Placebo Controlled Trial of Dextromethorphan in Rett Syndrome (PCTDMRTT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Sponsor:
Information provided by (Responsible Party):
SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier:
NCT01520363
First received: January 25, 2012
Last updated: May 29, 2014
Last verified: May 2014

January 25, 2012
May 29, 2014
March 2012
June 2015   (final data collection date for primary outcome measure)
Neuropsychological test (Mullen Scales of Early Learning). [ Time Frame: Initial evaluation and at the end of the 3 month trial ] [ Designated as safety issue: No ]
The Neuropsychologist will assess cognitive status using the Mullen Scales of Early Learning (MULLEN), which will take approximately 2 - 2 1/2 hours during each of the two time points.
Same as current
Complete list of historical versions of study NCT01520363 on ClinicalTrials.gov Archive Site
  • Behavior scale: Vineland Adaptive Behavior Scales (VABS) [ Time Frame: Initial evaluation and at the end of the 3 month trial will take 45 minutes per evaluation ] [ Designated as safety issue: No ]
    Vineland Adaptive Behavior Scales (VABS)will be performed by the Neuropsychologist.
  • Behavior and temperament dysregulation measured by the Ghuman-Folstein Screen for Social Interaction (SSI);. [ Time Frame: Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes ] [ Designated as safety issue: No ]
    Behavior and temperament dysregulation.
Behavior scales: a) Vineland Adaptive Behavior Scales (VABS); b) Behavior and temperament dysregulation, measured by the Ghuman-Folstein Screen for Social Interaction (SSI); [ Time Frame: Initial evaluation and at the end of the 3 month trial ] [ Designated as safety issue: No ]

Vineland Adaptive Behavior Scales (VABS), will be performed by the Neuropsychologist.

Neurobehavioral evaluation will be performed by a child psychiatrist to assess behavioral abnormalities. Parents will complete the behavioral checklists/questionnaires including VABS and the Ghuman-Folstein Screen for Social Interaction (SSI),which would take approximately 1.5 hours during each of the two time points.

Not Provided
Not Provided
 
Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
Placebo Controlled Trial of Dextromethorphan in Rett Syndrome

Dr. Sakkubai Naidu, Principal Investigator, is initiating a double blinded placebo controlled clinical drug trial using dextromethorphan (DM) in Rett Syndrome (RTT), at the Pediatric Clinical Research Unit (PCRU) of the Johns Hopkins Hospital/Kennedy Krieger Institute.

Funding Source- FDA OOPD and the Johns Hopkins Institute for Clinical and Translational Research (ICTR).

It has been shown that receptors for a certain brain chemical called glutamate, in particular the NMDA type, are increased in the brain of young RTT patients (<10 years of age). This chemical and its receptors, when in excess, cause harmful over-stimulation of nerve cells in the brain, contributing in part to the seizures, behavioral problems, and learning disabilities in RTT.

The investigators propose to initiate a specific treatment using DM to counter/block the effects of this brain chemical and its excessive receptors to improve the ill effects of increased glutamate/NMDA receptors, because of DM's identified ability to block NMDA receptors. DM is available for human consumption. Infants and children with respiratory infections and cough, as well as non-ketotic hyperglycinemia, are treated with DM, which has been well tolerated.

The study will last for 3 months and will be limited to MECP2 mutation-positive children, one year - 9.99 years of age. This clinical trial, which is a placebo-controlled study, will randomize patients to the drug or placebo to determine the benefits of DM vs placebo on cognition, behavior, or seizures if present.

Your child will stay twice in the Pediatric Clinical Research Unit (PCRU) at Johns Hopkins ICTR, for 3 days during each admission. The first hospital stay will be for 3 days, before she starts the DM or placebo. The follow-up 3-day hospital stay will be 3 months after she starts taking DM or placebo. There will also be two interim follow up evaluations at 2 weeks and 1 month after she starts taking the DM or placebo consisting of a neurological evaluation, EKG, and blood work, which can take place at your local doctor's office or at Johns Hopkins, and will be paid for by this study. Our research nurse or research associate will contact you at least weekly during the first month, and at least monthly thereafter until the end of the 3-month study.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Rett Syndrome
  • Drug: dextromethorphan
    The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.
    Other Name: Delsym
  • Drug: placebo
    The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.
    Other Name: Placebo
  • Active Comparator: Study drug-dextromethorphan (DM)
    MECP2 mutation positive subjects randomized to receive DM
    Intervention: Drug: dextromethorphan
  • Placebo Comparator: Placebo group
    MECP2 positive subjects randomized to the placebo compound
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
June 2015
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • males and females who have classic or atypical RTT with a proven mutation in the MECP2 gene;
  • subjects must be between one year - 10 years of age.

Exclusion Criteria:

  • those without an established mutation in the MECP2 gene;
  • 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;
  • those showing poor compliance with any aspect of the study;
  • foster children.
Both
1 Year to 10 Years
No
Contact: BarbaraAnn Bradford 443-923-2778 bradford@kennedykrieger.org
Contact: Marybeth Yablonski, RN, MS 443-923-2778 yablonski@kennedykrieger.org
United States
 
NCT01520363
FD-004247-01
Yes
SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Not Provided
Principal Investigator: Sakkubai R Naidu, MD The Kennedy Krieger Institute and Johns Hopkins SOM
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
May 2014

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