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Trial of Dextromethorphan in Rett Syndrome

Primary Purpose

Rett Syndrome

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Dextromethorphan

About this trial

This is an interventional treatment trial for Rett Syndrome focused on measuring Rett Syndrome, Dextromethorphan

Eligibility Criteria

2 Years - 15 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

those who have classic or atypical RTT with a proven mutation in the MeCP2 gene;
those with documented EEG evidence of spike activity who may or may not have clinical seizures;
subjects must be between 2years -14.99 years of age.

Exclusion Criteria:

those without an established mutation in the MeCP2 gene;
those who do not have EEG evidence of spike activity;
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. monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitor (SSRI), sibutramine etc. to avoid a serotonin syndrome; quinidine and drugs metabolized by the Cytochrome P450 (CYP450) isoform cytochrome P450 2D6 (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; and,
those showing poor compliance with any aspect of the study;
foster children

Sites / Locations

Kennedy Krieger Institute/Johns Hopkins Medical Institutions

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

DM1( 0.25 mg/kg /day)

DM2 (2.5 mg/kg/day)

DM3 (5mg/kg/day)

Arm Description

Dextromethorphan 0.25 mg/kg per day

Dextromethorphan 2.5 mg/kg/day

Dextromethorphan 5mg/kg/day

Outcomes

Primary Outcome Measures

Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.

Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.

Secondary Outcome Measures

Improvement in Receptive Language as Measured by the Mullen Scale.

The Mullen Receptive language scale pre and 6 months post DM, measured as a change in the mean score of language, by age in months.

Difference in SSI Mean Score at Six Months Compared to Baseline for Each Treatment Arm.

The Screen for Social Interaction (SSI) is a 54-item parent/caregiver-report screening instrument that emphasizes reciprocal social interaction including joint attention skills. The items are positive (prosocial) and are scored on a four-point frequency scale (child displays the behavior "almost never" = 0 to "almost all the time" = 3). Thus lower scores reflect a slower or delayed development, and higher scores reflect more normative development. SSI total scores range from 0-162. There are no subscales. Difference in Screen for Social Interaction (SSI) mean scores between baseline and 6 months post-treatment for each treatment arm are reported.

Mean SSI Score for Total Subjects at Baseline and 6 Months

Analysis of Difference in Mean Screen for Social Interaction (SSI) Score between 0-6 months for total sample (n=19).

Full Information

NCT ID

NCT00593957

First Posted

January 4, 2008

Last Updated

March 26, 2014

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT00593957

Brief Title

Trial of Dextromethorphan in Rett Syndrome

Official Title

Trial of Dextromethorphan in Rett Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

July 2013

Overall Recruitment Status

Terminated

Why Stopped

Study changed to a placebo controlled trial of dextromethorphan

Study Start Date

August 2004 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Increased brain glutamate and its N-methyl-D-aspartate (NMDA) receptors found in the brain of younger Rett syndrome (RTT) patients cause toxic damage to neurons (the brain's nerve cells), and contributing to EEG spikes. Dextromethorphan (DM) acts by blocking NMDA/glutamate receptors. This study is being done to determine if DM will prevent the harmful over-stimulation of the neurons thereby reducing EEG spike activity. Treatment with DM consists of one of 3 different doses (0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day), and aims to find out which dose if any will help improve EEG abnormalities, behavior, cognition, and reduce seizures, as well as improve breathing abnormalities, motor capabilities, bone density, and GI dysfunction. The study will include 90 females and males with RTT, 2 years-14.99 years of age, with a mutation in the methyl CpG binding protein 2 (MECP2) gene, and spikes on EEG, with or without clinical seizures.

Detailed Description

Patients meeting eligibility criteria(mutation +ve and having EEG spikes), will be admitted to the Pediatric Clinical Research Unit at Johns Hopkins Hospital and will have pharmacokinetics of DM determined to establish that they are rapid metabolizers of the drug. The baseline studies on initial admission include neurological, neuropsychology,EEG, gastroenterology, Occupational and Physical therapy evaluations. If the subject is a rapid metabolizer they will be randomized to one of the three drug doses. They are contacted by telephone, weekly in the first month, and monthly thereafter. They will be examined by a neurologist at 2 weeks,1 month, and 3 months during the drug trial. At each of these visits they will also be monitored for changes in complete blood count (CBC), electrolytes, and EKG. At the end of the 6 month drug trial the patients will be readmitted to Johns Hopkins Hospital when all baseline studies are repeated. Cost of travel, hospitalization and interim tests are free to participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rett Syndrome

Keywords

Rett Syndrome, Dextromethorphan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DM1( 0.25 mg/kg /day)

Arm Type

Experimental

Arm Description

Dextromethorphan 0.25 mg/kg per day

Arm Title

DM2 (2.5 mg/kg/day)

Arm Type

Experimental

Arm Description

Dextromethorphan 2.5 mg/kg/day

Arm Title

DM3 (5mg/kg/day)

Arm Type

Experimental

Arm Description

Dextromethorphan 5mg/kg/day

Intervention Type

Drug

Intervention Name(s)

Dextromethorphan

Other Intervention Name(s)

Delsym

Intervention Description

Subjects will be randomized to receive one of three dosage groups either 0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day of Dextromethorphan Polistirex (Delsym)oral syrup, which will be given exactly 12 hours apart in two divided doses during the 6 month trial.

Intervention Type

Drug

Intervention Name(s)

Dextromethorphan

Other Intervention Name(s)

Delsym

Intervention Description

Dextromethorphan polistirex. Doses are 0.25 mg/kg/day, 2.5mg/kg/day, and 5 mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months.

Primary Outcome Measure Information:

Title

Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.

Description

Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.

Time Frame

Initial and 6-month post-treatment

Secondary Outcome Measure Information:

Title

Improvement in Receptive Language as Measured by the Mullen Scale.

Description

The Mullen Receptive language scale pre and 6 months post DM, measured as a change in the mean score of language, by age in months.

Time Frame

Change in mean between Initial and 6-month follow-up

Title

Difference in SSI Mean Score at Six Months Compared to Baseline for Each Treatment Arm.

Description

Time Frame

Initial and 6 month followup

Title

Mean SSI Score for Total Subjects at Baseline and 6 Months

Description

Analysis of Difference in Mean Screen for Social Interaction (SSI) Score between 0-6 months for total sample (n=19).

Time Frame

0-6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: those who have classic or atypical RTT with a proven mutation in the MeCP2 gene; those with documented EEG evidence of spike activity who may or may not have clinical seizures; subjects must be between 2years -14.99 years of age. Exclusion Criteria: those without an established mutation in the MeCP2 gene; those who do not have EEG evidence of spike activity; 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. monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitor (SSRI), sibutramine etc. to avoid a serotonin syndrome; quinidine and drugs metabolized by the Cytochrome P450 (CYP450) isoform cytochrome P450 2D6 (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; and, those showing poor compliance with any aspect of the study; foster children

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

SakkuBai Naidu, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Kennedy Krieger Institute/Johns Hopkins Medical Institutions

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

12. IPD Sharing Statement

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Trial of Dextromethorphan in Rett Syndrome

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