Rett Syndrome
Conditions
Keywords
Rett syndrome, RTT, MECP2, dextromethorphan, DM
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.
Interventions
DRUGdextromethorphan
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.
DRUGplacebo
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.
Sponsors
The Johns Hopkins Institute for Clinical and Translational Research (ICTR)
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 10 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention | 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, Expressive Language Sub-scale Scores, Pre- and Post-Intervention | 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. |
| Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention | 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; Fine Motor Sub-scale Scores, Pre- and Post-Intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention | 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: Motor Skills Domain Scores, Pre- and Post-Intervention | 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: Socialization Domain Scores, Pre- and Post-Intervention | 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 | 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. | 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 | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention | 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 Social Functioning Subscale Score, Pre- and Post-Intervention | 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 Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group | 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 | 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 |
| Change in PedsQL Total Score, Pre- and Post-Intervention | 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 School Functioning Subscale Score, Pre- and Post-Intervention | 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 Physical Functioning Subscale Score, Pre- and Post-Intervention | 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). |
Countries
United States
Participant flow
Pre-assignment details
A total of 57 participants were consented. Of these 5 were slow metabolizers who did not meet post consent eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| Study Drug-dextromethorphan (DM) MECP2 mutation positive subjects randomized to receive DM
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. | 26 |
| Placebo Group MECP2 positive subjects randomized to the placebo compound
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. | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Study Drug-dextromethorphan (DM) | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 26 Participants | 26 Participants | 52 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 4.75 years STANDARD_DEVIATION 2.52 | 4.91 years STANDARD_DEVIATION 1.91 | 4.83 years STANDARD_DEVIATION 2.22 |
| Region of Enrollment Canada | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Mexico | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 25 Participants | 25 Participants | 50 Participants |
| Sex: Female, Male Female | 26 Participants | 26 Participants | 52 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 | 0 / 24 | 0 / 26 |
| other Total, other adverse events | 0 / 26 | 0 / 26 | 18 / 24 | 22 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 0 / 24 | 0 / 26 |
Outcome results
Primary
Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention
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.
Time frame: Baseline and 3 months
Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention | 5.33 score on a scale | Standard Deviation 3.665 |
| Placebo Group | Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention | 6.73 score on a scale | Standard Deviation 3.8 |
| Study Drug Group at 3 Months | Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention | 6.76 score on a scale | Standard Deviation 5.504 |
| Placebo at 3 Months | Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention | 7.29 score on a scale | Standard Deviation 7.123 |
p-value: 0.0595% CI: [-2.886, 0.029]t-test, 2 sided
p-value: 0.95895% CI: [-1.589, 1.672]t-test, 2 sided
Primary
Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention
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.
Time frame: Baseline and 3 months
Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention | 5.38 score on a scale | Standard Deviation 5.5 |
| Placebo Group | Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention | 7.00 score on a scale | Standard Deviation 6.474 |
| Study Drug Group at 3 Months | Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention | 5.05 score on a scale | Standard Deviation 6.103 |
| Placebo at 3 Months | Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention | 7.04 score on a scale | Standard Deviation 6.564 |
p-value: 0.54195% CI: [-0.785, 1.451]t-test, 2 sided
p-value: 0.94695% CI: [-1.29, 1.206]t-test, 2 sided
Primary
Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention
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.
Time frame: Baseline and 3 months
Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention | 6.45 score on a scale | Standard Deviation 5.307 |
| Placebo Group | Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention | 6.95 score on a scale | Standard Deviation 5.269 |
| Study Drug Group at 3 Months | Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention | 6.68 score on a scale | Standard Deviation 5.472 |
| Placebo at 3 Months | Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention | 6.55 score on a scale | Standard Deviation 6.085 |
p-value: 0.73695% CI: [-1.609, 1.154]t-test, 2 sided
p-value: 0.58995% CI: [-1.143, 1.961]t-test, 2 sided
Primary
Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention
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.
Time frame: Initial evaluation and at the end of the 3 month trial
Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention | 5.45 score on a scale | Standard Deviation 3.419 |
| Placebo Group | Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention | 6.61 score on a scale | Standard Deviation 6.308 |
| Study Drug Group at 3 Months | Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention | 6.64 score on a scale | Standard Deviation 7.135 |
| Placebo at 3 Months | Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention | 6.57 score on a scale | Standard Deviation 5.008 |
p-value: 0.21195% CI: [-3.086, 0.722]t-test, 2 sided
p-value: 0.94995% CI: [-1.345, 1.432]t-test, 2 sided
Secondary
Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention.
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.
Time frame: Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention. | 73.1 units on a scale | Standard Deviation 22.86 |
| Placebo Group | Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention. | 71.3 units on a scale | Standard Deviation 17.26 |
| Study Drug Group at 3 Months | Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention. | 73.1 units on a scale | Standard Deviation 25.97 |
| Placebo at 3 Months | Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention. | 68.0 units on a scale | Standard Deviation 16.21 |
p-value: 0.4295% CI: [-11.8, 5.05]t-test, 2 sided
Secondary
Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention
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).
Time frame: Initial evaluation and at the end of the 3 month study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention | 33.8 units on a scale | Standard Deviation 13.21 |
| Placebo Group | Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention | 33.3 units on a scale | Standard Deviation 12.26 |
| Study Drug Group at 3 Months | Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention | 33.8 units on a scale | Standard Deviation 13.21 |
| Placebo at 3 Months | Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention | 33.3 units on a scale | Standard Deviation 12.26 |
p-value: <0.7395% CI: [-7.02, 4.96]t-test, 2 sided
Secondary
Change in VABS:Communication Domain Scores, Pre- and Post-Intervention
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.
Time frame: Baseline and at the end of the 3 month trial
Population: 52 MECP2 Mutation positive participants who are fast metabolizers were enrolled at baseline. Two participants in the baseline DM group were noncompliant and removed from the study. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in VABS:Communication Domain Scores, Pre- and Post-Intervention | 18.05 score on a scale | Standard Deviation 4.146 |
| Placebo Group | Change in VABS:Communication Domain Scores, Pre- and Post-Intervention | 18.08 score on a scale | Standard Deviation 4.261 |
| Study Drug Group at 3 Months | Change in VABS:Communication Domain Scores, Pre- and Post-Intervention | 17.91 score on a scale | Standard Deviation 5.032 |
| Placebo at 3 Months | Change in VABS:Communication Domain Scores, Pre- and Post-Intervention | 17.96 score on a scale | Standard Deviation 4.835 |
p-value: 0.83695% CI: [-1.22, 1.493]t-test, 2 sided
p-value: 0.82695% CI: [-0.993, 1.233]t-test, 2 sided
Secondary
Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention
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.
Time frame: Baseline and at the end of the 3 month trial
Population: 52 MECP2 Mutation positive participants who are fast metabolizers were enrolled in the study. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention | 21.64 score on a scale | Standard Deviation 6.939 |
| Placebo Group | Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention | 21.00 score on a scale | Standard Deviation 5.307 |
| Study Drug Group at 3 Months | Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention | 20.95 score on a scale | Standard Deviation 6.388 |
| Placebo at 3 Months | Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention | 19.84 score on a scale | Standard Deviation 4.589 |
p-value: 0.18295% CI: [-0.346, 1.709]t-test, 2 sided
p-value: <0.00595% CI: [0.391, 1.929]t-test, 2 sided
Secondary
Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention
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.
Time frame: Baseline evaluation and at the end of the 3 month study
Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention | 9.86 score on a scale | Standard Deviation 3.821 |
| Placebo Group | Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention | 11.36 score on a scale | Standard Deviation 4.838 |
| Study Drug Group at 3 Months | Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention | 9.64 score on a scale | Standard Deviation 3.959 |
| Placebo at 3 Months | Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention | 11.12 score on a scale | Standard Deviation 4.755 |
p-value: 0.48895% CI: [-0.442, 0.897]t-test, 2 sided
p-value: 0.44295% CI: [-0.394, 0.874]t-test, 2 sided
Secondary
Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention
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.
Time frame: Baseline and at the end of the 3 month trial
Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention | 24.14 score on a scale | Standard Deviation 5.557 |
| Placebo Group | Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention | 22.96 score on a scale | Standard Deviation 4.954 |
| Study Drug Group at 3 Months | Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention | 24.05 score on a scale | Standard Deviation 6.514 |
| Placebo at 3 Months | Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention | 22.48 score on a scale | Standard Deviation 5.524 |
p-value: 0.995% CI: [-1.463, 1.644]t-test, 2 sided
p-value: 0.35695% CI: [-0.573, 1.533]t-test, 2 sided
Other Pre-specified
Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention
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).
Time frame: Baseline evaluation and at the end of the 3 month study
Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention | 72.37 score on a scale | Standard Deviation 17.979 |
| Placebo Group | Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention | 68.93 score on a scale | Standard Deviation 13.182 |
| Study Drug Group at 3 Months | Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention | 68.621 score on a scale | Standard Deviation 24.3816 |
| Placebo at 3 Months | Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention | 68.214 score on a scale | Standard Deviation 113.8129 |
p-value: 0.54995% CI: [-9.1269, 16.6217]t-test, 2 sided
p-value: 0.87495% CI: [-8.8174, 10.246]t-test, 2 sided
Other Pre-specified
Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention
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).
Time frame: Initial evaluation and at the end of the 3 month study
Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention | 42.717 score on a scale | Standard Deviation 30.3026 |
| Placebo Group | Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention | 48.973 score on a scale | Standard Deviation 29.5643 |
| Study Drug Group at 3 Months | Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention | 38.900 score on a scale | Standard Deviation 29.7848 |
| Placebo at 3 Months | Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention | 48.133 score on a scale | Standard Deviation 34.9777 |
p-value: 0.69395% CI: [-16.2046, 23.8379]t-test, 2 sided
p-value: 0.90995% CI: [-14.6102, 16.2902]t-test, 2 sided
Other Pre-specified
Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention
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).
Time frame: Baseline evaluation and at the end of the 3 month study
Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention | 64.231 score on a scale | Standard Deviation 23.3682 |
| Placebo Group | Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention | 49.583 score on a scale | Standard Deviation 20.3793 |
| Study Drug Group at 3 Months | Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention | 55.769 score on a scale | Standard Deviation 25.2782 |
| Placebo at 3 Months | Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention | 44.592 score on a scale | Standard Deviation 14.2084 |
p-value: 0.37195% CI: [-11.3603, 28.2834]t-test, 2 sided
p-value: 0.35895% CI: [-6.4553, 16.4387]t-test, 2 sided
Other Pre-specified
Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention
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).
Time frame: Baseline and at the end of the 3 month trial
Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention | 58.53 score on a scale | Standard Deviation 21.849 |
| Placebo Group | Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention | 54.64 score on a scale | Standard Deviation 18.341 |
| Study Drug Group at 3 Months | Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention | 46.76 score on a scale | Standard Deviation 16.002 |
| Placebo at 3 Months | Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention | 47.14 score on a scale | Standard Deviation 20.448 |
p-value: 0.08395% CI: [-1.745, 25.275]t-test, 2 sided
p-value: 0.07395% CI: [-0.802, 15.802]t-test, 2 sided
Other Pre-specified
Change in PedsQL Total Score, Pre- and Post-Intervention
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.
Time frame: Baseline evaluation and at the end of the 3 month study
Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in PedsQL Total Score, Pre- and Post-Intervention | 54.018 score on a scale | Standard Deviation 18.5915 |
| Placebo Group | Change in PedsQL Total Score, Pre- and Post-Intervention | 54.157 score on a scale | Standard Deviation 14.9519 |
| Study Drug Group at 3 Months | Change in PedsQL Total Score, Pre- and Post-Intervention | 50.9235 score on a scale | Standard Deviation 19.11019 |
| Placebo at 3 Months | Change in PedsQL Total Score, Pre- and Post-Intervention | 51.7286 score on a scale | Standard Deviation 18.83983 |
p-value: 0.60395% CI: [-9.27756, 15.4658]t-test, 2 sided
p-value: 0.43295% CI: [-4.04665, 8.9038]t-test, 2 sided
Other Pre-specified
Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group
Change in Frequency of seizure count baseline to follow-up for children aged 0-4 years
Time frame: Baseline evaluation and at the end of the 3 month study
Population: Children enrolled at baseline aged 0 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group | 3 seizure count | Standard Deviation 1.41 |
| Placebo Group | Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group | 3.2 seizure count | Standard Deviation 1.32 |
| Study Drug Group at 3 Months | Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group | 3.7 seizure count | Standard Deviation 0.9 |
| Placebo at 3 Months | Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group | 3.1 seizure count | Standard Deviation 1.45 |
p-value: 0.2195% CI: [-2.17, 0.52]t-test, 2 sided
Other Pre-specified
Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group
Change in Frequency of seizures baseline to follow-up for children aged 5-10 years
Time frame: Baseline evaluation and at the end of the 3 month study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug-dextromethorphan (DM) | Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group | 3.6 seizure count | Standard Deviation 1.19 |
| Placebo Group | Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group | 2.8 seizure count | Standard Deviation 1.47 |
| Study Drug Group at 3 Months | Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group | 3.36 seizure count | Standard Deviation 1.12 |
| Placebo at 3 Months | Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group | 3.37 seizure count | Standard Deviation 1.2 |
p-value: 0.2895% CI: [-0.66, 2.15]t-test, 2 sided