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Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome

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ClinicalTrials.gov Identifier: NCT00069550
Recruitment Status : Unknown
Verified December 2004 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Recruitment status was:  Recruiting
First Posted : September 30, 2003
Last Update Posted : June 24, 2005
Sponsor:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Tracking Information
First Submitted Date  ICMJE September 29, 2003
First Posted Date  ICMJE September 30, 2003
Last Update Posted Date June 24, 2005
Study Start Date  ICMJE September 2004
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome
Official Title  ICMJE Pathogenesis of Rett Syndrome: Natural History and Treatment
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rett Syndrome
Intervention  ICMJE
  • Drug: dextromethorphan
  • Drug: donepezil hydrochloride
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
90
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE June 2008
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 15 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00069550
Other Study ID Numbers  ICMJE HD024448
5P01HD024448 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: SakkuBai R. Naidu, MD Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
PRS Account Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Verification Date December 2004

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