 2 and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through changes in weight'}, {'measure': 'Change in concentration of total protein and albumin in g/dl', 'timeFrame': 'at weeks 2 and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through circulating total protein and albumin'}, {'measure': 'Change in concentration of blood urea nitrogen, Creatinine, bilirubin and glucose each in mg/gL', 'timeFrame': 'at weeks 0 (washout), 2 and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through circulating blood urea nitrogen, Creatinine, bilirubin and glucose'}, {'measure': 'Change in concentration of C-reactive protein mg/L', 'timeFrame': 'at weeks 0 (washout), 2 and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through circulating CRP'}, {'measure': 'HgbA1c in %', 'timeFrame': 'at week 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through circulating HgbA1c'}, {'measure': 'Change in heart rate in beats per minute', 'timeFrame': 'weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through heart rate'}, {'measure': 'Change in systolic and diastolic blood pressures in mmHG', 'timeFrame': 'weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose', 'description': 'The safety of histidine supplementation at each dose is monitored through blood pressure'}], 'secondaryOutcomes': [{'measure': 'Change in hours of sleep', 'timeFrame': 'week 0 to 4 of each dose', 'description': 'The effects of histidine will be assessed with changes in sleep pattern as determined using a subjective measurement tool'}, {'measure': 'Change in dietary intake of energy, macronutrients, and amino acids measured in kcals and g/day with 4 day food record', 'timeFrame': 'week 0 to 4 of each dose', 'description': 'The effects of histidine will be assessed with changes dietary intake as determined with 4 day food records'}, {'measure': 'Change in physical activity measured in steps per day', 'timeFrame': 'week 0 to 4 of each dose', 'description': 'The effects of histidine will be assessed with changes in physical activity patterns using an Actigraph'}, {'measure': 'Change in subjective mood measured in arbitrary units', 'timeFrame': 'week 0 to 4 of each dose', 'description': 'The effects of histidine will be assessed with changes in mood as determined using a subjective visual analog scale. 100 mm line is anchored by two opposing statements. The higher number the greater the mood.'}, {'measure': 'Change in subjective desire to eat measured in arbitrary units', 'timeFrame': 'week 0 to 4 of each dose', 'description': 'The effects of histidine will be assessed with changes in desire to eat will be determined using a visual analog scale. 100 mm line is anchored by two opposing statements. The greater the number the stronger the desire.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Healthy']}, 'referencesModule': {'references': [{'pmid': '32766885', 'type': 'DERIVED', 'citation': 'Gheller ME, Vermeylen F, Handzlik MK, Gheller BJ, Bender E, Metallo C, Aydemir TB, Smriga M, Thalacker-Mercer AE. Tolerance to graded dosages of histidine supplementation in healthy human adults. Am J Clin Nutr. 2020 Nov 11;112(5):1358-1367. doi: 10.1093/ajcn/nqaa210.'}]}, 'descriptionModule': {'briefSummary': 'Histidine is an essential amino acid with health benefits that include anti-inflammatory, anti-oxidant, glucoregulatory, and weight management. The current expert opinion for histidine intake is 8 and 12 mg/(kg body weight per day), an estimate that was extrapolated from the infant requirement for histidine. Further, the clinical safety of histidine supplementation above the average dietary intake has not been determined.The overarching objectives are to 1) measure the safety of histidine supplementation and 2) measure the potential benefits of histidine at doses above the average intake and current recommendation in a healthy adult population.', 'detailedDescription': 'Histidine is an essential amino acid with health benefits that include anti-inflammatory, anti-oxidant, glucoregulatory, and weight management. Because of the extended period of time (\\>35 days) that is required to deplete body histidine pools in adults, it has not been possible to fully determine histidine requirements. The current expert opinion for histidine intake is 8 and 12 mg/(kg body weight per day), an estimate that was extrapolated from the infant requirement for histidine. The average intake of histidine from a normal adult diet in the U.S., Europe, and Japan was reported between 2.12 and 2.40 g/day with the 99th percentile intake in men at 50-70 years of age consuming 5.20 g/day. The clinical safety of histidine supplementation above the average dietary intake has not been determined. Therefore, this study will utilize graded doses of histidine that are at are moderately above the average intake to identify safety and benefits of histidine in a healthy human population. Further, the clinical safety of histidine supplementation above the average dietary intake has not been determined.The overarching objectives are to 1) measure the safety of histidine supplementation and 2) measure the potential benefits of histidine at doses above the average intake and current recommendation in a healthy adult population. Following the completion and review of a health history questionnaire, vitals, and a biochemical panel, participants will be deemed healthy by a nurse practitioner and able to participate. After baseline measures are obtained, supplements (encapsulated histidine) will be provided at three graded doses (4 g/day, 8 g/day and 12 g/day) a forth dose (16 g/day) will be consumed if no adverse effects are observed at the three graded doses. Each dose will be for 28 days followed by a three week recovery period. At baseline, weeks 2 and 4 of supplement, and recovery a basic biochemical panel, anthropometric, urinary and serum zinc, will be conducted. Additionally, body composition will be conducted at baseline and week 4 of each dose. Changes in dietary intake and physical activity will be measured with 4-day food records and Actigraph activity monitors, respectively. Changes in sleep patterns will be measured with the Pittsburgh sleep questionnaire.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '50 Years', 'minimumAge': '21 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n• healthy young males and females aged 21-50 y.\n\nExclusion Criteria:\n\n* A body-mass index (BMI) \\<19.9 kg/m2 or \\> 29.9 kg/m2\n* taking/on immunosuppressive medications or prescription anti-coagulation therapy\n* pregnancy\n* breastfeeding\n* musculoskeletal disorder\n* diabetes\n* alcoholism (\\>11 drinks per week for women, \\>14 drinks per week for men) or other drug addiction\n* acute illness\n* inability to travel to Cornell University campus\n* A blood pressure at or above 140/90\n* For individuals desiring to participate in the optional biopsy, a history of a negative or allergic reaction to local anesthetic is an exclusion criteria'}, 'identificationModule': {'nctId': 'NCT04142294', 'briefTitle': 'Safety of Graded-Dose of Histidine in Humans', 'organization': {'class': 'OTHER', 'fullName': 'Cornell University'}, 'officialTitle': 'Safety of Graded-Dose of Histidine as Determined by Circulating Analytes, Sleep Records, Physical Activity, Anthropometric Measurements, and Mood', 'orgStudyIdInfo': {'id': '83676/A001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '4 g / day histidine', 'description': 'subjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day.', 'interventionNames': ['Dietary Supplement: Histidine']}, {'type': 'EXPERIMENTAL', 'label': '8 g / day histidine', 'description': 'subjects ingest encapsulated high quality histidine for four continuous weeks at 8 g/day', 'interventionNames': ['Dietary Supplement: Histidine']}, {'type': 'EXPERIMENTAL', 'label': '12 g /day histidine', 'description': 'subjects ingest encapsulated high quality histidine for four continuous weeks at 12 g/day', 'interventionNames': ['Dietary Supplement: Histidine']}, {'type': 'EXPERIMENTAL', 'label': '16 g /day histidine', 'description': 'subjects ingest encapsulated high quality histidine for four continuous weeks at 16 g/day. The 16 g /day dose will be administered if no adverse effects are observed for doses 4-12 g/day', 'interventionNames': ['Dietary Supplement: Histidine']}], 'interventions': [{'name': 'Histidine', 'type': 'DIETARY_SUPPLEMENT', 'description': 'ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks', 'armGroupLabels': ['12 g /day histidine', '16 g /day histidine', '4 g / day histidine', '8 g / day histidine']}]}, 'contactsLocationsModule': {'locations': [{'zip': '14853', 'city': 'Ithaca', 'state': 'New York', 'country': 'United States', 'facility': 'Human Metabolic Research Unit', 'geoPoint': {'lat': 42.44063, 'lon': -76.49661}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Cornell University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}