Trial of Dextromethorphan in Rett Syndrome

NCT00593957 | Terminated Phase 2 Results DMC

• 1 other identifier: FD2408
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Rett Syndrome

Keywords

Rett Syndrome; Dextromethorphan

Outcome Measures

Primary Outcomes (1)

• Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.

  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 Outcomes (3)

• Improvement in Receptive Language as Measured by the Mullen Scale.

  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.

  Initial and 6 month followup

• Mean SSI Score for Total Subjects at Baseline and 6 Months

  0-6 months

Study Arms (3)

DM1( 0.25 mg/kg /day)

EXPERIMENTAL

Dextromethorphan 0.25 mg/kg per day

Drug: Dextromethorphan

DM2 (2.5 mg/kg/day)

EXPERIMENTAL

Dextromethorphan 2.5 mg/kg/day

Drug: Dextromethorphan

DM3 (5mg/kg/day)

EXPERIMENTAL

Dextromethorphan 5mg/kg/day

Drug: Dextromethorphan

Interventions

Dextromethorphan 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.

Also known as: Delsym

DM1( 0.25 mg/kg /day); DM2 (2.5 mg/kg/day); DM3 (5mg/kg/day)

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: lead

Study Sites (1)

Kennedy Krieger Institute/Johns Hopkins Medical Institutions

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Rett Syndrome

Interventions

Dextromethorphan

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

The trial was terminated due to the FDA requiring a placebo controlled trial instead of the ongoing open label trial. As recruitment was delayed,the total number of participants was also less than anticipated.

Results Point of Contact

• Title: Dr Sakkubai Naidu Professor of Neurology and Pediatrics
• Organization: Kennedy Krieger Institute

naidu@kennedykrieger.org

443-923-2778

Study Officials

• SakkuBai Naidu, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology and Pediatrics

Study Record Dates

• First Submitted: January 4, 2008
• First Posted: January 15, 2008
• Study Start: August 1, 2004
• Primary Completion: April 1, 2010
• Study Completion: June 1, 2010
• Last Updated: April 23, 2014
• Results First Posted: April 23, 2014

Record last verified: 2013-07

Locations

US (1)