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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether giving choline, a nutrient found in foods like eggs and meat, can help improve brain function in young children with Fetal Alcohol Spectrum Disorders (FASD). These children have cognitive issues due to alcohol exposure before birth. Choline might help their brains work better, especially for memory and thinking skills.

Will I have to stop taking my current medications?

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

What evidence supports the effectiveness of the treatment choline supplementation for fetal alcohol spectrum disorders?

Research shows that choline, an essential nutrient, can help improve memory and learning deficits in children with fetal alcohol spectrum disorders (FASD). Studies in both animals and humans suggest that choline supplementation can reduce some of the cognitive and behavioral problems caused by prenatal alcohol exposure. ^{1 2 3 4 5}

Is choline supplementation safe for humans, especially in children with fetal alcohol spectrum disorders?

Choline supplementation has been shown to be safe and well-tolerated in children with fetal alcohol spectrum disorders, with minimal adverse effects reported, such as a fishy body odor. No serious adverse events were observed in studies, indicating that choline is generally safe for human use. ^{2 4 5 6 7}

How does the drug Choline Bitartrate differ from other treatments for Fetal Alcohol Spectrum Disorders?

Choline Bitartrate is unique because it is an essential nutrient that directly supports brain development and has shown potential in improving cognitive and behavioral deficits associated with Fetal Alcohol Spectrum Disorders (FASD), unlike other treatments that may not target these specific brain functions. ^{1 3 4 7 8}

Research Team

Jeffrey R Wozniak, Ph.D.

Principal Investigator

University of Minnesota

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Neurophysiological correlates of memory change in children with fetal alcohol spectrum disorders treated with choline. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats. [2022]

5. Netherlands 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. England 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. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Choline Ameliorates Deficits in Balance Caused by Acute Neonatal Ethanol Exposure. [2018]