Postnatal Choline Supplementation in Children With Prenatal Alcohol Exposure
Sponsor
University of Minnesota (Other)
Overall Status
Completed
CT.gov ID
NCT01149538
Collaborator
National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
60
1
2
50
1.2
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if choline bitartrate can be administered daily to children with prenatal alcohol exposure, ages 2.5 to 5, as a potential treatment for brain development and cognitive functioning.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Postnatal Choline Supplementation in Children With Prenatal Alcohol Exposure
Study Start Date
:
Jul 1, 2010
Actual Primary Completion Date
:
Sep 1, 2014
Actual Study Completion Date
:
Sep 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Choline Bitartrate Choline Bitartrate supplementation |
Drug: Choline bitartrate
Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix.
|
| Placebo Comparator: Placebo Placebo for choline bitartrate supplementation |
Dietary Supplement: Placebo for choline bitartrate
Placebo for choline bitartrate, administered daily in fruit-flavored drink mix.
|
Outcome Measures
Primary Outcome Measures
- Side Effects of Choline Bitartrate [Baseline, 6 months, & 9 months]
Side effects of choline bitartrate will be monitored by the study physician and the P.I. with physical examinations and telephone contact.
- Mullen Scales of Early Learning - Early Learning Composite [Baseline and 9 months]
The Mullen Scales of Early Learning is a measure of global cognitive development and is a primary outcome measure. The Early Learning Composite is the total score for this measure. It is a scaled score with a mean of 100 and a standard deviation of 15 (higher scores indicate better global cognitive status; average range is 85-115; Impaired range is 70 or below; full range is typically 50 - 150, although minimum and maximum scores are dependent on age). See the Mullen Scales reference manual for more psychometric details.
Secondary Outcome Measures
- Elicited Imitation Task Memory [Baseline, 6 months, and 9 months]
The Elicited Imitation (EI) paradigm (P.J. Bauer, 1989, Dev. Psychology) was used to measure memory in the participants at baseline, 6 months, and 9 months. The measures were items recalled after a delay (delayed items) and pairs of items recalled after a delay (delayed pairs). The sample was split by age in the analysis (young vs. old) as reflected in the outcome data. Outcome data measures included here are the slopes of the regression lines reflecting change over the three timepoints, controlling for immediate memory performance on the EI task.The slopes are given, as opposed to the raw scores, because these were the values used in the growth curve analyses. Details of these analyses are included in Wozniak et al. (2015) AJCN, doi:10.3945/ajcn.114.099168. NOTE that the means presented below represent the simple slopes that estimate the change in task performance (% of items correct) per 6-month unit of time. To estimate change in task performance over 9 months, multiply by 1.5.
- Evoked Response Potentials Microvolts [Baseline, 6 months, and 9 months]
Evoked response potentials were measured for the memory task. Frontal positive slow-wave potential negative component amplitude data are included.
- Evoked Response Potential - Negative Component Latency [Baseline, 6 months, and 9 months]
Evoked Response Potential - negative component latency data are included.
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 5 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Available parent or legal guardian capable of participating in informed consent process
-
Documented history of heavy prenatal alcohol exposure (self-report, social service records, or adoption records) or presence of facial dysmorphology characteristic of FASD or both
-
Evidence of cognitive deficit in at least one neurocognitive domain
Exclusion Criteria:
-
History of neurological condition (ex. epilepsy, cerebral palsy, traumatic brain injury)
-
History of medical condition known to affect brain function
-
History of other neurodevelopmental disorder (ex. autism, down syndrome)
-
History of very low birthweight (<1500 grams)
-
History of prenatal exposure to drugs other than alcohol, nicotine, and caffeine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Minnesota | Minneapolis | Minnesota | United States | 55454 |
Sponsors and Collaborators
- University of Minnesota
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
- Principal Investigator: Jeffrey R Wozniak, Ph.D., University of Minnesota
- Principal Investigator: Michael Georgieff, M.D., University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
University of Minnesota
ClinicalTrials.gov Identifier:
NCT01149538
Other Study ID Numbers:
- 0910M73517
- R21AA019580
First Posted:
Jun 23, 2010
Last Update Posted:
Dec 19, 2016
Last Verified:
Oct 1, 2016
Keywords provided by University of Minnesota
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Choline Bitartrate | Placebo |
|---|---|---|
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. |
| Period Title: Overall Study | ||
| STARTED | 31 | 29 |
| COMPLETED | 26 | 25 |
| NOT COMPLETED | 5 | 4 |
Baseline Characteristics
| Arm/Group Title | Choline Bitartrate | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. | Total of all reporting groups |
| Overall Participants | 31 | 29 | 60 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
3.79
(.80)
|
3.92
(.76)
|
3.855
(.78)
|
| Gender (Count of Participants) | |||
| Female |
19
61.3%
|
19
65.5%
|
38
63.3%
|
| Male |
12
38.7%
|
10
34.5%
|
22
36.7%
|
Outcome Measures
| Title | Side Effects of Choline Bitartrate |
|---|---|
| Description | Side effects of choline bitartrate will be monitored by the study physician and the P.I. with physical examinations and telephone contact. |
| Time Frame | Baseline, 6 months, & 9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Children with fetal alcohol spectrum disorders receiving either choline or placebo for 9 months |
| Arm/Group Title | Choline Bitartrate | Placebo |
|---|---|---|
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. |
| Measure Participants | 31 | 29 |
| Baseline energy level problems |
8
25.8%
|
10
34.5%
|
| 6 month energy level problems |
8
25.8%
|
9
31%
|
| 9 months energy level problems |
8
25.8%
|
9
31%
|
| Baseline pain |
3
9.7%
|
4
13.8%
|
| 6 month pain |
3
9.7%
|
4
13.8%
|
| 9 month pain |
3
9.7%
|
4
13.8%
|
| Baseline skin problems |
6
19.4%
|
6
20.7%
|
| 6 month skin problems |
6
19.4%
|
5
17.2%
|
| 9 month skin problems |
6
19.4%
|
5
17.2%
|
| Baseline Ear Nose Throat problems |
1
3.2%
|
0
0%
|
| 6 month Ear Nose Throat problems |
1
3.2%
|
0
0%
|
| 9 month Ear Nose Throat problems |
1
3.2%
|
1
3.4%
|
| Baseline headaches/dizziness |
2
6.5%
|
2
6.9%
|
| 6 month headaches/dizziness |
2
6.5%
|
2
6.9%
|
| 9 month headaches/dizziness |
2
6.5%
|
2
6.9%
|
| Baseline vision problems |
2
6.5%
|
2
6.9%
|
| 6 month vision problems |
0
0%
|
2
6.9%
|
| 9 month vision problems |
0
0%
|
2
6.9%
|
| Baseline cardiovascular |
1
3.2%
|
1
3.4%
|
| 6 month cardiovascular |
1
3.2%
|
1
3.4%
|
| 9 month cardiovascular |
1
3.2%
|
1
3.4%
|
| Baseline respiratory problems |
6
19.4%
|
6
20.7%
|
| 6 month respiratory problems |
6
19.4%
|
6
20.7%
|
| 9 month respiratory problems |
6
19.4%
|
6
20.7%
|
| Baseline gastrointestinal problems |
18
58.1%
|
14
48.3%
|
| 6 month gastrointestinal problems |
18
58.1%
|
11
37.9%
|
| 9 month gastrointestinal problems |
18
58.1%
|
11
37.9%
|
| Baseline genitourinary problems |
4
12.9%
|
9
31%
|
| 6 month genitourinary problems |
4
12.9%
|
8
27.6%
|
| 9 month genitourinary problems |
4
12.9%
|
8
27.6%
|
| Baseline musculoskeletal problems |
0
0%
|
1
3.4%
|
| 6 month musculoskeletal problems |
0
0%
|
1
3.4%
|
| 9 month musculoskeletal problems |
0
0%
|
1
3.4%
|
| 6 month neurologic/psychiatric problems |
11
35.5%
|
9
31%
|
| 9 month neurologic/psychiatric problems |
11
35.5%
|
9
31%
|
| Baseline neurologic/psychiatric problems |
11
35.5%
|
9
31%
|
| Baseline allergic problems |
2
6.5%
|
3
10.3%
|
| 6 month allergic problems |
0
0%
|
3
10.3%
|
| 9 month allergic problems |
0
0%
|
3
10.3%
|
| Title | Mullen Scales of Early Learning - Early Learning Composite |
|---|---|
| Description | The Mullen Scales of Early Learning is a measure of global cognitive development and is a primary outcome measure. The Early Learning Composite is the total score for this measure. It is a scaled score with a mean of 100 and a standard deviation of 15 (higher scores indicate better global cognitive status; average range is 85-115; Impaired range is 70 or below; full range is typically 50 - 150, although minimum and maximum scores are dependent on age). See the Mullen Scales reference manual for more psychometric details. |
| Time Frame | Baseline and 9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Including those with partial completion (drop-outs and lost-to-followup). |
| Arm/Group Title | Choline Bitartrate | Placebo |
|---|---|---|
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. |
| Measure Participants | 31 | 29 |
| Baseline |
83.2
(13.7)
|
84.3
(21.4)
|
| 9-month follow-up |
87.1
(16.4)
|
89.6
(21.6)
|
| Title | Elicited Imitation Task Memory |
|---|---|
| Description | The Elicited Imitation (EI) paradigm (P.J. Bauer, 1989, Dev. Psychology) was used to measure memory in the participants at baseline, 6 months, and 9 months. The measures were items recalled after a delay (delayed items) and pairs of items recalled after a delay (delayed pairs). The sample was split by age in the analysis (young vs. old) as reflected in the outcome data. Outcome data measures included here are the slopes of the regression lines reflecting change over the three timepoints, controlling for immediate memory performance on the EI task.The slopes are given, as opposed to the raw scores, because these were the values used in the growth curve analyses. Details of these analyses are included in Wozniak et al. (2015) AJCN, doi:10.3945/ajcn.114.099168. NOTE that the means presented below represent the simple slopes that estimate the change in task performance (% of items correct) per 6-month unit of time. To estimate change in task performance over 9 months, multiply by 1.5. |
| Time Frame | Baseline, 6 months, and 9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Young choline group (n=17); Young placebo group (n=13); Old choline group (n=14); Old placebo group (n=16). |
| Arm/Group Title | Choline Bitartrate | Placebo |
|---|---|---|
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. |
| Measure Participants | 31 | 29 |
| Delayed-Items-Young |
14.24
(3.84)
|
4.43
(4.04)
|
| Delayed-Items-Old |
-.71
(3.98)
|
4.23
(3.90)
|
| Delayed-Pairs-Young |
18.97
(3.65)
|
10.39
(4.00)
|
| Delayed-Pairs-Old |
2.69
(3.79)
|
7.79
(3.73)
|
| Immed-Items-Young |
8.48
(4.23)
|
13.72
(4.41)
|
| Immed-Items-Old |
2.59
(4.36)
|
3.89
(4.24)
|
| Immed-Pairs-Young |
8.75
(4.45)
|
20.01
(4.80)
|
| Immed-Pairs-Old |
11.46
(4.61)
|
5.50
(4.46)
|
| Title | Evoked Response Potentials Microvolts |
|---|---|
| Description | Evoked response potentials were measured for the memory task. Frontal positive slow-wave potential negative component amplitude data are included. |
| Time Frame | Baseline, 6 months, and 9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Children with FASD who were administered Evoked Response Potential test and provided usable date (choline and placebo arms) |
| Arm/Group Title | Choline Bitartrate | Placebo |
|---|---|---|
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. |
| Measure Participants | 36 | 35 |
| Frontal Positive Slow Wave (PSW) - Baseline |
-2.05
(5.49)
|
0.57
(7.24)
|
| Frontal Positive Slow Wave (PSW) - 6 months |
-1.04
(4.58)
|
-1.03
(3.48)
|
| Frontal Positive Slow Wave (PSW) - 9 months |
-0.26
(5.01)
|
-1.41
(5.23)
|
| Frontal Neg Component Amplitude - Baseline |
-2.53
(5.66)
|
0.62
(7.56)
|
| Frontal Neg Component Amplitude - 6 months |
1.22
(5.46)
|
-0.84
(4.94)
|
| Frontal Neg Component Amplitude - 9 months |
0.35
(5.53)
|
-1.37
(5.08)
|
| Title | Evoked Response Potential - Negative Component Latency |
|---|---|
| Description | Evoked Response Potential - negative component latency data are included. |
| Time Frame | Baseline, 6 months, and 9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Children with FASD who were administered Evoked Response Potential test and provided usable data (choline and placebo arms) |
| Arm/Group Title | Choline Bitartrate | Placebo |
|---|---|---|
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. |
| Measure Participants | 36 | 35 |
| Frontal Neg Component Latency at baseline |
2.23
(43.96)
|
5.35
(60.21)
|
| Frontal Neg Component at 6 months |
32.45
(60.31)
|
-4.28
(55.22)
|
| Frontal Neg Component at 9 months |
-4.00
(42.30)
|
-3.03
(79.62)
|
Adverse Events
| Time Frame | Adverse events reported here represent events EVER reported over the 9-month duration of the study. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events by organ system (percentage EVER reporting symptoms within each organ system listed - over 9 months). Events were collected in categories listed below (some include multiple symptoms). Individual symptom data exists in detailed notes for each participant but is not available in tallied form (except as aggregated into categories). | |||
| Arm/Group Title | Choline Bitartrate | Placebo | ||
| Arm/Group Description | Choline Bitartrate supplementation Choline bitartrate: Choline bitartrate 500 mg. daily, administered in fruit-flavored drink mix. | Placebo for choline bitartrate supplementation Placebo for choline bitartrate: Placebo for choline bitartrate, administered daily in fruit-flavored drink mix. | ||
All Cause Mortality |
||||
| Choline Bitartrate | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Choline Bitartrate | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/31 (0%) | 0/29 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Choline Bitartrate | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/31 (48.4%) | 13/29 (44.8%) | ||
| Cardiac disorders | ||||
| Cardiovascular | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Ear | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Gastrointestinal | 9/31 (29%) | 9 | 7/29 (24.1%) | 7 |
| Fishy Body Odor | 15/31 (48.4%) | 15 | 1/29 (3.4%) | 1 |
| Immune system disorders | ||||
| Allergy | 0/31 (0%) | 0 | 2/29 (6.9%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal | 0/31 (0%) | 0 | 0/29 (0%) | 0 |
| Nervous system disorders | ||||
| Neurologic | 6/31 (19.4%) | 6 | 4/29 (13.8%) | 4 |
| Renal and urinary disorders | ||||
| Genitourinary | 3/31 (9.7%) | 3 | 8/29 (27.6%) | 8 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory | 5/31 (16.1%) | 5 | 4/29 (13.8%) | 4 |
| Skin and subcutaneous tissue disorders | ||||
| Skip problems | 4/31 (12.9%) | 4 | 4/29 (13.8%) | 4 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jeffrey R. Wozniak, Ph.D. |
|---|---|
| Organization | University of Minnesota |
| Phone | 612-273-9741 |
| jwozniak@umn.edu |
Responsible Party:
University of Minnesota
ClinicalTrials.gov Identifier:
NCT01149538
Other Study ID Numbers:
- 0910M73517
- R21AA019580
First Posted:
Jun 23, 2010
Last Update Posted:
Dec 19, 2016
Last Verified:
Oct 1, 2016