Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
Condition: Rett Syndrome
MeSH terms: Rett Syndrome; Syndrome
Intervention: dextromethorphan; placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Dextromethorphan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 57.0
Sex: All
Minimum age: 1 Year
Maximum age: 10 Years
Healthy volunteers: No
Keywords: Rett syndrome; RTT; MECP2; dextromethorphan; DM

Summary:

      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-00PD

      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.
    

Eligibility criteria:

        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.