Trial of Dextromethorphan in Rett Syndrome - Full Text View

Purpose

Increased brain glutamate and its 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 MECP2 gene, and spikes on EEG, with or without clinical seizures.

Condition	Intervention	Phase
Rett Syndrome	Drug: Dextromethorphan	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Trial of Dextromethorphan in Rett Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: MECP2 duplication syndrome PPM-X syndrome Renpenning syndrome Rett syndrome

MedlinePlus related topics: Rett Syndrome Seizures

Drug Information available for: Dextromethorphan hydrobromide Dextromethorphan

U.S. FDA Resources

Further study details as provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Primary Outcome Measures:

Reduction in EEG spike counts [ Time Frame: 6-months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Improvement in respiratory irregularities, gait/motor capabilities, osteopenia, cognition and temperament, GI dysfunction, as well as reduced seizure frequency. [ Time Frame: Initial and 6-month follow-up ] [ Designated as safety issue: No ]
Improved alertness and social interaction [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment:	35
Study Start Date:	August 2004
Study Completion Date:	June 2010
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: DM1( 0.25 mg/kg /day) Dextromethorphan 0.25 mg/kg per day	Drug: 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. Other Name: Delsym 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. Other Name: Delsym
Experimental: DM2 (2.5 mg/kg/day) Dextromethorphan 2.5 mg/kg/day	Drug: 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. Other Name: Delsym 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. Other Name: Delsym
Experimental: DM3 (5mg/kg/day) Dextromethorphan 5mg/kg/day	Drug: 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. Other Name: Delsym 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. Other Name: Delsym

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,gastroenterology, DEXAscan, Occupational and Physical therapy evaluations, Brain stem auditory evoked responses and MisMatch negativity testing,gait analysis,esophageal manometry and pH probe studies. 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 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.

Eligibility

Ages Eligible for Study:	2 Years to 15 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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. MAO inhibitors, SSRI, sibutramine etc. to avoid a serotonin syndrome; quinidine and drugs metabolized by the CYP450 isoform 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00593957

Locations

United States, Maryland
Kennedy Krieger Institute/Johns Hopkins Medical Institutions
Baltimore, Maryland, United States, 21205

Sponsors and Collaborators

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

Investigators

Principal Investigator:

SakkuBai Naidu, MD

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

More Information

No publications provided

Responsible Party:	SakkuBai Naidu, M.D., Professor of Neurology and Pediatrics, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier:	NCT00593957 History of Changes
Other Study ID Numbers:	FD2408
Study First Received:	January 4, 2008
Last Updated:	October 4, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Rett Syndrome
Dextromethorphan

Additional relevant MeSH terms:

Rett Syndrome
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Dextromethorphan

Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses
Respiratory System Agents

ClinicalTrials.gov processed this record on May 22, 2013