RCT of Prenatal Choline Supplementation During Pregnancy to Mitigate Adverse Effects of Prenatal Alcohol Exposure

NCT ID: NCT04395196

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-13
• Study Completion Date: 2028-05-15

Brief Summary

Although the adverse effects associated with prenatal alcohol exposure (PAE) are well known, many women continue to drink heavily during pregnancy, putting their infants at risk for fetal alcohol spectrum disorders. Animal studies have shown that choline supplementation can mitigate effects of PAE on growth and development. Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. In an R21 feasibility trial, 70 heavy drinkers were randomly assigned to receive a daily dose of 2g of choline or a placebo from initiation of antenatal care to delivery in Cape Town, South Africa, where the incidence of heavy drinking during pregnancy and fetal alcohol syndrome are among the highest in the world. When compared with infants in the placebo arm, infants in the choline-treated arm were more likely to meet criterion for eyeblink conditioning, demonstrated markedly better recognition memory on the Fagan Test of Infant Intelligence, which is known to have predictive validity for school-age IQ, and had better postnatal gains in weight and head circumference. Key features of this study included the higher choline dose (4.4 times adequate intake (AI), compared to 1.7-2.5 in previous human studies) and initiation of treatment early in pregnancy. We are now conducting a fully-powered, double-blind, randomized, placebo-controlled choline supplementation trial in heavy drinking pregnant women from a rural community in South Africa (1) to assess the effectiveness of maternal choline supplementation during pregnancy to mitigate effects of PAE on three primary outcomes: infant recognition memory and postnatal growth restriction (weight and head circumference); (2) to assess the efficacy of this supplementation for mitigating alcohol effects on the following secondary outcomes: infant eyeblink conditioning, postnatal length, and information processing speed; (3) to use innovative methods in causal inference analysis to examine protocol adherence as an important source of variation in treatment efficacy and to identify sociodemographic factors associated with non-compliance in order to facilitate implementation of the intervention protocol in clinical settings; and (4) in exploratory analyses, to examine whether maternal choline supplementation is particularly effective in women with lower dietary choline intake or poor nutritional status.

Conditions

Fetal Alcohol Spectrum Disorders; Fetal Alcohol Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High-dose choline supplementation

2 g choline cation

Group Type: ACTIVE_COMPARATOR

Choline bitartrate

Intervention Type: DIETARY_SUPPLEMENT

Provided in beverage form

Placebo

Placebo identical to active treatment in appearance, taste, and smell.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Provided in beverage form

Interventions

Choline bitartrate

Provided in beverage form

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Provided in beverage form

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Age ≥18 yr
• ≤20 wk gestation
• Singleton pregnancy
• Currently heavy drinking (average of ≥15 ml AA/day or binge drinking (≥4 standard drinks/occasion) on at least 1.5 occasions/month on average since becoming pregnant)
• Current choline dietary intake <1 g/day
• Language fluency in English or Afrikaans

Exclusion Criteria

• Use of methamphetamine or other illicit drugs other than marijuana during the past year
• HIV positive
• Pharmacologic treatment for a serious pre-existing medical condition (e.g., diabetes, hypertension, epilepsy, or cardiac problems)
• Having another child enrolled in the trial from a previous pregnancy
• Plans for mother or child to move away from the area prior to study completion

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Cape Town

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: lead

Responsible Party

Sandra W. Jacobson, Ph.D

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sandra W Jacobson, PhD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Joseph L Jacobson, PhD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Ernesta M Meintjes, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town Faculty of Health Sciences

R. Colin Carter, MD, MMSc

Role: PRINCIPAL_INVESTIGATOR

Columbia University Vagelos College of Physicians and Surgeons

Locations

University of Cape Town Faculty of Health Sciences

Cape Town, Western Cape, South Africa

Site Status: RECRUITING

Countries

South Africa

Central Contacts

R. Colin Carter, MD, MMSc

Role: CONTACT

rcc2142@cumc.columbia.edu

+16176949902

Sandra W Jacobson, PhD

Role: CONTACT

sandra.jacobson@wayne.edu

+13139935454

Facility Contacts

Anthea Van Wyk

Role: primary

uctmoms@gmail.com

+27665643491

Ernesta Meintjes, PhD

Role: backup

ernesta.meintjes@gmail.com

Other Identifiers

R01AA028053

Identifier Type: NIH

Identifier Source: org_study_id

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