Dietary Supplements for the Treatment of Angelman Syndrome

NCT00348933 | Completed Results DMC

• 1 other identifier: RDCRN 5204
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Angelman Syndrome; Nervous System Diseases

Keywords

Developmental Delay; Mental Retardation; Ataxia; Microcephaly; Seizures

Outcome Measures

Primary Outcomes (1)

• 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)

  Baseline, 1 year

Secondary Outcomes (2)

• Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine.

  Baseline, 1 year

• Change in RBC Folate

  Baseline, 1 year

Study Arms (1)

1

EXPERIMENTAL

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

Interventions

Betaine DRUG

100-200 mg per kg per day by mouth with a maximum of 6 grams divided in two daily doses

1

Creatine DRUG

200 mg per kg per day with a daily maximum of 5 grams divided in two daily doses

1

Metafolin DRUG

0.5 mg per kg per day by mouth with a maximum of 8 milligrams divided in two daily doses

1

Vitamin B12 DRUG

1 mg by mouth per day for all weights and ages

1

Eligibility Criteria

• Age: 1 Day - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• Baylor College of Medicine: collaborator
• Rady Children's Hospital, San Diego: collaborator
• Boston Children's Hospital: collaborator
• Greenwood Genetic Center: collaborator
• Rare Diseases Clinical Research Network: collaborator

Study Sites (4)

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

Children's Hospital Boston

Boston, Massachusetts, United States

Location

Greenwood Genetics Center

Greenwood, South Carolina, United States

Location

Baylor College of Medicine

Houston, Texas, United States

Location

Related Publications (5)

• 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.

  PMID: 8988171 BACKGROUND

• Williams 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.

  PMID: 16470747 BACKGROUND

• Williams 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.

  PMID: 11343340 BACKGROUND

• Han 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.

  PMID: 31640736 DERIVED

• Bird 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.

  PMID: 22002941 DERIVED

MeSH Terms

Conditions

Angelman Syndrome; Nervous System Diseases; Learning Disabilities; Intellectual Disability; Ataxia; Microcephaly; Seizures

Interventions

Betaine; Creatine; levomefolate calcium; Vitamin B 12

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Guanidines; Amidines; Amino Acids; Amino Acids, Peptides, and Proteins; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Lynne M. Bird, MD
• Organization: University of California and Rady Children's Hospital, San Diego

Lbird@rchsd.org

858-966-5840

Study Officials

• Arthur L. Beaudet, MD

  Department of Molecular and Human Genetics, Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Carlos A. Bacino, MD

  Department of Molecular and Human Genetics, Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Wen-Hann Tan, BMBS

  Harvard Medical School, Children's Hospital Boston

  PRINCIPAL INVESTIGATOR

• Lynne M. Bird, MD

  Division of Dysmorphology/Genetics, Children's Hospital San Diego, Department of Pediatrics, University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Steven A. Skinner, MD

  Greenwood Genetic Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 3, 2006
• First Posted: July 6, 2006
• Study Start: July 1, 2006
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: September 24, 2012
• Results First Posted: September 24, 2012

Record last verified: 2012-09

Locations

US (4)