Trial of Dextromethorphan in Rett Syndrome

NCT ID: NCT00593957

Last Updated: 2014-04-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2010-06-30

Brief Summary

Increased brain glutamate and its N-methyl-D-aspartate (NMDA) receptors found in the brain of younger Rett syndrome (RTT) patients cause toxic damage to neurons (the brain's nerve cells), and contributing to EEG spikes. Dextromethorphan (DM) acts by blocking NMDA/glutamate receptors. This study is being done to determine if DM will prevent the harmful over-stimulation of the neurons thereby reducing EEG spike activity. Treatment with DM consists of one of 3 different doses (0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day), and aims to find out which dose if any will help improve EEG abnormalities, behavior, cognition, and reduce seizures, as well as improve breathing abnormalities, motor capabilities, bone density, and GI dysfunction.

The study will include 90 females and males with RTT, 2 years-14.99 years of age, with a mutation in the methyl CpG binding protein 2 (MECP2) gene, and spikes on EEG, with or without clinical seizures.

Detailed Description

Patients meeting eligibility criteria(mutation +ve and having EEG spikes), will be admitted to the Pediatric Clinical Research Unit at Johns Hopkins Hospital and will have pharmacokinetics of DM determined to establish that they are rapid metabolizers of the drug. The baseline studies on initial admission include neurological, neuropsychology,EEG, gastroenterology, Occupational and Physical therapy evaluations. If the subject is a rapid metabolizer they will be randomized to one of the three drug doses. They are contacted by telephone, weekly in the first month, and monthly thereafter. They will be examined by a neurologist at 2 weeks,1 month, and 3 months during the drug trial. At each of these visits they will also be monitored for changes in complete blood count (CBC), electrolytes, and EKG. At the end of the 6 month drug trial the patients will be readmitted to Johns Hopkins Hospital when all baseline studies are repeated. Cost of travel, hospitalization and interim tests are free to participants.

Conditions

Rett Syndrome

Study Design

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

Study Groups

DM1( 0.25 mg/kg /day)

Dextromethorphan 0.25 mg/kg per day

Group Type: EXPERIMENTAL

Dextromethorphan

Intervention Type: DRUG

Subjects will be randomized to receive one of three dosage groups either 0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day of Dextromethorphan Polistirex (Delsym)oral syrup, which will be given exactly 12 hours apart in two divided doses during the 6 month trial.

Dextromethorphan

Intervention Type: DRUG

Dextromethorphan polistirex. Doses are 0.25 mg/kg/day, 2.5mg/kg/day, and 5 mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months.

DM2 (2.5 mg/kg/day)

Dextromethorphan 2.5 mg/kg/day

Group Type: EXPERIMENTAL

Dextromethorphan

Intervention Type: DRUG

Subjects will be randomized to receive one of three dosage groups either 0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day of Dextromethorphan Polistirex (Delsym)oral syrup, which will be given exactly 12 hours apart in two divided doses during the 6 month trial.

Dextromethorphan

Intervention Type: DRUG

Dextromethorphan polistirex. Doses are 0.25 mg/kg/day, 2.5mg/kg/day, and 5 mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months.

DM3 (5mg/kg/day)

Dextromethorphan 5mg/kg/day

Group Type: EXPERIMENTAL

Dextromethorphan

Intervention Type: DRUG

Subjects will be randomized to receive one of three dosage groups either 0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day of Dextromethorphan Polistirex (Delsym)oral syrup, which will be given exactly 12 hours apart in two divided doses during the 6 month trial.

Dextromethorphan

Intervention Type: DRUG

Dextromethorphan polistirex. Doses are 0.25 mg/kg/day, 2.5mg/kg/day, and 5 mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months.

Interventions

Dextromethorphan

Subjects will be randomized to receive one of three dosage groups either 0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day of Dextromethorphan Polistirex (Delsym)oral syrup, which will be given exactly 12 hours apart in two divided doses during the 6 month trial.

Intervention Type: DRUG

Dextromethorphan

Dextromethorphan polistirex. Doses are 0.25 mg/kg/day, 2.5mg/kg/day, and 5 mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months.

Intervention Type: DRUG

Other Intervention Names

Delsym; Delsym

Eligibility Criteria

Inclusion Criteria

1. those who have classic or atypical RTT with a proven mutation in the MeCP2 gene;

2. those with documented EEG evidence of spike activity who may or may not have clinical seizures;

3. subjects must be between 2years -14.99 years of age.

Exclusion Criteria

1. those without an established mutation in the MeCP2 gene;

2. those who do not have EEG evidence of spike activity;

3. those with mutations in the MeCP2 gene but who have had brain resection or surgical intervention; for example, tumor, hydrocephalus, severe head trauma; or, an associated severe medical illnesses such as vasculopathies, malignancies, diabetes, thyroid dysfunction, etc;

4. those on medications that could interact with DM, e.g. monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitor (SSRI), sibutramine etc. to avoid a serotonin syndrome; quinidine and drugs metabolized by the Cytochrome P450 (CYP450) isoform cytochrome P450 2D6 (CYP2D6) (e.g. amiodarone, haloperidol, propafenone, thioridazine);

5. those proven to be intermediate or slow metabolizers of DM;

6. those with reported adverse reactions to DM;

7. those whose pregnancy test is positive; and,

8. those showing poor compliance with any aspect of the study;

9. foster children

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

SakkuBai Naidu, M.D.

Professor of Neurology and Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

SakkuBai Naidu, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Kennedy Krieger Institute/Johns Hopkins Medical Institutions

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

FD2408

Identifier Type: -

Identifier Source: org_study_id