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
  Purpose

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.


Condition Intervention Phase
High Blood Arsenic Due to Chronic Arsenic Exposure
Other: Placebo
Dietary Supplement: folic acid
Dietary Supplement: creatine
Dietary Supplement: creatine + folic acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • blood arsenic concentrations [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 600
Study Start Date: September 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo daily
Other: Placebo
daily, 24 weeks
Experimental: Folic Acid 400 ug
400 µg folic acid daily
Dietary Supplement: folic acid
400 ug/d for 12 or 24 weeks
Experimental: Folic Acid 800 ug
800 µg folic acid daily
Dietary Supplement: folic acid
800 µg/d for 12 or 24 weeks
Experimental: Creatine
creatine daily
Dietary Supplement: creatine
3 mg/d for 12 weeks
Experimental: Creatine + Folic Acid
creatine + folic acid daily
Dietary Supplement: creatine + folic acid
3 mg creatine/d + 400 µg folic acid/d for 12 weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01050556

Locations
Bangladesh
Columbia University Arsenic Research Project
Dhaka, Bangladesh
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Mary V Gamble, PhD Columbia University, Department of Environmental Health Sciences
  More Information

No publications provided

Responsible Party: Mary Gamble, Associate Professor of Environmental Health Sciences, Columbia University
ClinicalTrials.gov Identifier: NCT01050556     History of Changes
Other Study ID Numbers: AAAC8618, R01CA133595
Study First Received: January 13, 2010
Last Updated: July 31, 2012
Health Authority: United States: Institutional Review Board
Bangladesh: Bangladesh Medical Research Council

Keywords provided by Columbia University:
arsenic
folate
folic acid
creatine
arsenicosis
nutrition

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014