Rett SyndromePhase 2NCT00593957
Trial of Dextromethorphan in Rett Syndrome
A Phase 2 study testing Dextromethorphan in people with Rett Syndrome, run by Hugo W. Moser Research Institute at Kennedy Krieger, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 15 years
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- Dextromethorphan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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;
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- those whose pregnancy test is positive; and,
- those showing poor compliance with any aspect of the study;
- foster children
Trial locations and contacts
1 site in 1 country.
United States1 site
Kennedy Krieger Institute/Johns Hopkins Medical Institutions
Baltimore, Maryland, 21205
About this study
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.
Read the 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.
- Conditions
- Rett Syndrome
- Being tested
- Dextromethorphan
- Keywords
- Rett Syndrome, Dextromethorphan
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DextromethorphanDrug
Also called Delsym
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.
DextromethorphanDrug
Also called Delsym
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.
| Study group | Role | What they receive |
|---|---|---|
| DM1( 0.25 mg/kg /day) | Experimental | Dextromethorphan 0.25 mg/kg per day Receives: Drug: Dextromethorphan |
| DM2 (2.5 mg/kg/day) | Experimental | Dextromethorphan 2.5 mg/kg/day Receives: Drug: Dextromethorphan |
| DM3 (5mg/kg/day) | Experimental | Dextromethorphan 5mg/kg/day Receives: Drug: Dextromethorphan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Initial and 6-month post-treatment
Secondary outcomes (3)
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.
Measured: Change in mean between Initial and 6-month follow-up
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.
Measured: Initial and 6 month followup
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).
Measured: 0-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2008 (estimated)
- Study startAug 2004
- Primary completionApr 2010
- Study completionJun 2010
Why it stopped: Study changed to a placebo controlled trial of dextromethorphan
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
- Investigators
- SakkuBai Naidu, MD, Principal investigator, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00593957
- Sponsor's protocol ID
- FD2408
- Status last verified
- Jul 2013
- First submitted
- 4 Jan 2008
- Last updated
- 23 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Dextromethorphan in Rett Syndrome
- ClinicalTrials.gov ID
- NCT00593957
- Acronym / sponsor ID
- FD2408
- Conditions
- Rett Syndrome
- Keywords
- Rett Syndrome, Dextromethorphan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study changed to a placebo controlled trial of dextromethorphan
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Hugo W. Moser Research Institute at Kennedy Krieger, Inc.University, hospital or other
- Study start
- Aug 2004
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 15 Jan 2008 (estimated)
- Results
- Posted 23 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DM1( 0.25 mg/kg /day) | Experimental | Drug: DextromethorphanDextromethorphan 0.25 mg/kg per day |
| DM2 (2.5 mg/kg/day) | Experimental | Drug: DextromethorphanDextromethorphan 2.5 mg/kg/day |
| DM3 (5mg/kg/day) | Experimental | Drug: DextromethorphanDextromethorphan 5mg/kg/day |
Who may qualify
- Ages
- 2 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DextromethorphanAlso: DelsymSubjects 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. | Drug | DM1( 0.25 mg/kg /day), DM2 (2.5 mg/kg/day), DM3 (5mg/kg/day) |
| DextromethorphanAlso: DelsymDextromethorphan 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. | Drug | DM1( 0.25 mg/kg /day), DM2 (2.5 mg/kg/day), DM3 (5mg/kg/day) |
Primary outcome
Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.
Time frame: Initial and 6-month post-treatment
Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.
3 secondary outcomes
Improvement in Receptive Language as Measured by the Mullen Scale.
Time frame: Change in mean between Initial and 6-month follow-up
Difference in SSI Mean Score at Six Months Compared to Baseline for Each Treatment Arm.
Time frame: Initial and 6 month followup
Mean SSI Score for Total Subjects at Baseline and 6 Months
Time frame: 0-6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
SakkuBai Naidu, MD principal investigator
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dextromethorphan in people with Rett Syndrome, run by Hugo W. Moser Research Institute at Kennedy Krieger, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm. (time frame: Initial and 6-month post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2014.