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Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2004 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00069550
First received: September 29, 2003
Last updated: June 23, 2005
Last verified: December 2004

September 29, 2003
June 23, 2005
September 2004
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Complete list of historical versions of study NCT00069550 on ClinicalTrials.gov Archive Site
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Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome
Pathogenesis of Rett Syndrome: Natural History and Treatment

Rett syndrome (RTT) is a disorder in which the nervous system does not develop properly. RTT generally affects girls, but there are some boys who have been diagnosed with RTT. Symptoms of RTT include small brain size, poor language skills, repetitive hand movements, and seizures. This study will evaluate the effectiveness of two drugs in treating the symptoms of RTT.

RTT is a neurodevelopmental disorder characterized by apparently normal early development followed by loss of purposeful hand use, distinctive hand stereotypies, slowed brain growth, loss of language, respiratory irregularities, GI disturbances, gait abnormalities, seizures, and mental retardation. These symptoms appear between ages 6 and 18 months (stage 2 of the disease) following apparently normal development (stage 1). Subsequently, there is gradual stabilization of severe mental retardation and motor compromise (stage 3). The majority (70% to 80%) of patients demonstrate mutations in the methyl-CpG-binding-protein-2 (MeCP2) gene, a transcription repressor located on chromosome Xq28. The disorder predominantly affects females, but a few males with mutations in MeCP2 have been identified, even though many of them do not have the classic symptoms recognized in females.

Recent studies demonstrate increased brain N-methyl-D-aspartate (NMDA) receptors in stages 2 and 3 of the disease. This age-specific increase in glutamate levels and their receptors contribute to brain damage. This first study will examine the effectiveness of dextromethorphan, an NMDA receptor antagonist, to ameliorate symptoms. Participants will be randomized to receive one of three doses of dextromethorphan. All participants will be admitted to the hospital for three days at the beginning of the study. During the hospitalization, participants will undergo physical exam, Dexascan, MRI, EEG, behavioral assessment, laboratory testing, and neuropsychological evaluations. Six months after baseline assessment, participants will be rehospitalized for 3 days for similar assessments.

Reduction in choline acetyltransferase activity in RTT patients may also contribute to disturbed cortical development and psychomotor retardation in RTT. Therefore, the second part of the study will evaluate the effect of donepezil hydrochloride, an inhibitor of acetylcholine-esterase, on acetylcholine levels. This portion of the study will not begin until pharmacokinetic data for donepezil in children is available.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Rett Syndrome
  • Drug: dextromethorphan
  • Drug: donepezil hydrochloride
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
90
June 2008
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Inclusion Criteria

  • Diagnosis of Rett syndrome
  • Mutation in MeCP2 gene
  • Typical EEG abnormalities (disorganized background, frontal central spikes, rhythmic theta)

Exclusion Criteria

  • Features of Rett syndrome with absence of MeCP2 mutation
  • Non-specific EEG changes
Both
1 Year to 15 Years
No
Contact: SakkuBai R. Naidu, MD 443-923-2778
Contact: Barbara Ann Bradford 443-923-2778 bradford@kennedykrieger.org
United States
 
NCT00069550
HD024448, 5 PO1 HD024448
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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Principal Investigator: SakkuBai R. Naidu, MD Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
December 2004

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP