Trial Outcomes & Findings for Dietary Supplements for the Treatment of Angelman Syndrome (NCT NCT00348933)

NCT ID: NCT00348933

Last Updated: 2012-09-24

Results Overview

Primary: Bayley Scales of Infant Development measures Mental Developmental Index standard scores 0 (least skilled) - 100 (most skilled) Psychomotor Developmental Index standard scores 0 (least skilled - 10 (most skilled) Vineland Adaptive Behavior Scales (VABS), Communication standard scores 0 (least skilled) - 100 (most skilled) Daily Living Skills standard scores 0 (least skilled) - 100 (most skilled) Socialization standard scores 0 (least skilled) - 100 (most skilled) Motor Skills standard scores 0 (least skilled) - 100 (most skilled) Preschool Language Scale (PLS), Auditory Comprehension 0 (least skilled) - 100 (most skilled) Expressive Communication 0 (least skilled) - 100 (most skilled)

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 90 participants
• Primary outcome timeframe: Baseline, 1 year
• Results posted on: 2012-09-24

Participant Flow

Participant milestones

Measure	Metafolin, Betaine, Creatine, B12 Treatment Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.
Overall Study STARTED	90
Overall Study COMPLETED	65
Overall Study NOT COMPLETED	25

Reasons for withdrawal

Measure	Metafolin, Betaine, Creatine, B12 Treatment Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.
Overall Study Withdrawal by Subject	10
Overall Study Lost to Follow-up	6
Overall Study Protocol Violation	2
Overall Study Adverse Event	7

Baseline Characteristics

Dietary Supplements for the Treatment of Angelman Syndrome

Baseline characteristics by cohort

Measure	Metafolin, Betaine, Creatine, B12 Treatment n=90 Participants Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.
Age, Categorical <=18 years	90 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	2.9 years STANDARD_DEVIATION 1.2 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants
Region of Enrollment United States	90 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 1 year

Population: Analysis per protocol

Primary:

Bayley Scales of Infant Development measures Mental Developmental Index standard scores 0 (least skilled) - 100 (most skilled) Psychomotor Developmental Index standard scores 0 (least skilled - 10 (most skilled) Vineland Adaptive Behavior Scales (VABS), Communication standard scores 0 (least skilled) - 100 (most skilled) Daily Living Skills standard scores 0 (least skilled) - 100 (most skilled) Socialization standard scores 0 (least skilled) - 100 (most skilled) Motor Skills standard scores 0 (least skilled) - 100 (most skilled) Preschool Language Scale (PLS), Auditory Comprehension 0 (least skilled) - 100 (most skilled) Expressive Communication 0 (least skilled) - 100 (most skilled)

Outcome measures

Measure	Treatment (Metafolin/Creatine/Betaine/B12) n=65 Participants
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills PLS Expressive Communication	5.5 units on a scale Standard Deviation 9.6
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills Bayley Scales Mental Developmental Index	5.7 units on a scale Standard Deviation 7.8
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills Bayley Scales Psychomotor Developmental Index	4.7 units on a scale Standard Deviation 8.6
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills VABS Communication	5.8 units on a scale Standard Deviation 8.3
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills VABS Daily Living Skills	3.7 units on a scale Standard Deviation 7.9
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills VABS Socialization	4.7 units on a scale Standard Deviation 5.2
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills VABS Motor Skills	2.0 units on a scale Standard Deviation 6.1
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills PLS Auditory Comprehension	2.0 units on a scale Standard Deviation 10.8

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: analysis per protocol

Outcome measures

Measure	Treatment (Metafolin/Creatine/Betaine/B12) n=65 Participants
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine. Betaine	206.9 mmol/L Standard Deviation 224.5
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine. Creatine	83.3 mmol/L Standard Deviation 165.9
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine. Dimethylglycine	93.7 mmol/L Standard Deviation 129
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine. Guanidinoacetate	0.11 mmol/L Standard Deviation 0.34
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine. Homocysteine	2.3 mmol/L Standard Deviation 2.1
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine. Methionine	5.5 mmol/L Standard Deviation 12.1

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: Analysis per protocol

Outcome measures

Measure	Treatment (Metafolin/Creatine/Betaine/B12) n=65 Participants
Change in RBC Folate	77 ng/mL Standard Deviation 267

Adverse Events

Metafolin, Betaine, Creatine, B12 Treatment

Serious events: 48 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Metafolin, Betaine, Creatine, B12 Treatment n=90 participants at risk Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.
Nervous system disorders Seizure	20.0% 18/90 • Number of events 18
General disorders Insomnia	15.6% 14/90 • Number of events 14
Gastrointestinal disorders Constipation	2.2% 2/90 • Number of events 2
Metabolism and nutrition disorders Anorexia	2.2% 2/90 • Number of events 2
Metabolism and nutrition disorders Increased appetite	1.1% 1/90 • Number of events 1
Psychiatric disorders Behavior disturbance	2.2% 2/90 • Number of events 2
Infections and infestations Infection	7.8% 7/90 • Number of events 7
Immune system disorders Serum sickness	1.1% 1/90 • Number of events 1
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome	1.1% 1/90 • Number of events 1

Other adverse events

Measure	Metafolin, Betaine, Creatine, B12 Treatment n=90 participants at risk Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.
General disorders Laboratory abnormalities	3.3% 3/90 • Number of events 3
Gastrointestinal disorders Diarrhea	1.1% 1/90 • Number of events 1
General disorders Body Odor	1.1% 1/90 • Number of events 1

Additional Information

Lynne M. Bird, MD

University of California and Rady Children's Hospital, San Diego

Phone: 858-966-5840

Email: Lbird@rchsd.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place