A Preliminary Study of Choline and Betaine Supplementation Among Adults Exposed to Arsenic in Bangladesh

Study Overview
=================
Brief Summary
-----------------
Roughly 140 million people worldwide are chronically exposed to As-contaminated drinking water at concentrations exceeding the World Health Organization (WHO) standard of 10 µg/L. Arsenic is a class I carcinogen known to cause several types of cancer and ischemic heart disease. Metabolism of inorganic As (InAs), which facilitates urinary As excretion, relies on one-carbon metabolism and involves two methylation steps; both utilize S-adenosylmethionine (SAM) as the methyl donor. SAM biosynthesis relies on B vitamins including folate and B12 for the recruitment and transfer of methyl groups, but other nutrients, including choline and betaine, also contribute to the methyl pool. Our recent findings from a cross-sectional study of Bangladeshi adults exposed to a wide range of As concentrations in drinking water show that plasma choline and betaine concentrations are positively associated with As methylation. These findings suggest that choline and/or betaine may play an important role in As methylation and elimination and that simple interventions may have therapeutic potential for the many populations at risk for As-induced health effects. The investigators aim to recruit and follow 60 participants for this pilot study which will allow us to 1) assess the acceptance of choline and betaine supplements, 2) monitor participants for any potential side effects, 3) identify any difficulties that might be encountered in daily follow-up, and 4) generate preliminary data regarding the effects of choline and/or betaine supplementation on arsenic methylation.

Official Title
-----------------
A Pilot Study of Choline and Betaine Supplementation in Arsenic-exposed Individuals in Bangladesh

Conditions
-----------------
Arsenic Metabolites Measured in Urine

Intervention / Treatment
-----------------
* Other: Placebo
* Drug: Choline bitartrate
* Drug: Betaine
* Drug: Choline bitartrate + Betaine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 20-65 Absence of all exclusion criteria Exclusion Criteria: women who are currently pregnant at the time of recruitment and/or plan to become pregnant within 2 months individuals taking nutritional supplements at the time of recruitment individuals who have taken nutritional supplements within the last 3 months participants enrolled in any other clinical trial women who are currently breastfeeding individuals known to have coronary heart disease, cerebrovascular disease, hypertension, renal disease, chronic obstructive pulmonary disease, asthma, cancer, or liver disease participants with protein or glucose in their urine sample (dipstick test) individuals whose drinking water history is complete for < 3 months

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo tablets | Other: Placebo<br> <br> |
| Experimental: Choline bitartrate<br>Choline bitartrate 700 mg by mouth daily | Drug: Choline bitartrate<br> <br> |
| Experimental: Betaine<br>Betaine 1000 mg by mouth daily | Drug: Betaine<br> <br> |
| Experimental: Choline bitartrate + Betaine<br>Choline bitartrate 700 mg + Betaine 1000 mg daily | Drug: Choline bitartrate + Betaine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary % Monomethyl Arsenic |  | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) | 
| Change in Urinary % Inorganic Arsenic |  | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) | 
| Change in Urinary % Dimethyl Arsenic |  | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
arsenic, Bangladesh, choline, betaine, methylation