Fetal Alcohol Spectrum DisordersPhase 2NCT04395196
RCT of Prenatal Choline Supplementation During Pregnancy to Mitigate Adverse Effects of Prenatal Alcohol Exposure
A Phase 2 study testing Choline bitartrate in people with Fetal Alcohol Spectrum Disorders and Fetal Alcohol Syndrome, run by Wayne State University at 1 site in South Africa.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Fetal Alcohol Spectrum Disorders, Fetal Alcohol Syndrome
- What is being tested?
- Choline bitartrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 288 participants
- Where
- 1 siteSouth Africa
- Study dates
- 13 Apr 2023to 15 May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Africa1 site, 1 recruiting
- Recruiting
University of Cape Town Faculty of Health Sciences
Cape Town, Western Cape, 7925
Anthea Van Wyk, +27665643491, uctmoms@gmail.com
Ernesta Meintjes, PhD, ernesta.meintjes@gmail.com
About this study
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
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.
- Being tested
- Choline bitartrate, Placebo
- Keywords
- Prenatal Alcohol Exposure, Choline Supplementation, Infant Neurodevelopment, Growth
- Medical subject headings
- Fetal Alcohol Spectrum Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Choline bitartrateDietary supplement
Provided in beverage form
PlaceboDietary supplement
Provided in beverage form
| Study group | Role | What they receive |
|---|---|---|
| High-dose choline supplementation | Active comparator | 2 g choline cation Receives: Dietary Supplement: Choline bitartrate |
| Placebo | Placebo comparator | Placebo identical to active treatment in appearance, taste, and smell. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infant recognition memory
Novelty preference from the Fagan Test of Infant Intelligence
Measured: 12 months
Postnatal infant weight gain
Measured: 6.5 months
Postnatal growth in infant head circumference
Measured: 6.5 months
Secondary outcomes (2)
Infant information processing speed
Processing speed on the Fagan Test of Infant Intelligence
Measured: 12 months
Postnatal growth in infant length
Measured: 6.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2020
- Study start13 Apr 2023
- Primary completion15 Oct 2027 (estimated)
- Study completion15 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fetal Alcohol Spectrum DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 288 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cape Town, Columbia University
- Responsible party
- Principal investigator, Sandra W. Jacobson, Ph.D, Wayne State University
- Investigators
- Sandra W Jacobson, PhD, Principal investigator, Wayne State UniversityJoseph L Jacobson, PhD, Principal investigator, Wayne State UniversityErnesta M Meintjes, PhD, Principal investigator, University of Cape Town Faculty of Health SciencesR. Colin Carter, MD, MMSc, Principal investigator, Columbia University Vagelos College of Physicians and Surgeons
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04395196
- Sponsor's protocol ID
- R01AA028053
- Status last verified
- Jul 2026
- First submitted
- 15 May 2020
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will make data collected in this study publicly available in accordance with the policies laid out in the NIH/National Institute on Alcohol Abuse and Alcoholism (NIAAA) Data-Sharing Policy for Human Subjects Grants Research Funded by the NIAAA (NOT-AA-18-010; https://grants.nih.gov/grants/guide/notice-files/NOT-AA-18- 010.html). Individual participant data relating to the chief aims of this study data obtained with NIAAA funding will be uploaded to the NIAAA Data Archive (NIAAADA). Only de-identified data will be available to the NIAAADA. A data dictionary will also be available.
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04395196
- Acronym / sponsor ID
- R01AA028053
- Keywords
- Prenatal Alcohol Exposure, Choline Supplementation, Infant Neurodevelopment, Growth
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 288 participants (estimated)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Collaborators
- University of Cape Town, Columbia University
- Study start
- 13 Apr 2023 (actual)
- Primary completion
- 15 Oct 2027 (estimated)
- Study completion
- 15 May 2028 (estimated)
- First posted
- 20 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-dose choline supplementation | Active comparator | Dietary Supplement: Choline bitartrate2 g choline cation |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo identical to active treatment in appearance, taste, and smell. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Choline bitartrateProvided in beverage form | Dietary supplement | High-dose choline supplementation |
| PlaceboProvided in beverage form | Dietary supplement | Placebo |
Primary outcome
Infant recognition memory
Time frame: 12 months
Novelty preference from the Fagan Test of Infant Intelligence
Postnatal infant weight gain
Time frame: 6.5 months
Postnatal growth in infant head circumference
Time frame: 6.5 months
2 secondary outcomes
Infant information processing speed
Time frame: 12 months
Postnatal growth in infant length
Time frame: 6.5 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Individual participant dataSharing planned: Yes. We will make data collected in this study publicly available in accordance with the policies laid out in the NIH/National Institute on Alcohol Abuse and Alcoholism (NIAAA) Data-Sharing Policy for Human Subjects Grants Research Funded by the NIAAA (NOT-AA-18-010; https://grants.nih.gov/grants/guide/notice-files/NOT-AA-18- 010.html). Individual participant data relating to the chief aims of this study data obtained with NIAAA funding will be uploaded to the NIAAA Data Archive (NIAAADA). Only de-identified data will be available to the NIAAADA. A data dictionary will also be available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sandra W Jacobson, PhD principal investigator
Wayne State University
Joseph L Jacobson, PhD principal investigator
Wayne State University
Ernesta M Meintjes, PhD principal investigator
University of Cape Town Faculty of Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Choline bitartrate in people with Fetal Alcohol Spectrum Disorders and Fetal Alcohol Syndrome, run by Wayne State University at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact R. Colin Carter, MD, MMSc (+16176949902, rcc2142@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infant recognition memory (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.