Choline Supplementation for Fetal Alcohol Spectrum Disorders

(CHOLINE4 Trial)

Overseen By Jeffrey R Wozniak, Ph.D.

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Jeff Wozniak

Disqualifiers: Neurological condition, Neurodevelopmental disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how choline supplementation can help children with Fetal Alcohol Spectrum Disorders (FASD) improve thinking and memory skills. Researchers are comparing two groups: one taking choline for 3 months and another for 6 months. The aim is to determine which duration more effectively boosts cognitive abilities. The trial seeks children aged 2.5 to 5 years who were exposed to alcohol before birth. Participants should not have other conditions, such as epilepsy or autism, that affect brain function. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

Is there any evidence suggesting that choline bitartrate is likely to be safe for humans?

Research has shown that choline supplements are generally safe for children. One study found that children aged 2 to 5 took 500 mg of choline daily for nine months without major issues, with most handling it well. Safety guidelines do not consider choline bitartrate dangerous, deeming it safe for use in food and supplements. Overall, evidence suggests that choline bitartrate is safe for children, with no significant side effects reported in similar studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for FASD?

Researchers are excited about choline bitartrate for fetal alcohol spectrum disorders (FASD) because it offers a new approach by potentially enhancing brain development and function. Unlike current treatments, which primarily focus on managing symptoms with behavioral therapies and medications, choline bitartrate directly targets brain health by providing a crucial nutrient that supports cognitive development. This nutrient may help mitigate some of the developmental challenges faced by individuals with FASD, offering hope for improved long-term outcomes.

What evidence suggests that choline supplementation might be an effective treatment for FASD?

Research has shown that choline can improve thinking skills in children with Fetal Alcohol Spectrum Disorders (FASD). Studies have found that children with FASD who took choline demonstrated better skills in speaking, memory, and understanding visual information. Early animal studies suggested that choline could reduce memory issues caused by prenatal alcohol exposure. Follow-up research has indicated that these positive effects on brain development can persist over time. In this trial, participants will receive either 6 months or 3 months of choline bitartrate, with the remaining months on placebo, to evaluate its effectiveness. Overall, choline appears to be a promising option for supporting brain development in children affected by FASD. ^{1 3 4 6 7}

Who Is on the Research Team?

Jeffrey R Wozniak, Ph.D.

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for children aged between 2.5 and 5 years who have been exposed to alcohol before birth and have a guardian able to consent. It's not for kids with conditions affecting brain function, other neurodevelopmental disorders like autism or Down syndrome, epilepsy, traumatic brain injuries, or those born weighing less than 1500 grams.

Inclusion Criteria

Prenatal alcohol exposure

I am between 2.5 and 5 years old.

Available parent or legal guardian capable of giving informed consent for participation

Exclusion Criteria

I have a history of a neurological condition.

I have a medical condition that affects my brain function.

Other neurodevelopmental disorder (e.g., autism, Down syndrome)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive choline bitartrate or placebo for a total of 9 months, with two dosing regimens: 3 months choline and 6 months placebo, or 6 months choline and 3 months placebo

9 months

Follow-up

Participants are monitored for cognitive and behavioral outcomes using various tests

9 months

What Are the Treatments Tested in This Trial?

Interventions

• Choline Bitartrate

Trial Overview The study tests if choline bitartrate supplements can help with cognitive development in kids with Fetal Alcohol Spectrum Disorders. It compares the effects of taking the supplement for either three months or six months in a randomized and double-blind setup.

How Is the Trial Designed?

Group I: 6 months choline bitartrate Experimental Treatment 1 Intervention

Over the 9-month study, participants will receive a total of 6 months of choline bitartrate (19 mg/kg) and a total of 3 months of placebo

Group II: 3 months choline bitartrate Experimental Treatment 1 Intervention

Over the 9-month study, participants will receive a total of 3 months of choline bitartrate (19 mg/kg) and a total of 6 months of placebo

Choline Bitartrate is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Choline Bitartrate for:

• Dietary Supplement
• Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders

Approved in Canada as Choline Bitartrate for:

• Dietary Supplement
• Neurodevelopmental Intervention

Approved in European Union as Choline Bitartrate for:

• Dietary Supplement
• Nutrient

Who Is Running the Clinical Trial?

Jeff Wozniak

Lead Sponsor

Trials

1

Recruited

60+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

Choline supplementation before alcohol exposure in mice significantly improved balance and coordination, suggesting it may help mitigate some negative effects of alcohol on the developing brain.

This study is the first to demonstrate that choline can counteract ethanol-induced deficits in motor function, highlighting the potential for choline fortification in diets to reduce risks associated with fetal alcohol exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline Ameliorates Deficits in Balance Caused by Acute Neonatal Ethanol Exposure. Bearer, CF., Wellmann, KA., Tang, N., et al.[2018]

Low maternal choline intake is linked to a higher risk of neural tube defects (NTDs), with a pooled estimate indicating a 36% increased odds for NTDs among mothers with low choline levels based on a meta-analysis of 5 case-control studies involving over 5,500 mothers.

Higher maternal choline intake during pregnancy (550 mg to 1 g/day) and early postnatal periods is associated with improved neurocognitive outcomes in children, suggesting that increasing choline intake could enhance memory, attention, and learning abilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Maternal Choline, Fetal Brain Development, and Child Neurocognition: Systematic Review and Meta-Analysis of Human Studies. Obeid, R., Derbyshire, E., Schön, C.[2023]

Choline supplementation shows promise as a potential intervention for cognitive deficits associated with fetal alcohol spectrum disorder (FASD), as it plays a crucial role in brain development and may help optimize cognitive function after prenatal alcohol exposure.

The review highlights existing preclinical and limited human studies that support the efficacy of choline in improving neurodevelopmental outcomes in children affected by FASD, while also addressing practical considerations for its supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder. Ernst, AM., Gimbel, BA., de Water, E., et al.[2022]

A phase I pilot study involving 20 children aged 2.5 to 4.9 years with fetal alcohol spectrum disorders (FASD) found that daily choline supplementation (500 mg) for 9 months was feasible and well tolerated, with high compliance rates of 82% to 87%.

The study reported minimal adverse effects, with the only notable side effect being fishy body odor in the choline group, and no serious adverse events occurred, suggesting that choline could be a safe option for further research in treating FASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability. Wozniak, JR., Fuglestad, AJ., Eckerle, JK., et al.[2021]

Choline supplementation can effectively reduce some learning impairments caused by fetal alcohol exposure, even when given after the exposure has occurred, suggesting its potential as a treatment for children with fetal alcohol spectrum disorders.

The study found that while the timing of choline administration had varying effects on spatial learning in rats, all choline treatments helped mitigate significant deficits in spatial memory caused by ethanol exposure, indicating a broad therapeutic window for choline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration. Ryan, SH., Williams, JK., Thomas, JD.[2021]

Choline supplementation during pregnancy has shown potential in preclinical studies to improve cognitive, behavioral, and neurological deficits in offspring exposed to alcohol, with significant benefits observed in various outcomes.

However, only one clinical study demonstrated notable improvements in infants' information processing, highlighting the need for more clinical trials to fully assess the effectiveness of choline in mitigating deficits from prenatal alcohol exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies. Akison, LK., Kuo, J., Reid, N., et al.[2019]

Choline supplementation during prenatal alcohol exposure significantly reduced the negative effects on birth weight, brain weight, and various behavioral developments in animal subjects, suggesting it may help mitigate some impacts of fetal alcohol spectrum disorders (FASD).

The study found that choline's protective effects were not due to changes in alcohol metabolism, indicating that it acts independently to improve outcomes for offspring exposed to alcohol in utero.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats. Thomas, JD., Abou, EJ., Dominguez, HD.[2022]

In a 9-month clinical trial involving 24 children with Fetal Alcohol Spectrum Disorder (FASD), choline supplementation was linked to improved recognition memory performance, as measured by a delayed recall task.

Neurophysiological assessments showed correlations between memory performance and specific brain activity patterns (event-related potentials), indicating that choline may influence cognitive function in children with FASD, although no significant differences were found between the choline and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurophysiological correlates of memory change in children with fetal alcohol spectrum disorders treated with choline. Fuglestad, AJ., Miller, NC., Fink, BA., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3815698/

Choline supplementation in children with Fetal Alcohol ... Choline supplementation in children with FASD is feasible and well-tolerated, with minimal adverse events, except for a fishy body odor in one case.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9529279/

Choline Supplementation as an Intervention for Fetal ... Specifically, they found that children with FASD who received choline had improved verbal and working memory, visual-spatial reasoning, memory for faces, and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02735473

Study Details | NCT02735473 | Choline Supplementation ... Pre-clinical data suggests that choline may attenuate the cognitive deficits caused by prenatal alcohol exposure (especially memory deficits). This study will ...

4. jneurodevdisorders.biomedcentral.com jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-022-09470-w

Long-term follow-up of a randomized controlled trial of choline ... We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01911299

Choline Supplementation in Children With Fetal Alcohol ... Similarly, choline supplementation improves cognitive outcomes among rats exposed to alcohol during development, even when administered postnatally and after ...

6. hfpappexternal.fda.gov hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=FoodSubstances&id=CHOLINEBITARTRATE

choline bitartrate - cfsanappsexternal.fda.gov Substances Added to Food (formerly EAFUS) CHOLINE BITARTRATE Definitions FEMA No.: The trade association, Flavor and Extract Manufacturers Association (FEMA),

7. jubilantingrevia.com jubilantingrevia.com/Uploads/image/1022imguf_sdsCholineBitartrate.pdf

Choline Bitartrate Safety Data Sheet Material is not classified as Hazardous according to Directive 67/548/EEC and (EC) No 1272/2008. Page 3. Choline Bitartrate. Safety Data Sheet. According to the ...