Clinical Trial: Trial of Dextromethorphan in Rett Syndrome

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Trial of Dextromethorphan in Rett Syndrome

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 Summary: 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.
Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Current Primary Outcome: 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.


Original Primary Outcome: Improvement in EEG abnormalities (spike counts) [ Time Frame: Initial and 6-month follow-up ]

Current Secondary Outcome:

  • 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.
  • 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.
  • 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).


Original Secondary Outcome: 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 ]

Information By: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Dates:
Date Received: January 4, 2008
Date Started: August 2004
Date Completion:
Last Updated: March 26, 2014
Last Verified: July 2013