Clinical trial NCT01520363: Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
Official title: Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rett Syndrome
Keywords: Rett syndrome
RTT
MECP2
dextromethorphan
DM
Lead sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Sponsor class: OTHER
Collaborators: name: The Johns Hopkins Institute for Clinical and Translational Research (ICTR)
First posted: 2012-01-27
Enrollment: 57
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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.

Primary outcomes:
measure: Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention
timeFrame: Initial evaluation and at the end of the 3 month trial
measure: Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention
timeFrame: Baseline and 3 months
measure: Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention
timeFrame: Baseline and 3 months
measure: Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention
timeFrame: Baseline evaluation and at the end of the 3 month study
measure: Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention
timeFrame: Baseline and at the end of the 3 month trial
measure: Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention
timeFrame: Baseline and at the end of the 3 month trial
measure: Change in VABS:Communication Domain Scores, Pre- and Post-Intervention
timeFrame: Baseline and at the end of the 3 month trial
measure: Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention.
timeFrame: Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes
measure: Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention
timeFrame: Initial evaluation and at the end of the 3 month study
Other outcomes:
measure: Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention
timeFrame: Baseline evaluation and at the end of the 3 month study
measure: Change in PedsQL Total Score, Pre- and Post-Intervention
timeFrame: Baseline evaluation and at the end of the 3 month study
measure: Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention
timeFrame: Baseline and at the end of the 3 month trial
measure: Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention
timeFrame: Baseline evaluation and at the end of the 3 month study
measure: Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention
timeFrame: Initial evaluation and at the end of the 3 month study
measure: Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group
timeFrame: Baseline evaluation and at the end of the 3 month study
measure: Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group
timeFrame: Baseline evaluation and at the end of the 3 month study
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins Institute for Clinical and Translational Research
state: Maryland
Study officials:
affiliation: The Kennedy Krieger Institute and Johns Hopkins SOM
name: Sakkubai R Naidu, MD
role: PRINCIPAL_INVESTIGATOR
References: