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Trial of Dextromethorphan in Rett Syndrome

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ClinicalTrials.gov Identifier: NCT00593957
Recruitment Status : Terminated (Study changed to a placebo controlled trial of dextromethorphan)
First Posted : January 15, 2008
Results First Posted : April 23, 2014
Last Update Posted : April 23, 2014
Sponsor:
Information provided by (Responsible Party):
SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Tracking Information
First Submitted Date  ICMJE January 4, 2008
First Posted Date  ICMJE January 15, 2008
Results First Submitted Date  ICMJE March 8, 2013
Results First Posted Date  ICMJE April 23, 2014
Last Update Posted Date April 23, 2014
Study Start Date  ICMJE August 2004
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
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 Measures  ICMJE
 (submitted: January 4, 2008)
Improvement in EEG abnormalities (spike counts) [ Time Frame: Initial and 6-month follow-up ]
Change History Complete list of historical versions of study NCT00593957 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
  • 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 Measures  ICMJE
 (submitted: January 4, 2008)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Dextromethorphan in Rett Syndrome
Official Title  ICMJE 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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rett Syndrome
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: DM1( 0.25 mg/kg /day)
    Dextromethorphan 0.25 mg/kg per day
    Interventions:
    • Drug: Dextromethorphan
    • Drug: Dextromethorphan
  • Experimental: DM2 (2.5 mg/kg/day)
    Dextromethorphan 2.5 mg/kg/day
    Interventions:
    • Drug: Dextromethorphan
    • Drug: Dextromethorphan
  • Experimental: DM3 (5mg/kg/day)
    Dextromethorphan 5mg/kg/day
    Interventions:
    • Drug: Dextromethorphan
    • Drug: Dextromethorphan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 26, 2014)
38
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2008)
90
Actual Study Completion Date  ICMJE June 2010
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 15 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00593957
Other Study ID Numbers  ICMJE FD2408
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Study Sponsor  ICMJE Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: SakkuBai Naidu, MD Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
PRS Account Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP