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
  Purpose

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 Intervention Phase
Rett Syndrome
Drug: dextromethorphan
Drug: donepezil hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pathogenesis of Rett Syndrome: Natural History and Treatment

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Estimated Enrollment: 90
Study Start Date: September 2004
Estimated Study Completion Date: June 2008
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.

  Eligibility

Ages Eligible for Study:   1 Year to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00069550

Contacts
Contact: SakkuBai R. Naidu, MD 443-923-2778
Contact: Barbara Ann Bradford 443-923-2778 bradford@kennedykrieger.org

Locations
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    bibat@kennedykrieger.org   
Sponsors and Collaborators
Investigators
Principal Investigator: SakkuBai R. Naidu, MD Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00069550     History of Changes
Other Study ID Numbers: HD024448, 5 PO1 HD024448
Study First Received: September 29, 2003
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on August 21, 2014