Mitigation Efforts in Arsenic Exposure With Folic Acid Supplementation

Study Overview
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Brief Summary
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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.

Detailed Description
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Folic acid supplementation effects urinary arsenic excretion. In this project investigators propose to investigate if oral folic acid dietary supplementation can increase urinary arsenic metabolite excretion

Official Title
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Mitigation Efforts in Arsenic Exposure With Folic Acid Supplementation: Reducing Toxicity and Exploring the Impact on Lung Health

Conditions
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Arsenic and/or Arsenic Compound Adverse Reaction

Intervention / Treatment
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* Dietary Supplement: Folic Acid
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥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 Exclusion Criteria: Pregnancy Ongoing folic acid nutritional supplementation Methotrexate use Megaloblastic anemia Alcoholic liver disease Malabsorptive syndromes - celiac disease, inflammatory bowel disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo daily 12 weeks | Other: Placebo<br>* Placebo group to assess arsenic metabolite excretion<br>|
| Experimental: Folic Acid<br>Folic acid 800 ug/day 12 weeks | Dietary Supplement: Folic Acid<br>* Folic acid supplementation to assess for increased arsenic metabolite excretion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Symptom Questionnaire | The Respiratory Symptom Questionnaire (RSQ) is an instrument that assesses the frequency of respiratory symptoms and their impact on patients' activity over the previous four weeks, without requiring a specific diagnostic label of asthma or chronic obstructive pulmonary disease (COPD). The four questions assess the frequency of respiratory symptoms (shortness of breath, wheezing, coughing, and/or chest tightness) during the day and, in response to these respiratory symptoms, frequency of rescue inhaler use, activity limitations and frequency of night-time awakening. We will administer the RSQ to participants at the baseline screening. Maximum value 16, minimum value 4, higher scores represent increased symptom burden. | 12 weeks | 
| Pooled Cohort Probability Score | The pooled cohort probability score has been used to detect subclinical airway obstruction. Age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years will be obtained and the score will be computed at baseline. | 12 weeks |