Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. 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
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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.

Condition or disease Intervention/treatment Phase
Rett Syndrome Drug: dextromethorphan Drug: donepezil hydrochloride Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pathogenesis of Rett Syndrome: Natural History and Treatment
Study Start Date : September 2004
Estimated Study Completion Date : June 2008

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00069550

Contact: SakkuBai R. Naidu, MD 443-923-2778
Contact: Barbara Ann Bradford 443-923-2778

United States, Maryland
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States
Contact: SakkuBai R. Naidu, MD    443-923-2778      
Contact: Genila Bibat, MD    443-923-2778   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: SakkuBai R. Naidu, MD Hugo W. Moser Research Institute at Kennedy Krieger, Inc. Identifier: NCT00069550     History of Changes
Other Study ID Numbers: HD024448
5P01HD024448 ( U.S. NIH Grant/Contract )
First Posted: September 30, 2003    Key Record Dates
Last Update Posted: June 24, 2005
Last Verified: December 2004

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Glutamate/NMDA receptors
Cholinergic upregulation
Donepezil hydrochloride

Additional relevant MeSH terms:
Rett Syndrome
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Antitussive Agents
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents