Placebo Controlled Trial of Dextromethorphan in Rett Syndrome

NCT ID: NCT01520363

Last Updated: 2018-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2016-10-26

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.

Conditions

Rett Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Study drug-dextromethorphan (DM)

MECP2 mutation positive subjects randomized to receive DM

Group Type: ACTIVE_COMPARATOR

dextromethorphan

Intervention Type: DRUG

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.

Placebo group

MECP2 positive subjects randomized to the placebo compound

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Delsym

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Johns Hopkins Institute for Clinical and Translational Research (ICTR)

UNKNOWN

Sponsor Role: collaborator

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

OTHER

Sponsor Role: lead

Responsible Party

SakkuBai Naidu, M.D.

Professor of Neurology and Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sakkubai R Naidu, MD

Role: PRINCIPAL_INVESTIGATOR

The Kennedy Krieger Institute and Johns Hopkins SOM

Locations

The Johns Hopkins Institute for Clinical and Translational Research

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

FD-004247-01

Identifier Type: -

Identifier Source: org_study_id