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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo tablets |
|
| Choline bitartrate | Experimental | Choline bitartrate 700 mg by mouth daily |
|
| Betaine | Experimental | Betaine 1000 mg by mouth daily |
|
| Choline bitartrate + Betaine | Experimental | Choline bitartrate 700 mg + Betaine 1000 mg daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Other |
| ||
| Choline bitartrate |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Megan N Hall, ScD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Arsenic Research Project | Dhaka | Bangladesh |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo tablets Placebo |
| FG001 | Choline Bitartrate | Choline bitartrate 700 mg by mouth daily Choline bitartrate |
| FG002 | Betaine | Betaine 1000 mg by mouth daily Betaine |
| FG003 | Choline Bitartrate + Betaine | Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo tablets Placebo |
| BG001 | Choline Bitartrate | Choline bitartrate 700 mg by mouth daily Choline bitartrate |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Urinary % Monomethyl Arsenic | Posted | Median | Full Range | percentage of total urinary arsenic | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo tablets Placebo |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders |
This is a pilot study that is not powered to detect statistically significant effects. The results given here are descriptive.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Megan N Hall | Columbia University | 212-305-3161 | mh2825@columbia.edu |
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| ID | Term |
|---|---|
| D002794 | Choline |
| D001622 | Betaine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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|
| Betaine | Drug |
|
| Choline bitartrate + Betaine | Drug |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| BG002 | Betaine | Betaine 1000 mg by mouth daily Betaine |
| BG003 | Choline Bitartrate + Betaine | Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Choline Bitartrate + Betaine |
Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine |
|
|
| Primary | Change in Urinary % Inorganic Arsenic | Posted | Median | Full Range | percentage of total urinary arsenic | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) |
|
|
|
| Primary | Change in Urinary % Dimethyl Arsenic | Posted | Median | Full Range | percentage of total urinary arsenic | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) |
|
|
|
| 0 |
| 15 |
| 5 |
| 15 |
| EG001 | Choline Bitartrate | Choline bitartrate 700 mg by mouth daily Choline bitartrate | 0 | 15 | 5 | 15 |
| EG002 | Betaine | Betaine 1000 mg by mouth daily Betaine | 0 | 15 | 2 | 15 |
| EG003 | Choline Bitartrate + Betaine | Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine | 0 | 15 | 2 | 15 |
| Fever | General disorders |
|
| Chest pain | General disorders |
|
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| D000588 |
| Amines |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D009861 | Onium Compounds |