Angelman SyndromeNCT00348933
Dietary Supplements for the Treatment of Angelman Syndrome
A study testing Betaine, Creatine and Metafolin in people with Angelman Syndrome and Nervous System Diseases, run by University of California, San Diego at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 day to 5 years
- Conditions the study is for
- Angelman Syndrome, Nervous System Diseases
- What is being tested?
- Betaine, Creatine and Metafolin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2006to Feb 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of AS
- In stable condition with relatively good control of seizures
- Willing to comply with treatment, study visit schedule, and study assessments
- Willing to take oral or G-tube medication
- Willing to be contacted monthly during the course of the study
- Parent or guardian willing to provide informed consent
Who cannot join
- History of liver or kidney disease
- Currently being treated for a serious acute illness
- Known hypersensitivity to any of the study drugs
- Received high-dose folate drug treatment in the 12 months prior to study entry
- Other significant medical problems, including those involving the liver, kidney, or heart
- Other comorbidities, genetic disorders, or extreme prematurity; children with autism are not excluded
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Children's Hospital Boston
Boston, Massachusetts
Greenwood Genetics Center
Greenwood, South Carolina
Baylor College of Medicine
Houston, Texas
Rady Children's Hospital San Diego
San Diego, California, 92123
About this study
Official title: Efficacy of a Therapeutic Treatment Trial in Angelman Syndrome
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.
Read the detailed description
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.
- Conditions
- Angelman Syndrome, Nervous System Diseases
- Being tested
- Betaine, Creatine, Metafolin, Vitamin B12
- Keywords
- Developmental Delay, Mental Retardation, Ataxia, Microcephaly, Seizures
- Medical subject headings
- Angelman Syndrome, Nervous System Diseases, Learning Disabilities, Intellectual Disability, Ataxia, Microcephaly, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BetaineDrug
100-200 mg per kg per day by mouth with a maximum of 6 grams divided in two daily doses
CreatineDrug
200 mg per kg per day with a daily maximum of 5 grams divided in two daily doses
MetafolinDrug
0.5 mg per kg per day by mouth with a maximum of 8 milligrams divided in two daily doses
Vitamin B12Drug
1 mg by mouth per day for all weights and ages
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months. Receives: Drug: Betaine; Drug: Creatine; Drug: Metafolin; Drug: Vitamin B12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline, 1 year
Secondary outcomes (2)
Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine.
Measured: Baseline, 1 year
Change in RBC Folate
Measured: Baseline, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2006 (estimated)
- Study startJul 2006
- Primary completionFeb 2010
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Baylor College of Medicine, Rady Children's Hospital, San Diego, Boston Children's Hospital, Greenwood Genetic Center, Rare Diseases Clinical Research Network
- Responsible party
- Principal investigator, Lynne M. Bird, University of California, San Diego
- Investigators
- Arthur L. Beaudet, MD, Principal investigator, Department of Molecular and Human Genetics, Baylor College of MedicineCarlos A. Bacino, MD, Principal investigator, Department of Molecular and Human Genetics, Baylor College of MedicineWen-Hann Tan, BMBS, Principal investigator, Harvard Medical School, Children's Hospital BostonLynne M. Bird, MD, Principal investigator, Division of Dysmorphology/Genetics, Children's Hospital San Diego, Department of Pediatrics, University of California, San DiegoSteven A. Skinner, MD, Principal investigator, Greenwood Genetic Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00348933
- Sponsor's protocol ID
- RDCRN 5204
- Status last verified
- Sep 2012
- First submitted
- 3 Jul 2006
- Last updated
- 24 Sep 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 1997 Jan;15(1):70-3. doi: 10.1038/ng0197-70.
PubMed 8988171Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff J. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A. 2006 Mar 1;140(5):413-8. doi: 10.1002/ajmg.a.31074.
PubMed 16470747Williams CA, Lossie A, Driscoll D; R.C. Phillips Unit. Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet. 2001 Jun 1;101(1):59-64. doi: 10.1002/ajmg.1316.
PubMed 11343340Han J, Bichell TJ, Golden S, Anselm I, Waisbren S, Bacino CA, Peters SU, Bird LM, Kimonis V. A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome. Orphanet J Rare Dis. 2019 Oct 22;14(1):232. doi: 10.1186/s13023-019-1216-0.
PubMed 31640736Bird LM, Tan WH, Bacino CA, Peters SU, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, Gentile JK, Glaze DG, Horowitz LT, Mohan KN, Nespeca MP, Sahoo T, Sarco D, Waisbren SE, Beaudet AL. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet A. 2011 Dec;155A(12):2956-63. doi: 10.1002/ajmg.a.34297. Epub 2011 Oct 14.
PubMed 22002941
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of a Therapeutic Treatment Trial in Angelman Syndrome
- ClinicalTrials.gov ID
- NCT00348933
- Acronym / sponsor ID
- RDCRN 5204
- Conditions
- Angelman Syndrome, Nervous System Diseases
- Keywords
- Developmental Delay, Mental Retardation, Ataxia, Microcephaly, Seizures
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Baylor College of Medicine, Rady Children's Hospital, San Diego, Boston Children's Hospital, Greenwood Genetic Center, Rare Diseases Clinical Research Network
- Study start
- Jul 2006
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 6 Jul 2006 (estimated)
- Results
- Posted 24 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Betaine, Drug: Creatine, Drug: Metafolin, Drug: Vitamin B12Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months. |
Who may qualify
- Ages
- 1 day to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Diagnosis of AS
- In stable condition with relatively good control of seizures
- Willing to comply with treatment, study visit schedule, and study assessments
- Willing to take oral or G-tube medication
- Willing to be contacted monthly during the course of the study
Key exclusion criteria (6 listed)
- History of liver or kidney disease
- Currently being treated for a serious acute illness
- Known hypersensitivity to any of the study drugs
- Received high-dose folate drug treatment in the 12 months prior to study entry
- Other significant medical problems, including those involving the liver, kidney, or heart
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Betaine100-200 mg per kg per day by mouth with a maximum of 6 grams divided in two daily doses | Drug | 1 |
| Creatine200 mg per kg per day with a daily maximum of 5 grams divided in two daily doses | Drug | 1 |
| Metafolin0.5 mg per kg per day by mouth with a maximum of 8 milligrams divided in two daily doses | Drug | 1 |
| Vitamin B121 mg by mouth per day for all weights and ages | Drug | 1 |
Primary outcome
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills
Time frame: Baseline, 1 year
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)
2 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8988171Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 1997 Jan;15(1):70-3. doi: 10.1038/ng0197-70.
- Background: PubMed 16470747Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff J. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A. 2006 Mar 1;140(5):413-8. doi: 10.1002/ajmg.a.31074.
- Background: PubMed 11343340Williams CA, Lossie A, Driscoll D; R.C. Phillips Unit. Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet. 2001 Jun 1;101(1):59-64. doi: 10.1002/ajmg.1316.
- Derived from this study: PubMed 31640736Han J, Bichell TJ, Golden S, Anselm I, Waisbren S, Bacino CA, Peters SU, Bird LM, Kimonis V. A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome. Orphanet J Rare Dis. 2019 Oct 22;14(1):232. doi: 10.1186/s13023-019-1216-0.
- Derived from this study: PubMed 22002941Bird LM, Tan WH, Bacino CA, Peters SU, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, Gentile JK, Glaze DG, Horowitz LT, Mohan KN, Nespeca MP, Sahoo T, Sarco D, Waisbren SE, Beaudet AL. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet A. 2011 Dec;155A(12):2956-63. doi: 10.1002/ajmg.a.34297. Epub 2011 Oct 14.
Related trials for Angelman Syndrome
RecruitingPhase 3
BEACON - Phase III Clinical Study of Rugonersen in Angelman Syndrome.
Angelman Syndrome
RecruitingPhase 3
CHAMPION: A Study to Evaluate the Efficacy and Safety of Obudanersen (ION582) in Children and Adults With Angelman Syndrome (AS)
Angelman Syndrome
RecruitingObservational study
A Natural History Study of Angelman Syndrome
Angelman Syndrome, Neurodevelopmental Conditions
Active, not recruitingPhase 3
REVEAL: A Phase 3 Study of Obudanersen (ION582) in Angelman Syndrome
Angelman Syndrome
Active, not recruiting
Web Intervention for Parents of Youth With Genetic Syndromes (WINGS)
Telomeric 22Q13 Monosomy Syndrome, Tuberous Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arthur L. Beaudet, MD principal investigator
Department of Molecular and Human Genetics, Baylor College of Medicine
Carlos A. Bacino, MD principal investigator
Department of Molecular and Human Genetics, Baylor College of Medicine
Wen-Hann Tan, BMBS principal investigator
Harvard Medical School, Children's Hospital Boston
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Betaine, Creatine and Metafolin in people with Angelman Syndrome and Nervous System Diseases, run by University of California, San Diego at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills (time frame: Baseline, 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00348933, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2012.