Placebo Controlled Trial of Dextromethorphan in Rett Syndrome (PCTDMRTT)
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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, that is sponsored by the FDA OOPD and 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 |
- 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.
- 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: | March 2015 |
| Estimated Primary Completion Date: | September 2014 (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, 2 years - 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: | 2 Years to 10 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- those who have classic or atypical RTT with a proven mutation in the MECP2 gene;
- subjects must be between 2 years - 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, propfenone, 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| Contact: BarbaraAnn Bradford | 443-923-2778 | bradford@kennedykrieger.org |
| Contact: Marybeth Yablonski, RN, MS | 443-923-2778 | yablonski@kennedykrieger.org |
| United States, Maryland | |
| The Johns Hopkins Institute for Clinical and Translational Research | Recruiting |
| Baltimore, Maryland, United States, 21287 | |
| 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: | December 3, 2012 |
| 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 Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Nervous System Diseases Mental Retardation, X-Linked Mental Retardation Neurobehavioral Manifestations Neurologic Manifestations Genetic Diseases, X-Linked Genetic Diseases, Inborn Dextromethorphan |
Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Antitussive Agents Central Nervous System Agents Therapeutic Uses Respiratory System Agents |
ClinicalTrials.gov processed this record on May 19, 2013