Trial of Dextromethorphan in Rett Syndrome
Condition: Rett Syndrome
MeSH terms: Rett Syndrome; Syndrome
Intervention: Dextromethorphan; Dextromethorphan
Intervention description: 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.; 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.
Intervention MeSH terms: Dextromethorphan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 2 Years
Maximum age: 15 Years
Healthy volunteers: No
Keywords: Rett Syndrome; Dextromethorphan

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.
    

Eligibility criteria:

        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