Fetal Alcohol Spectrum Disorders
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled trial of choline supplementation in children with Fetal Alcohol Spectrum Disorders (FASD). The primary outcome measures are cognitive measures.
Detailed description
This project is the third in a series of randomized, double-blind placebo-controlled trials of choline bitartrate in children ages 2-5 who have been diagnosed with Fetal Alcohol Spectrum Disorders (FASD). Pre-clinical data suggests that choline may attenuate the cognitive deficits caused by prenatal alcohol exposure (especially memory deficits). This study will evaluate the effects of daily choline supplementation vs. placebo for 9 months. Outcome measures include an elicited imitation memory paradigm, global cognitive functioning, and aspects of executive functioning. The study will also continue to collect safety and tolerability data.
Interventions
DRUGPlacebo
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 2 years to 5 years of age 2. Available parent or legal guardian capable of giving informed consent for participation. 3. Documented prenatal alcohol exposure (self-report, social service records, or adoption records). 4. Modified Institute of Medicine (IOM) criteria for Fetal Alcohol Syndrome (FAS), Partial Fetal Alcohol Syndrome (PFAS), or Alcohol-Related Neurodevelopmental Disorder (ARND) (Hoyme, May, et al., 2005).
Exclusion criteria
1. Known history of a neurological condition (ex. epilepsy, traumatic brain injury) 2. Known history of a medical condition known to affect brain function. 3. Known history of other neurodevelopmental disorder (ex. autism, Down syndrome) 4. Known history of very low birthweight (\<1500 grams)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Elicited Imitation Memory Task - Short Delay Memory Measure: 6 Months | Change from baseline to 6 months in percentage correct | Elicited Imitation memory paradigm - short delay memory measure at 6 months; scores are in percentage correct. |
| Elicited Imitation Memory Task - Short Delay Memory Measure: 9 Months | Change from baseline to 9 months | Elicited Imitation memory paradigm - short delay memory measure at 9 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minnesota Executive Function Scale: 9 Months | Change from baseline to 9 months in t-score points | Minnesota Executive Function Scale - Early Childhood Version at 9 months; scores are in t-scores (mean=50, standard deviation=10) |
| NIH Toolbox Flanker Task: 9 Months | Change from baseline to 9 months in fully-corrected t-score points | NIH Toolbox Flanker Inhibitory and Control Task at 9 months; scores are fully-corrected t-scores (mean=40, standard deviation=10) |
| Stanford-Binet Intelligence Scales: 9 Months | Change from baseline to 9 months in IQ points | Stanford-Binet Intelligence Scales at 9 months; scores are standardized scores (mean 100 points, standard deviation of 15 points) |
| Child Behavior Checklist: 6 Months | Change from baseline to 6 months | Child Behavior Checklist - parent report instrument at 6 months |
| Child Behavior Checklist: 9 Months | Change from baseline to 9 months in t-score points | Child Behavior Checklist - parent report instrument at 9 months; scores are t-scores (mean=50, standard deviation=10) |
| NIH Toolbox Flanker Task: 6 Months | Change from baseline to 6 months | NIH Toolbox Flanker Inhibitory and Control Task at 6 months |
| Minnesota Executive Function Scale: 6 Months | Change from baseline to 6 months | Minnesota Executive Function Scale - Early Childhood Version at 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Choline Bitartrate Powdered drink mix containing choline bitartrate 19 mg. per kg.
Choline bitartrate | 17 |
| Placebo Powdered drink mix containing matching placebo
Placebo | 16 |
| Total | 33 |
Baseline characteristics
| Characteristic | Choline Bitartrate | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 16 Participants | 33 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 17 / 23 | 16 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Elicited Imitation Memory Task - Short Delay Memory Measure: 6 Months
Elicited Imitation memory paradigm - short delay memory measure at 6 months; scores are in percentage correct.
Time frame: Change from baseline to 6 months in percentage correct
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Choline Bitartrate | Elicited Imitation Memory Task - Short Delay Memory Measure: 6 Months | 0.252 change in percentage correct | Standard Deviation 0.578 |
| Placebo | Elicited Imitation Memory Task - Short Delay Memory Measure: 6 Months | 0.183 change in percentage correct | Standard Deviation 0.213 |
Primary
Elicited Imitation Memory Task - Short Delay Memory Measure: 9 Months
Elicited Imitation memory paradigm - short delay memory measure at 9 months
Time frame: Change from baseline to 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Choline Bitartrate | Elicited Imitation Memory Task - Short Delay Memory Measure: 9 Months | 0.318 change in percentage correct | Standard Deviation 0.126 |
| Placebo | Elicited Imitation Memory Task - Short Delay Memory Measure: 9 Months | 0.668 change in percentage correct | Standard Deviation 0.372 |
Secondary
Child Behavior Checklist: 6 Months
Child Behavior Checklist - parent report instrument at 6 months
Time frame: Change from baseline to 6 months
Population: This measure was not collected at the 6-month visit. It was collected at the 9-month visit.
Secondary
Child Behavior Checklist: 9 Months
Child Behavior Checklist - parent report instrument at 9 months; scores are t-scores (mean=50, standard deviation=10)
Time frame: Change from baseline to 9 months in t-score points
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Choline Bitartrate | Child Behavior Checklist: 9 Months | -1.9 Change from baseline in t-score points | Standard Deviation 8.9 |
| Placebo | Child Behavior Checklist: 9 Months | -1.8 Change from baseline in t-score points | Standard Deviation 7.35 |
Secondary
Minnesota Executive Function Scale: 6 Months
Minnesota Executive Function Scale - Early Childhood Version at 6 months
Time frame: Change from baseline to 6 months
Population: This measure was not collected at the 6-month visit but was completed at the 9-month visit.
Secondary
Minnesota Executive Function Scale: 9 Months
Minnesota Executive Function Scale - Early Childhood Version at 9 months; scores are in t-scores (mean=50, standard deviation=10)
Time frame: Change from baseline to 9 months in t-score points
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Choline Bitartrate | Minnesota Executive Function Scale: 9 Months | 0.007 Percentage change in overall score | Standard Deviation 0.091 |
| Placebo | Minnesota Executive Function Scale: 9 Months | 0.017 Percentage change in overall score | Standard Deviation 0.177 |
Secondary
NIH Toolbox Flanker Task: 6 Months
NIH Toolbox Flanker Inhibitory and Control Task at 6 months
Time frame: Change from baseline to 6 months
Population: This measure was not collected at the 6-month visit. It was, however, collected at the 9-month visit.
Secondary
NIH Toolbox Flanker Task: 9 Months
NIH Toolbox Flanker Inhibitory and Control Task at 9 months; scores are fully-corrected t-scores (mean=40, standard deviation=10)
Time frame: Change from baseline to 9 months in fully-corrected t-score points
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Choline Bitartrate | NIH Toolbox Flanker Task: 9 Months | 0.091 Percentage change in fully-corrected t-s | Standard Deviation 0.372 |
| Placebo | NIH Toolbox Flanker Task: 9 Months | -0.169 Percentage change in fully-corrected t-s | Standard Deviation 0.641 |
Secondary
Stanford-Binet Intelligence Scales: 9 Months
Stanford-Binet Intelligence Scales at 9 months; scores are standardized scores (mean 100 points, standard deviation of 15 points)
Time frame: Change from baseline to 9 months in IQ points
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Choline Bitartrate | Stanford-Binet Intelligence Scales: 9 Months | 0.198 Percentage change in full-scale IQ point | Standard Deviation 0.175 |
| Placebo | Stanford-Binet Intelligence Scales: 9 Months | 0.008 Percentage change in full-scale IQ point | Standard Deviation 0.172 |