Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome

NCT ID: NCT00069550

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2008-06-30

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.

Conditions

Rett Syndrome

Keywords

Glutamate/NMDA receptors; Cholinergic upregulation; Dextromethorphan; Donepezil hydrochloride; Aricept

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

dextromethorphan

Intervention Type: DRUG

donepezil hydrochloride

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: lead

Principal Investigators

SakkuBai R. Naidu, MD

Role: PRINCIPAL_INVESTIGATOR

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Locations

Kennedy Krieger Institute

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

SakkuBai R. Naidu, MD

Role: CONTACT

Phone: 443-923-2778

Barbara Ann Bradford

Role: CONTACT

Phone: 443-923-2778

Email: bradford@kennedykrieger.org

Facility Contacts

SakkuBai R. Naidu, MD

Role: primary

Genila Bibat, MD

Role: backup

Other Identifiers

5P01HD024448

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HD024448

Identifier Type: -

Identifier Source: org_study_id