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

Fetal Alcohol Spectrum Disorders Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-controlled Clinical Trial of Choline Supplementation During Pregnancy to Mitigate Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Development

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04395196
• Other study ID #: R01AA028053
• Status: Recruiting
• Phase: Phase 2
• Start date: April 13, 2023
• Est. completion date: May 15, 2028

Study information

• Verified date: March 2024
• Source: Wayne State University
• Contact: R. Colin Carter, MD, MMSc
• Phone: +16176949902
• Email: rcc2142[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 288
• Est. completion date: May 15, 2028
• Est. primary completion date: October 15, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Fetal Alcohol Spectrum Disorders
• Fetal Alcohol Syndrome

Intervention

Dietary Supplement:
• Choline bitartrate
Provided in beverage form
• Placebo
Provided in beverage form

Locations

Country	Name	City	State
South Africa	University of Cape Town Faculty of Health Sciences	Cape Town	Western Cape

Sponsors (3)

Lead Sponsor	Collaborator
Wayne State University	Columbia University, University of Cape Town

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infant recognition memory	Novelty preference from the Fagan Test of Infant Intelligence	12 months
Primary	Postnatal infant weight gain		6.5 months
Primary	Postnatal growth in infant head circumference		6.5 months
Secondary	Infant information processing speed	Processing speed on the Fagan Test of Infant Intelligence	12 months
Secondary	Postnatal growth in infant length		6.5 months