Placebo Controlled Trial of Dextromethorphan in Rett Syndrome

NCT01520363 | Completed Phase 2 Results DMC

• 1 other identifier: FD-004247-01
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Rett Syndrome

Keywords

Rett syndrome; RTT; MECP2; dextromethorphan; DM

Outcome Measures

Primary Outcomes (4)

• Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention

  The Mullen Scales of Early Learning (MULLEN) Visual reception subscale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

  Initial evaluation and at the end of the 3 month trial

• Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention

  The Mullen Scales of Early Learning (MULLEN) Fine motor scale raw scores range from Minimum=0 to Maximum=49. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

  Baseline and 3 months

• Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention

  The Mullen Scales of Early Learning (MULLEN) Receptive Language scale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

  Baseline and 3 months

• Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention

  The Mullen Scales of Early Learning (MULLEN) Expressive Language scale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

  Baseline and 3 months

Secondary Outcomes (6)

• Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention

  Baseline evaluation and at the end of the 3 month study

• Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention

  Baseline and at the end of the 3 month trial

• Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention

  Baseline and at the end of the 3 month trial

• Change in VABS:Communication Domain Scores, Pre- and Post-Intervention

  Baseline and at the end of the 3 month trial

• Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention.

  Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes

Other Outcomes (7)

• Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention

  Baseline evaluation and at the end of the 3 month study

• Change in PedsQL Total Score, Pre- and Post-Intervention

  Baseline evaluation and at the end of the 3 month study

• Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention

  Baseline and at the end of the 3 month trial

Study Arms (2)

Study drug-dextromethorphan (DM)

ACTIVE COMPARATOR

MECP2 mutation positive subjects randomized to receive DM

Drug: dextromethorphan

Placebo group

PLACEBO COMPARATOR

MECP2 positive subjects randomized to the placebo compound

Drug: placebo

Interventions

dextromethorphan 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.

Also known as: Delsym

Study drug-dextromethorphan (DM)

placebo 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.

Placebo group

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: lead
• The Johns Hopkins Institute for Clinical and Translational Research (ICTR): collaborator

Study Sites (1)

The Johns Hopkins Institute for Clinical and Translational Research

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Rett Syndrome

Interventions

Dextromethorphan

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Sakkubai Naidu
• Organization: Hugo W. Moser Research Institute at Kennedy Krieger , Inc.

naidu@kennedykrieger.org

443 923 2778

Study Officials

• Sakkubai R Naidu, MD

  The Kennedy Krieger Institute and Johns Hopkins SOM

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology and Pediatrics

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: January 27, 2012
• Study Start: March 1, 2012
• Primary Completion: October 26, 2016
• Study Completion: October 26, 2016
• Last Updated: December 4, 2018
• Results First Posted: October 23, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)