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

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01749982
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 4
• Duration (Months): 20
• Patients Per Site Per Month: 3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arsenic Metabolites Measured in Urine	Other: Placebo; Drug: Choline bitartrate; Drug: Betaine; Drug: Choline bitartrate + Betaine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Pilot Study of Choline and Betaine Supplementation in Arsenic-exposed Individuals in Bangladesh
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo tablets	Other: Placebo
Experimental: Choline bitartrate Choline bitartrate 700 mg by mouth daily	Drug: Choline bitartrate
Experimental: Betaine Betaine 1000 mg by mouth daily	Drug: Betaine
Experimental: Choline bitartrate + Betaine Choline bitartrate 700 mg + Betaine 1000 mg daily	Drug: Choline bitartrate + Betaine

Outcome Measures

Primary Outcome Measures

1. Change in Urinary % Monomethyl Arsenic [From baseline to 8 weeks after the start of the intervention (week 8 - baseline)]

2. Change in Urinary % Inorganic Arsenic [From baseline to 8 weeks after the start of the intervention (week 8 - baseline)]

3. Change in Urinary % Dimethyl Arsenic [From baseline to 8 weeks after the start of the intervention (week 8 - baseline)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Arsenic Research Project	Dhaka		Bangladesh

Sponsors and Collaborators

• Columbia University

Investigators

• Principal Investigator: Megan N Hall, ScD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Megan Hall, Assistant Professor of Epidemiology, Columbia University
• ClinicalTrials.gov Identifier: NCT01749982
• Other Study ID Numbers: AAAJ1959
• First Posted: Dec 17, 2012
• Last Update Posted: Aug 28, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Megan Hall, Assistant Professor of Epidemiology, Columbia University: arsenic; Bangladesh; choline; betaine; methylation
• Additional relevant MeSH terms: Choline; Betaine

Study Results

Participant Flow

Arm/Group Title	Placebo	Choline Bitartrate	Betaine	Choline Bitartrate + Betaine
Arm/Group Description	Placebo tablets Placebo	Choline bitartrate 700 mg by mouth daily Choline bitartrate	Betaine 1000 mg by mouth daily Betaine	Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine
Period Title: Overall Study
STARTED	15	15	15	15
COMPLETED	15	15	15	12
NOT COMPLETED	0	0	0	3

Baseline Characteristics

Arm/Group Title	Placebo	Choline Bitartrate	Betaine	Choline Bitartrate + Betaine	Total
Arm/Group Description	Placebo tablets Placebo	Choline bitartrate 700 mg by mouth daily Choline bitartrate	Betaine 1000 mg by mouth daily Betaine	Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine	Total of all reporting groups
Overall Participants	15	15	15	15	60
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	30.0	34.0	29.0	32.0	31.0
Sex: Female, Male (Count of Participants)
Female	8 53.3%	8 53.3%	7 46.7%	7 46.7%	30 50%
Male	7 46.7%	7 46.7%	8 53.3%	8 53.3%	30 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	15 100%	15 100%	15 100%	15 100%	60 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	15 100%	15 100%	15 100%	15 100%	60 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Bangladesh	15 100%	15 100%	15 100%	15 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Change in Urinary % Monomethyl Arsenic
Time Frame	From baseline to 8 weeks after the start of the intervention (week 8 - baseline)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Choline Bitartrate	Betaine	Choline Bitartrate + Betaine
Arm/Group Description	Placebo tablets Placebo	Choline bitartrate 700 mg by mouth daily Choline bitartrate	Betaine 1000 mg by mouth daily Betaine	Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine
Measure Participants	15	15	15	12
Median (Full Range) [percentage of total urinary arsenic]	2.4	0.24	-0.06	-3.2

2. Primary Outcome

Title	Change in Urinary % Inorganic Arsenic
Time Frame	From baseline to 8 weeks after the start of the intervention (week 8 - baseline)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Choline Bitartrate	Betaine	Choline Bitartrate + Betaine
Arm/Group Description	Placebo tablets Placebo	Choline bitartrate 700 mg by mouth daily Choline bitartrate	Betaine 1000 mg by mouth daily Betaine	Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine
Measure Participants	15	15	15	12
Median (Full Range) [percentage of total urinary arsenic]	3.0	-0.87	-1.25	-1.7

3. Primary Outcome

Title	Change in Urinary % Dimethyl Arsenic
Time Frame	From baseline to 8 weeks after the start of the intervention (week 8 - baseline)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Choline Bitartrate	Betaine	Choline Bitartrate + Betaine
Arm/Group Description	Placebo tablets Placebo	Choline bitartrate 700 mg by mouth daily Choline bitartrate	Betaine 1000 mg by mouth daily Betaine	Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine
Measure Participants	15	15	15	12
Median (Full Range) [percentage of total urinary arsenic]	-5.8	0.65	-0.87	5.45

Adverse Events

Arm/Group Title	Placebo		Choline Bitartrate		Betaine		Choline Bitartrate + Betaine
Arm/Group Description	Placebo tablets Placebo		Choline bitartrate 700 mg by mouth daily Choline bitartrate		Betaine 1000 mg by mouth daily Betaine		Choline bitartrate 700 mg + Betaine 1000 mg daily Choline bitartrate + Betaine
All Cause Mortality
	Placebo		Choline Bitartrate		Betaine		Choline Bitartrate + Betaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Choline Bitartrate		Betaine		Choline Bitartrate + Betaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Choline Bitartrate		Betaine		Choline Bitartrate + Betaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)		5/15 (33.3%)		2/15 (13.3%)		2/15 (13.3%)
Gastrointestinal disorders
Diarrhea	2/15 (13.3%)		2/15 (13.3%)		0/15 (0%)		2/15 (13.3%)
General disorders
Fever	3/15 (20%)		2/15 (13.3%)		2/15 (13.3%)		0/15 (0%)
Chest pain	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)

Limitations/Caveats

This is a pilot study that is not powered to detect statistically significant effects. The results given here are descriptive.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.