An interventional study of Betaine and Creatine in Angelman Syndrome and Nervous System Diseases, sponsored by University of California, San Diego. Completed at 4 sites in United States. Open to participants aged 1 Day to 5 Years. Per ClinicalTrials.gov, last updated 2012-09-24.
Sponsored by University of California, San Diego · Not applicable, Interventional, and Treatment
Angelman syndrome (AS) is a complex genetic disorder that affects the nervous system. The purpose of this study is to determine the effectiveness of certain dietary supplements in treating the symptoms of AS.
AS is a neurologic disorder that may cause developmental delay, mental retardation, severe speech impairment, seizures, small head size, and problems with movement and balance in young children. AS is caused by a missing or incomplete chromosome 15 that is inherited from the mother. Diagnosis of AS is usually made between three and seven years of age, when the characteristic behaviors and features of the disease become most evident. Prior to AS diagnosis, the symptoms may be mistaken for cerebral palsy or autism. Physical, occupational, and speech therapy, communication skills development, and behavior modification help to improve the quality of life of these children, but other treatments are needed.
In a previous study, decreased DNA methylation, which is a type of chemical change in DNA, was observed in an individual with AS; this condition may be a primary cause of AS. It is hypothesized that promoting increased DNA methylation might reduce the severity of AS symptoms. Betaine, creatine, Metafolin, and vitamin B12 are compounds normally found in the body that are involved in the DNA methylation pathway. Increasing the concentrations of these compounds in the body may enhance DNA methylation. This study will evaluate the efficacy of four dietary supplements in treating the symptoms of AS.
This study will last 12 months. Study visits will occur at study entry and Month 12. A selected group of participants, those who meet the diagnostic criteria for autism, will also be evaluated at Month 6. At study visits, participants will undergo an electroencephalogram (EEG). Medical history, physical exam, neurological exams, and developmental assessments will also be performed. Urine and blood collection, including tests to determine the blood levels of the dietary supplements, will occur at study entry and Months 6 and 12. Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for the duration of the study. Parents will be asked to complete a questionnaire at each visit to report their child's behavior while taking the dietary supplements. Parents will also be contacted by phone periodically to assess changes and/or progress in their children.
48 studies on the registry are indexed under Angelman Syndrome; 16 are open to participants now.
This study's enrollment of 90 is above the median of 67 across 27 interventional studies indexed under Angelman Syndrome.
Browse Angelman Syndrome studies →University of California, San Diego is the lead sponsor of 975 studies on the registry; 196 are open to participants now.
Of its 111 completed or terminated interventional studies of FDA-regulated products, 71 (64%) have results posted.
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Exclusion Criteria:
Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.
Drug: Betaine · Drug: Creatine · Drug: Metafolin · Drug: Vitamin B12
100-200 mg per kg per day by mouth with a maximum of 6 grams divided in two daily doses
200 mg per kg per day with a daily maximum of 5 grams divided in two daily doses
0.5 mg per kg per day by mouth with a maximum of 8 milligrams divided in two daily doses
1 mg by mouth per day for all weights and ages
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills
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)
Time frame: Baseline, 1 year
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine.
Time frame: Baseline, 1 year
Change in RBC Folate
Time frame: Baseline, 1 year
| Milestone | Metafolin, Betaine, Creatine, B12 Treatment |
|---|---|
| Started | 90 |
| Completed | 65 |
| Not completed | 25 |
| Withdrew: Withdrawal by subject | 10 |
| Withdrew: Lost to follow-up | 6 |
| Withdrew: Protocol violation | 2 |
| Withdrew: Adverse event | 7 |
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)
| units on a scale | Treatment (Metafolin/Creatine/Betaine/B12) |
|---|---|
| Bayley Scales Mental Developmental Index | 5.7 ± 7.8 |
| Bayley Scales Psychomotor Developmental Index | 4.7 ± 8.6 |
| VABS Communication | 5.8 ± 8.3 |
| VABS Daily Living Skills | 3.7 ± 7.9 |
| VABS Socialization | 4.7 ± 5.2 |
| VABS Motor Skills | 2.0 ± 6.1 |
| PLS Auditory Comprehension | 2.0 ± 10.8 |
| PLS Expressive Communication | 5.5 ± 9.6 |
| mmol/L | Treatment (Metafolin/Creatine/Betain/B12) |
|---|---|
| Betaine | 206.9 ± 224.5 |
| Creatine | 83.3 ± 165.9 |
| Dimethylglycine | 93.7 ± 129 |
| Guanidinoacetate | 0.11 ± 0.34 |
| Homocysteine | 2.3 ± 2.1 |
| Methionine | 5.5 ± 12.1 |
| ng/mL | Treatment (Metafolin/Creatine/Betaine/B12) |
|---|---|
| Change in RBC Folate | 77 ± 267 |
Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metafolin, Betaine, Creatine, B12 Treatment | — | 48/90 (53.3%) | 5/90 (5.6%) |
| Event | Metafolin, Betaine, Creatine, B12 Treatment |
|---|---|
| SeizureNervous system disorders | 18/90 |
| InsomniaGeneral disorders | 14/90 |
| InfectionInfections and infestations | 7/90 |
| ConstipationGastrointestinal disorders | 2/90 |
| AnorexiaMetabolism and nutrition disorders | 2/90 |
| Behavior disturbancePsychiatric disorders | 2/90 |
| Increased appetiteMetabolism and nutrition disorders | 1/90 |
| Serum sicknessImmune system disorders | 1/90 |
| Adult Respiratory Distress SyndromeRespiratory, thoracic and mediastinal disorders | 1/90 |
| Event | Metafolin, Betaine, Creatine, B12 Treatment |
|---|---|
| Laboratory abnormalitiesGeneral disorders | 3/90 |
| DiarrheaGastrointestinal disorders | 1/90 |
| Body OdorGeneral disorders | 1/90 |
| Age, Categorical(Participants) | Metafolin, Betaine, Creatine, B12 Treatment |
|---|---|
| <=18 years | 90 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age Continuous(years) | Metafolin, Betaine, Creatine, B12 Treatment |
|---|---|
| Mean | 2.9 ± 1.2 |
| Sex: Female, Male(Participants) | Metafolin, Betaine, Creatine, B12 Treatment |
|---|---|
| Female | 43 |
| Male | 47 |
| Region of Enrollment(participants) | Metafolin, Betaine, Creatine, B12 Treatment |
|---|---|
| United States | 90 |
The record gives a start of Jul 2006, a primary completion of Feb 2010 and a completion of Feb 2010. It does not say whether these dates are actual or estimated.
Results were first posted in Sep 2012, 2 years 7 months after primary completion.
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Studies of the drugs tested here: Betaine · Creatine · Levomefolate calcium · Vitamin B 12
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