Maternal Choline Supplementation and Cannabis Use During Pregnancy: Impact on Early Brain Development

Clinical Trial of Maternal Choline Supplements to Mitigate Effects of Prenatal Cannabis Exposure on Early Brain Development

The goal of this study is to determine if providing a nutritional supplement, phosphatidylcholine, to pregnant women who have used cannabis products during the current pregnancy improves the offspring's brain-related development during the first 3 months. Participating pregnant women will receive either phosphatidylcholine or a placebo from approximately 16 weeks gestation through birth. The primary outcomes are the child's brain responses to sound at 4 weeks corrected age and infant behaviors at 3 months corrected age as reported by the primary caregiver. Secondary outcomes include motor, socio-emotional, language and cognitive development.

Study Overview

• Status: Recruiting
• Conditions: Child Development; Cannabis Use
• Intervention / Treatment: Drug: Choline; Drug: Placebo

Detailed Description

Phosphatidylcholine (PC) is a form of choline, a nutrient that is sometimes referred to as Vitamin B4 or Vitamin J. Choline is for normal growth everywhere in the body, including in the brain. PC is a naturally occurring substance and can be found in many different kinds of food including milk, liver, and eggs so most people get enough choline. However, when a woman is pregnant and her baby is growing many new cells, more PC may be needed. Research has suggested that the presence of adequate amounts of choline during pregnancy and breastfeeding can help ensure healthy fetal brain development and may have long-lasting positive effects on cognitive function. Problems in behavioral and cognitive development into childhood have been reported in children of mothers who used cannabis during gestation. Alternatively, two studies of maternal choline levels during pregnancy have reported beneficial effects of higher levels on childhood behavioral and cognitive development. This study assesses whether a higher dose of choline taken during pregnancy will have positive results on offspring development.

Participants in this double-blind study will be randomly assigned to receive either placebo or 1028 mg of choline daily throughout pregnancy, until delivery. Vital signs will be taken, potential side effects will be assessed, and study medication will be given at each visit. Blood samples will be taken at enrollment, and approximately at weeks 16, 22, 28, 34. Children will be followed and assessed until 3 months of age.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: M. Camille Hoffman, MD; Phone Number: 303-724-6205; Email: sharon.hunter@cuanschutz.edu
• Study Contact Backup: Name: Sharon Hunter, PhD; Phone Number: 303-724-6246; Email: sharon.hunter@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • UC Health
      • Contact: Sharon Hunter, PhD; Phone Number: 303-724-6246; Email: sharon.hunter@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant women who report cannabis use during current pregnancy

Exclusion Criteria:

• Pregnancies complicated by fetal anomaly, including neural tube defect or chromosomal abnormality, or multiple gestations due to increased obstetrical risks
• Women with major preexisting maternal medical morbidities
• Women with a prior history of fetal death
• Current personal history of chronic infections, including HIV
• Current personal or family history out to first-degree relatives of trimethylaminuria or homocystinuria
• Primary language other than English or Spanish
• Evidence of noncompliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will take 8 placebo capsules each containing 1100mg Rice Bran Oil and 150mg Pumpkin Seed Oil every day in place of phosphatidylcholine supplement.	Drug: Placebo; Pregnant women are instructed to take the capsules twice per day, 4 placebo capsules at breakfast and 4 placebo capsules at dinner. Increased awareness of the benefits of choline by obstetricians and pregnant women, as well as our published results from an observational study showing a wide distribution of plasma choline concentration, is a more apt independent variable for analyses.; Other Names: rice bran oil and pumpkin seed oil
Active Comparator: Phosphatidylcholine; Participants will take 8 900mg capsules of phosphatidylcholine every day, the equivalent of approximately 1028 mg of choline per day until delivery	Drug: Choline; Pregnant women are instructed to take the capsules twice per day, 4 900mg phosphatidylcholine capsules at breakfast and 4 capsules at dinner. Increased awareness Increased awareness of the benefits of choline by obstetricians and pregnant women, as well as our published results from an observational study showing a wide distribution of plasma choline concentration, is a more apt independent variable for analyses.; Other Names: Phosphatidylcholine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant Behavior Questionnaire-Revised (IBQ-R) Orienting/Regulation Index	The Orienting/Regulation Index is derived by adding the maternal rating of the infant's duration of attention, distractibility, soothability, cuddling, and smiling on the 91-item IBQ-r	3 months corrected age
Auditory Sensory Gating (P50)	Inhibition of the P50 cerebral auditory evoked response is collected during a paired stimulus auditory sensory gating paradigm	1 month corrected age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Child Behavior Checklist (CBCL) 1 1/2-5	The CBCL assesses a wide range of parent reported behaviors in children on a normative scale for comparison with others, including those assessed in need of clinical interventions for behavioral problems	18 months corrected age
Maternal Plasma Choline Levels	Plasma choline levels will be used to assess the effects of supplementation throughout gestation	approximately 16, 22, 28, 34 weeks gestation
Bayley Scales of Infant and Toddler Development	The Bayley Scales are a standardized assessment of language, cognitive and motor development	1, 3 and 6 months corrected age

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: M. Camille Hoffman, MD, University of Colorado, Denver; Principal Investigator: Sharon Hunter, PhD, University of Colorado School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2024
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: choline; phosphatidylcholine
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antimetabolites; Nootropic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Lipotropic Agents; Choline
• Other Study ID Numbers: 23-2327

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A copy of the locked database with all outcome, safety and demographic measures will be provided as a supplement to the primary publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No