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

NCT04395196 | Recruiting Phase 2 DMC

• 1 other identifier: R01AA028053
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 1

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

Keywords

Prenatal Alcohol Exposure; Choline Supplementation; Infant Neurodevelopment; Growth

Outcome Measures

Primary Outcomes (3)

• Infant recognition memory

  Novelty preference from the Fagan Test of Infant Intelligence

  12 months

• Postnatal infant weight gain

  6.5 months

• Postnatal growth in infant head circumference

  6.5 months

Secondary Outcomes (2)

• Infant information processing speed

  12 months

• Postnatal growth in infant length

  6.5 months

Study Arms (2)

High-dose choline supplementation

ACTIVE COMPARATOR

2 g choline cation

Dietary Supplement: Choline bitartrate

Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Interventions

Choline bitartrate DIETARY_SUPPLEMENT

Provided in beverage form

High-dose choline supplementation

Placebo DIETARY_SUPPLEMENT

Provided in beverage form

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wayne State University: lead
• University of Cape Town: collaborator
• Columbia University: collaborator

Study Sites (1)

University of Cape Town Faculty of Health Sciences

Cape Town, Western Cape, 7925, South Africa

RECRUITING

MeSH Terms

Conditions

Fetal Alcohol Spectrum Disorders

Interventions

Choline

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds

Study Officials

• Sandra W Jacobson, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Joseph L Jacobson, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Ernesta M Meintjes, PhD

  University of Cape Town Faculty of Health Sciences

  PRINCIPAL INVESTIGATOR

• R. Colin Carter, MD, MMSc

  Columbia University Vagelos College of Physicians and Surgeons

  PRINCIPAL INVESTIGATOR

Central Study Contacts

R. Colin Carter, MD, MMSc

CONTACT

+16176949902; rcc2142@cumc.columbia.edu

Sandra W Jacobson, PhD

CONTACT

+13139935454; sandra.jacobson@wayne.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 20, 2020
• Study Start: April 13, 2023
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): May 15, 2028
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Per NIAAA policies, data will be made available for sharing with researchers 2 years after the end of the grant or 2 years after the end date of a no-cost-extension, if issued. The end date for data requests will be determined by NIAAA policies.
• Access Criteria: Per NIAAA guidelines, for research purposes, "investigators at institutions with a Federal Wide Assurance (FWA) will be able to gain access to NIAAADA data by submitting a data access request in accordance with applicable NIAAADA policies (see https://ndar.nih.gov/access.html for sample policies). Data requests will be reviewed and granted by an NIAAA Data Access Committee." The study protocol, statistical analysis plan, and analytic code may be shared by requests to PI Sandra W. Jacobson, PhD.

Locations

ZA (1)