Mitigation Efforts in Arsenic Exposure With Folic Acid Supplementation

NCT05656664 | Enrolling By Invitation DMC

• 1 other identifier: 300010144
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effects on folic acid supplementation in a population living in an environment with chronic arsenic exposure in Birmingham, Alabama.

Conditions

Arsenic and/or Arsenic Compound Adverse Reaction

Outcome Measures

Primary Outcomes (1)

• Measurement of urine and blood arsenic metabolites

  Inorganic As (InAs) within humans undergoes a stepwise biotransformation reaction in which it is methylated to monomethyl-arsonic acid (MMAsIII), and dimethylarsinic acid (DMAsV) facilitating urinary excretion. This occurs via arsenic methyltransferase (AS3MT) using a methyl donor S-adenosylmethionine (SAM). In this pathway the one-carbon unit carried by 5-methyl-tetrahydrofolate (5-MTHF) is transferred to homocysteine to form methionine, which is activated to SAM. Complete methylation to DMAsV is critical as higher proportion of MMAs(III+V) are associated with skin lesions, peripheral vascular disease, atherosclerosis, and cancers. We will measure levels of InAs, total DMA and MMA in the urine and blood of the study subjects at baseline and 12 weeks. Outcomes will be reported in percentage (%) of InAs, DMA and MMA in blood and urine.

  12 weeks

Secondary Outcomes (2)

• Respiratory Symptom Questionnaire

  12 weeks

• Pooled Cohort Probability Score

  12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo daily 12 weeks

Other: Placebo

Folic Acid

EXPERIMENTAL

Folic acid 800 ug/day 12 weeks

Dietary Supplement: Folic Acid

Interventions

Folic Acid DIETARY_SUPPLEMENT

Folic acid supplementation to assess for increased arsenic metabolite excretion

Folic Acid

Placebo OTHER

Placebo group to assess arsenic metabolite excretion

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age
• Resident of the superfund site
• Clinically stable with no significant changes in general health status in the past 4 weeks prior to screening as assessed by the investigator
• Provide written informed consent

You may not qualify if:

• Pregnancy
• Ongoing folic acid nutritional supplementation
• Methotrexate use
• Megaloblastic anemia
• Alcoholic liver disease
• Malabsorptive syndromes - celiac disease, inflammatory bowel disease

Sponsors & Collaborators

• P42ES027723: collaborator
• University of Alabama at Birmingham: lead
• National Institute of Environmental Health Sciences (NIEHS): collaborator

Study Sites (1)

UAB Lung Health Center

Birmingham, Alabama, 35205, United States

Location

Related Publications (1)

• 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: 30590411 RESULT

MeSH Terms

Interventions

Folic Acid

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kevin G Dsouza, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study randomization will be performed by using a randomization scheme provided by the Investigational Drug Service (IDS). The randomization scheme will be held by IDS and concealed to investigators until the completion of the study.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Study procedures will consist of recruitment of 100 subjects, 50 each in the treatment (Folic Acid, 800 mcg) and placebo groups respectively. Folic Acid 800 mcg or placebo pill bottles will be provided to the participants with instructions to take one pill orally daily. Both the investigators and subjects will be blinded. Compliance will be measured via pill count.

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: December 19, 2022
• Study Start: September 14, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)