Clinical trial NCT04395196: RCT of Prenatal Choline Supplementation During Pregnancy to Mitigate Adverse Effects of Prenatal Alcohol Exposure
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Fetal Alcohol Spectrum Disorders
Fetal Alcohol Syndrome
Keywords: Prenatal Alcohol Exposure
Choline Supplementation
Infant Neurodevelopment
Growth
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: University of Cape Town
name: Columbia University
First posted: 2020-05-20
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Infant recognition memory
timeFrame: 12 months
measure: Postnatal infant weight gain
timeFrame: 6.5 months
measure: Postnatal growth in infant head circumference
timeFrame: 6.5 months
Secondary outcomes:
measure: Infant information processing speed
timeFrame: 12 months
measure: Postnatal growth in infant length
timeFrame: 6.5 months
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: University of Cape Town Faculty of Health Sciences
state: Western Cape
Study officials:
affiliation: Wayne State University
name: Sandra W Jacobson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Joseph L Jacobson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cape Town Faculty of Health Sciences
name: Ernesta M Meintjes, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University Vagelos College of Physicians and Surgeons
name: R. Colin Carter, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References: