Ignite Creation Date:
2025-12-24 @ 11:29 PM
Ignite Modification Date:
2025-12-29 @ 2:30 PM
Study NCT ID:
NCT01050556
Status:
COMPLETED
Last Update Posted:
2012-08-01
First Post:
2010-01-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D005492', 'term': 'Folic Acid'}, {'id': 'D003401', 'term': 'Creatine'}], 'ancestors': [{'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 600}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2012-07', 'completionDateStruct': {'date': '2011-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2012-07-31', 'studyFirstSubmitDate': '2010-01-13', 'studyFirstSubmitQcDate': '2010-01-13', 'lastUpdatePostDateStruct': {'date': '2012-08-01', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2010-01-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'blood arsenic concentrations', 'timeFrame': '24 weeks'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['arsenic', 'folate', 'folic acid', 'creatine', 'arsenicosis', 'nutrition'], 'conditions': ['High Blood Arsenic Due to Chronic Arsenic Exposure']}, 'referencesModule': {'references': [{'pmid': '40668877', 'type': 'DERIVED', 'citation': 'Li W, Wu H, Goldsmith J, Glabonjat RA, Ilievski V, Balac O, Slavkovich V, Pinto-Pacheco B, Lin X, Parvez F, Jackson GL, Siddique AB, Uddin MN, Islam T, Martinez-Morata I, Navas-Acien A, Niedzwiecki MM, Kioumourtzoglou MA, Pierce BL, Graziano JH, Bottiglieri T, Walker DI, Gamble MV. Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial. Environ Sci Technol. 2025 Jul 29;59(29):14905-14916. doi: 10.1021/acs.est.5c01597. Epub 2025 Jul 16.'}, {'pmid': '38092151', 'type': 'DERIVED', 'citation': 'Martinez-Morata I, Wu H, Galvez-Fernandez M, Ilievski V, Bottiglieri T, Niedzwiecki MM, Goldsmith J, Jones DP, Kioumourtzoglou MA, Pierce B, Walker DI, Gamble MV. Metabolomic Effects of Folic Acid Supplementation in Adults: Evidence from the FACT Trial. J Nutr. 2024 Feb;154(2):670-679. doi: 10.1016/j.tjnut.2023.12.010. Epub 2023 Dec 12.'}, {'pmid': '36976258', 'type': 'DERIVED', 'citation': 'Abuawad AK, Bozack AK, Navas-Acien A, Goldsmith J, Liu X, Hall MN, Ilievski V, Lomax-Luu AM, Parvez F, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population. Environ Health Perspect. 2023 Mar;131(3):37015. doi: 10.1289/EHP11270. Epub 2023 Mar 28.'}, {'pmid': '34661903', 'type': 'DERIVED', 'citation': 'Bae S, Kamynina E, Guetterman HM, Farinola AF, Caudill MA, Berry RJ, Cassano PA, Stover PJ. Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD012649. doi: 10.1002/14651858.CD012649.pub2.'}, {'pmid': '32918135', 'type': 'DERIVED', 'citation': 'Bozack AK, Howe CG, Hall MN, Liu X, Slavkovich V, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults. Eur J Nutr. 2021 Jun;60(4):1921-1934. doi: 10.1007/s00394-020-02377-z. Epub 2020 Sep 11.'}, {'pmid': '30590411', 'type': 'DERIVED', 'citation': 'Bozack AK, Hall MN, Liu X, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh. Am J Clin Nutr. 2019 Feb 1;109(2):380-391. doi: 10.1093/ajcn/nqy148.'}, {'pmid': '27052531', 'type': 'DERIVED', 'citation': 'Hall MN, Howe CG, Liu X, Caudill MA, Malysheva O, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults. J Nutr. 2016 May;146(5):1062-7. doi: 10.3945/jn.115.227132. Epub 2016 Apr 6.'}, {'pmid': '26311810', 'type': 'DERIVED', 'citation': 'Peters BA, Hall MN, Liu X, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Ilievski V, Graziano JH, Gamble MV. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. J Nutr. 2015 Oct;145(10):2245-52. doi: 10.3945/jn.115.216739. Epub 2015 Aug 26.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine whether folic acid, alone or together with creatine supplementation, can lower blood arsenic concentrations and improve the ability to detoxify arsenic.', 'detailedDescription': 'Approximately 140 million people in over 70 countries are chronically exposed to arsenic (As)-contaminated drinking water at concentrations far exceeding the World Health Organization standard of 10 µg/L. As is a carcinogen known to cause cancers of the skin, bladder, and lung, as well as ischemic heart disease and neurologic impairments. Methylation of ingested inorganic arsenic (InAs) to methylarsonic-(MMA) and dimethylarsinic acids (DMA) relies on folate-dependent one carbon metabolism, utilizing S-adenosylmethionine (SAM) as the methyl donor, and facilitates urinary As elimination. The results from our Nutritional Influences on Arsenic Toxicity (NIAT) study indicate that folate deficiency and hyperhomocysteinemia (HHcys) are associated with a reduced capacity to methylate arsenic and are risk factors for arsenic-induced skin lesions. Furthermore, folic acid (FA) supplementation does indeed facilitate As elimination and significantly lowers blood As concentrations in individuals who are folate deficient. We have also determined that blood As is a good biomarker of As exposure and is directly associated with the risk for As-induced skin lesions. Collectively, the implication of these findings is that FA has enormous therapeutic potential for ameliorating the long-term health consequences of arsenic exposure for the many populations at risk. However, several fundamental questions remain and will be addressed in this study. This trial is designed to determine 1) whether FA supplementation lowers blood As concentrations in the general Bangladeshi population, 2) at what time point a nadir in blood As is achieved, and 3) whether creatine supplementation, alone or in addition to 400 µg/d FA, will spare methyl groups, resulting in lower blood As, lower homocysteine (Hcys) concentrations, and increased methylation of As. The creatine arms are based on multiple studies that show that urinary creatinine concentrations are a very strong predictor of As methylation. The final step in creatine biosynthesis is the methylation of guanidinoacetate to creatine; this process consumes 50-75% of all SAM-derived methyl groups and is also responsible for 50-75% of all Hcys biosynthesis. Thus, this trial will test the hypothesis that creatine supplementation, which shuts down endogenous creatine biosynthesis, will spare methyl groups, lower Hcys, and increase As methylation.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '20 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Currently exposed to arsenic via contaminated drinking water\n* Well water arsenic concentration \\> 10 ug/L\n* Between the ages of 20 and 65\n\nExclusion Criteria:\n\n* Women who are currently pregnant or plan to become pregnant within the next 6 months\n* Currently taking nutritional supplements\n* Known renal disease\n* Participation in any other clinical trial'}, 'identificationModule': {'nctId': 'NCT01050556', 'acronym': 'FACTA', 'briefTitle': 'Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic', 'organization': {'class': 'OTHER', 'fullName': 'Columbia University'}, 'officialTitle': 'Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic', 'orgStudyIdInfo': {'id': 'AAAC8618'}, 'secondaryIdInfos': [{'id': 'R01CA133595', 'link': 'https://reporter.nih.gov/quickSearch/R01CA133595', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo daily', 'interventionNames': ['Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Folic Acid 400 ug', 'description': '400 µg folic acid daily', 'interventionNames': ['Dietary Supplement: folic acid']}, {'type': 'EXPERIMENTAL', 'label': 'Folic Acid 800 ug', 'description': '800 µg folic acid daily', 'interventionNames': ['Dietary Supplement: folic acid']}, {'type': 'EXPERIMENTAL', 'label': 'Creatine', 'description': 'creatine daily', 'interventionNames': ['Dietary Supplement: creatine']}, {'type': 'EXPERIMENTAL', 'label': 'Creatine + Folic Acid', 'description': 'creatine + folic acid daily', 'interventionNames': ['Dietary Supplement: creatine + folic acid']}], 'interventions': [{'name': 'Placebo', 'type': 'OTHER', 'description': 'daily, 24 weeks', 'armGroupLabels': ['Placebo']}, {'name': 'folic acid', 'type': 'DIETARY_SUPPLEMENT', 'description': '400 ug/d for 12 or 24 weeks', 'armGroupLabels': ['Folic Acid 400 ug']}, {'name': 'folic acid', 'type': 'DIETARY_SUPPLEMENT', 'description': '800 µg/d for 12 or 24 weeks', 'armGroupLabels': ['Folic Acid 800 ug']}, {'name': 'creatine', 'type': 'DIETARY_SUPPLEMENT', 'description': '3 mg/d for 12 weeks', 'armGroupLabels': ['Creatine']}, {'name': 'creatine + folic acid', 'type': 'DIETARY_SUPPLEMENT', 'description': '3 mg creatine/d + 400 µg folic acid/d for 12 weeks', 'armGroupLabels': ['Creatine + Folic Acid']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Dhaka', 'country': 'Bangladesh', 'facility': 'Columbia University Arsenic Research Project', 'geoPoint': {'lat': 23.7104, 'lon': 90.40744}}], 'overallOfficials': [{'name': 'Mary V Gamble, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Columbia University, Department of Environmental Health Sciences'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Columbia University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Environmental Health Sciences', 'investigatorFullName': 'Mary Gamble', 'investigatorAffiliation': 'Columbia University'}}}}