Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Placebo Controlled Trial of Dextromethorphan in Rett Syndrome (PCTDMRTT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01520363
Recruitment Status : Completed
First Posted : January 27, 2012
Results First Posted : October 23, 2018
Last Update Posted : December 4, 2018
Sponsor:
Collaborator:
The Johns Hopkins Institute for Clinical and Translational Research (ICTR)
Information provided by (Responsible Party):
SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Tracking Information
First Submitted Date  ICMJE January 25, 2012
First Posted Date  ICMJE January 27, 2012
Results First Submitted Date  ICMJE July 31, 2018
Results First Posted Date  ICMJE October 23, 2018
Last Update Posted Date December 4, 2018
Actual Study Start Date  ICMJE March 2012
Actual Primary Completion Date October 26, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention [ Time Frame: Initial evaluation and at the end of the 3 month trial ]
    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.
  • Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention [ Time Frame: Baseline and 3 months ]
    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.
  • Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention [ Time Frame: Baseline and 3 months ]
    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.
  • Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention [ Time Frame: Baseline and 3 months ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
Neuropsychological test (Mullen Scales of Early Learning). [ Time Frame: Initial evaluation and at the end of the 3 month trial ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention [ Time Frame: Baseline evaluation and at the end of the 3 month study ]
    Vineland Adaptive Behavior Scales-II (VABS): Motor Skills Domain Scores individual items are scored on a Likert scale from 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. Motor Skills Domain raw scores range from: Minimum=0 to Maximum=100. A higher score is a better outcome.
  • Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention [ Time Frame: Baseline and at the end of the 3 month trial ]
    Vineland Adaptive Behavior Scales-II (VABS): Daily Living Skills Domain individual items are scored on a Likert scale from 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. The Daily Living Skills Domain measures personal behavior as well as domestic and community interaction skills. Daily Living Skills Domain raw scores range from Minimum=0 to Maximum=218.
  • Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention [ Time Frame: Baseline and at the end of the 3 month trial ]
    Vineland Adaptive Behavior Scales-II (VABS): Socialization Domain. Critical behaviors are scored on a Likert scale from 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. Socialization Domain raw scores range from: Minimum=0 to Maximum=152. A higher score is a better outcome.
  • Change in VABS:Communication Domain Scores, Pre- and Post-Intervention [ Time Frame: Baseline and at the end of the 3 month trial ]
    Vineland Adaptive Behavior Scales (VABS)-II Communication Domain Scores. The Communication Domain evaluates the receptive, expressive, and written communication skills of the child. Critical behaviors in each Subdomain item are rated as 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. Communication Domain raw scores range from: Minimum=0 to Maximum=198. A higher score is a better outcome.
  • Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention. [ Time Frame: Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes ]
    The Ghuman-Folstein Screen for Social Interaction (SSI) assesses the change in behavior and temperament dysregulation as a total score. The score ranges from 0-162, with 0 being most Impaired /has the strongest autism features and 162 having no impairment/no autism features.
  • Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention [ Time Frame: Initial evaluation and at the end of the 3 month study ]
    The Rett Syndrome Behavior Questionnaire (RSBQ) total score was assessed. The total score ranges from 0 to 90, with 0 exhibiting no Rett syndrome related symptoms and 90 showing the greatest amount of symptoms (worse outcome).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
Behavior scales: a) Vineland Adaptive Behavior Scales (VABS); b) 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 trial ]
Vineland Adaptive Behavior Scales (VABS), will be performed by the Neuropsychologist. Neurobehavioral evaluation will be performed by a child psychiatrist to assess behavioral abnormalities. Parents will complete the behavioral checklists/questionnaires including VABS and the Ghuman-Folstein Screen for Social Interaction (SSI),which would take approximately 1.5 hours during each of the two time points.
Current Other Pre-specified Outcome Measures
 (submitted: November 7, 2018)
  • Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention [ Time Frame: Baseline evaluation and at the end of the 3 month study ]
    Pediatric Quality of Life Inventory (PedsQL version 4). School Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).
  • Change in PedsQL Total Score, Pre- and Post-Intervention [ Time Frame: Baseline evaluation and at the end of the 3 month study ]
    Pediatric Quality of Life Inventory (PedsQL version 4) total score. Each item is rated on a 5-point Likert scale from 0 (Never) to 4 (Almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. The Total Score is the sum of all the items over the number of items answered on all the Scales. Higher scores indicate better HRQOL.
  • Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention [ Time Frame: Baseline and at the end of the 3 month trial ]
    Pediatric Quality of Life Inventory (PedsQL version 4). Social Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).
  • Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention [ Time Frame: Baseline evaluation and at the end of the 3 month study ]
    Pediatric Quality of Life Inventory (PedsQL version 4). Emotional Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).
  • Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention [ Time Frame: Initial evaluation and at the end of the 3 month study ]
    Pediatric Quality of Life Inventory (PedsQL version 4). Physical Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).
  • Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group [ Time Frame: Baseline evaluation and at the end of the 3 month study ]
    Change in Frequency of seizure count baseline to follow-up for children aged 0-4 years
  • Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group [ Time Frame: Baseline evaluation and at the end of the 3 month study ]
    Change in Frequency of seizures baseline to follow-up for children aged 5-10 years
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
Official Title  ICMJE Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rett Syndrome
Intervention  ICMJE
  • 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
  • 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.
Study Arms  ICMJE
  • Active Comparator: Study drug-dextromethorphan (DM)
    MECP2 mutation positive subjects randomized to receive DM
    Intervention: Drug: dextromethorphan
  • Placebo Comparator: Placebo group
    MECP2 positive subjects randomized to the placebo compound
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 25, 2018)
57
Original Estimated Enrollment  ICMJE
 (submitted: January 26, 2012)
60
Actual Study Completion Date  ICMJE October 26, 2016
Actual Primary Completion Date October 26, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 10 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01520363
Other Study ID Numbers  ICMJE FD-004247-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Study Sponsor  ICMJE Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Collaborators  ICMJE The Johns Hopkins Institute for Clinical and Translational Research (ICTR)
Investigators  ICMJE
Principal Investigator: Sakkubai R Naidu, MD The Kennedy Krieger Institute and Johns Hopkins SOM
PRS Account Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP