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Placebo Controlled Trial of Dextromethorphan in Rett Syndrome (PCTDMRTT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Sponsor:
Information provided by (Responsible Party):
SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier:
NCT01520363
First received: January 25, 2012
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

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 OOPD and the Johns Hopkins Institute for Clinical and Translational Research (ICTR).

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.


Condition Intervention Phase
Rett Syndrome
Drug: dextromethorphan
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Placebo Controlled Trial of Dextromethorphan in Rett Syndrome

Resource links provided by NLM:


Further study details as provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Primary Outcome Measures:
  • Neuropsychological test (Mullen Scales of Early Learning). [ Time Frame: Initial evaluation and at the end of the 3 month trial ] [ Designated as safety issue: No ]
    The Neuropsychologist will assess cognitive status using the Mullen Scales of Early Learning (MULLEN), which will take approximately 2 - 2 1/2 hours during each of the two time points.


Secondary Outcome Measures:
  • Behavior scale: Vineland Adaptive Behavior Scales (VABS) [ Time Frame: Initial evaluation and at the end of the 3 month trial will take 45 minutes per evaluation ] [ Designated as safety issue: No ]
    Vineland Adaptive Behavior Scales (VABS)will be performed by the Neuropsychologist.

  • Behavior and temperament dysregulation measured by the Ghuman-Folstein Screen for Social Interaction (SSI);. [ Time Frame: Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes ] [ Designated as safety issue: No ]
    Behavior and temperament dysregulation.


Estimated Enrollment: 60
Study Start Date: March 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Study drug-dextromethorphan (DM)
MECP2 mutation positive subjects randomized to receive DM
Drug: 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.
Other Name: Delsym
Placebo Comparator: Placebo group
MECP2 positive subjects randomized to the placebo compound
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.
Other Name: Placebo

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

Ages Eligible for Study:   1 Year to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520363

Contacts
Contact: BarbaraAnn Bradford 443-923-2778 bradford@kennedykrieger.org
Contact: Marybeth Yablonski, RN, MS 443-923-2778 yablonski@kennedykrieger.org

Locations
United States, Maryland
The Johns Hopkins Institute for Clinical and Translational Research Recruiting
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Investigators
Principal Investigator: Sakkubai R Naidu, MD The Kennedy Krieger Institute and Johns Hopkins SOM
  More Information

No publications provided

Responsible Party: SakkuBai Naidu, M.D., Professor of Neurology and Pediatrics, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier: NCT01520363     History of Changes
Other Study ID Numbers: FD-004247-01
Study First Received: January 25, 2012
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:
Rett syndrome
RTT
MECP2
dextromethorphan
DM

Additional relevant MeSH terms:
Rett Syndrome
Syndrome
Disease
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Mental Retardation, X-Linked
Nervous System Diseases
Neurobehavioral Manifestations
Neurodegenerative Diseases
Neurologic Manifestations
Pathologic Processes
Dextromethorphan
Antitussive Agents
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014