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

July 31, 2012 updated by: Mary Gamble, Columbia University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

600

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bangladesh
      • Dhaka, Bangladesh
        • Columbia University Arsenic Research Project

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Dietary supplement: folic acid
800 µg/d for 12 or 24 weeks
Experimental: Folic Acid 800 ug
800 µg folic acid daily
Dietary supplement: folic acid
400 ug/d for 12 or 24 weeks
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
blood arsenic concentrations
Time Frame: 24 weeks
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Mary V Gamble, PhD, Columbia University, Department of Environmental Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

January 13, 2010

First Submitted That Met QC Criteria

January 13, 2010

First Posted (Estimate)

January 15, 2010

Study Record Updates

Last Update Posted (Estimate)

August 1, 2012

Last Update Submitted That Met QC Criteria

July 31, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAC8618
  • R01CA133595 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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