- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00593957
Trial of Dextromethorphan in Rett Syndrome
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21205
- Kennedy Krieger Institute/Johns Hopkins Medical Institutions
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- those who have classic or atypical RTT with a proven mutation in the MeCP2 gene;
- those with documented EEG evidence of spike activity who may or may not have clinical seizures;
- subjects must be between 2years -14.99 years of age.
Exclusion Criteria:
- those without an established mutation in the MeCP2 gene;
- those who do not have EEG evidence of spike activity;
- 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;
- 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);
- those proven to be intermediate or slow metabolizers of DM;
- those with reported adverse reactions to DM;
- those whose pregnancy test is positive; and,
- those showing poor compliance with any aspect of the study;
- foster children
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: DM1( 0.25 mg/kg /day)
Dextromethorphan 0.25 mg/kg per day
|
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.
Other Names:
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.
Other Names:
|
Experimental: DM2 (2.5 mg/kg/day)
Dextromethorphan 2.5 mg/kg/day
|
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.
Other Names:
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.
Other Names:
|
Experimental: DM3 (5mg/kg/day)
Dextromethorphan 5mg/kg/day
|
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.
Time Frame: Initial and 6-month post-treatment
|
Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.
|
Initial and 6-month post-treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Improvement in Receptive Language as Measured by the Mullen Scale.
Time Frame: Change in mean between Initial and 6-month follow-up
|
The Mullen Receptive language scale pre and 6 months post DM, measured as a change in the mean score of language, by age in months.
|
Change in mean between Initial and 6-month follow-up
|
Difference in SSI Mean Score at Six Months Compared to Baseline for Each Treatment Arm.
Time Frame: Initial and 6 month followup
|
The Screen for Social Interaction (SSI) is a 54-item parent/caregiver-report screening instrument that emphasizes reciprocal social interaction including joint attention skills.
The items are positive (prosocial) and are scored on a four-point frequency scale (child displays the behavior "almost never" = 0 to "almost all the time" = 3).
Thus lower scores reflect a slower or delayed development, and higher scores reflect more normative development.
SSI total scores range from 0-162.
There are no subscales.
Difference in Screen for Social Interaction (SSI) mean scores between baseline and 6 months post-treatment for each treatment arm are reported.
|
Initial and 6 month followup
|
Mean SSI Score for Total Subjects at Baseline and 6 Months
Time Frame: 0-6 months
|
Analysis of Difference in Mean Screen for Social Interaction (SSI) Score between 0-6 months for total sample (n=19).
|
0-6 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: SakkuBai Naidu, MD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Disease
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Mental Retardation, X-Linked
- Intellectual Disability
- Heredodegenerative Disorders, Nervous System
- Syndrome
- Rett Syndrome
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Respiratory System Agents
- Antitussive Agents
- Dextromethorphan
Other Study ID Numbers
- FD2408
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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