Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic (FACTA)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mary Gamble, Columbia University
ClinicalTrials.gov Identifier:
NCT01050556
First received: January 13, 2010
Last updated: July 31, 2012
Last verified: July 2012

January 13, 2010
July 31, 2012
September 2010
June 2011   (final data collection date for primary outcome measure)
blood arsenic concentrations [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01050556 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic
Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
High Blood Arsenic Due to Chronic Arsenic Exposure
  • Other: Placebo
    daily, 24 weeks
  • Dietary Supplement: folic acid
    400 ug/d for 12 or 24 weeks
  • Dietary Supplement: folic acid
    800 µg/d for 12 or 24 weeks
  • Dietary Supplement: creatine
    3 mg/d for 12 weeks
  • Dietary Supplement: creatine + folic acid
    3 mg creatine/d + 400 µg folic acid/d for 12 weeks
  • Placebo Comparator: Placebo
    Placebo daily
    Intervention: Other: Placebo
  • Experimental: Folic Acid 400 ug
    400 µg folic acid daily
    Intervention: Dietary Supplement: folic acid
  • Experimental: Folic Acid 800 ug
    800 µg folic acid daily
    Intervention: Dietary Supplement: folic acid
  • Experimental: Creatine
    creatine daily
    Intervention: Dietary Supplement: creatine
  • Experimental: Creatine + Folic Acid
    creatine + folic acid daily
    Intervention: Dietary Supplement: creatine + folic acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
600
June 2011
June 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Currently exposed to arsenic via contaminated drinking water
  • Well water arsenic concentration > 10 ug/L
  • Between the ages of 20 and 65

Exclusion Criteria:

  • Women who are currently pregnant or plan to become pregnant within the next 6 months
  • Currently taking nutritional supplements
  • Known renal disease
  • Participation in any other clinical trial
Both
20 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Bangladesh
 
NCT01050556
AAAC8618, R01CA133595
Yes
Mary Gamble, Columbia University
Columbia University
National Cancer Institute (NCI)
Principal Investigator: Mary V Gamble, PhD Columbia University, Department of Environmental Health Sciences
Columbia University
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP