PCTDMRTT: Placebo Controlled Trial of Dextromethorphan in Rett Syndrome

• Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01520363
• Collaborator: The Johns Hopkins Institute for Clinical and Translational Research (ICTR) (Other)
• Enrollment: 57
• Location: 1
• Arms: 2
• Actual Duration (Months): 55.9
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rett Syndrome	Drug: dextromethorphan; Drug: placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
• Actual Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Oct 26, 2016
• Actual Study Completion Date: Oct 26, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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 Outcome Measures

1. 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).

2. 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.

3. 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).

4. 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).

5. 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).

6. 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

7. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 10 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Johns Hopkins Institute for Clinical and Translational Research	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• The Johns Hopkins Institute for Clinical and Translational Research (ICTR)

Investigators

• Principal Investigator: Sakkubai R Naidu, MD, The Kennedy Krieger Institute and Johns Hopkins SOM

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 12, 2013

More Information

Publications

None 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
• Other Study ID Numbers: FD-004247-01
• First Posted: Jan 27, 2012
• Last Update Posted: Dec 4, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by SakkuBai Naidu, M.D., Professor of Neurology and Pediatrics, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: Rett syndrome; RTT; MECP2; dextromethorphan; DM
• Additional relevant MeSH terms: Rett Syndrome; Syndrome; Dextromethorphan

Study Results

Participant Flow

Pre-assignment Detail	A total of 57 participants were consented. Of these 5 were slow metabolizers who did not meet post consent eligibility criteria.

Arm/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	26	26
COMPLETED	24	26
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	26	26	52
Age (Count of Participants)
<=18 years	26 100%	26 100%	52 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.75 (2.52)	4.91 (1.91)	4.83 (2.22)
Sex: Female, Male (Count of Participants)
Female	26 100%	26 100%	52 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	25 96.2%	25 96.2%	50 96.2%
Canada	0 0%	1 3.8%	1 1.9%
Mexico	1 3.8%	0 0%	1 1.9%

Outcome Measures

1. Primary Outcome

Title	Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM at baseline 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.	MECP2 positive subjects randomized to the placebo at baseline 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.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	5.45 (3.419)	6.61 (6.308)	6.64 (7.135)	6.57 (5.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.211
	Comments
	Method	t-test, 2 sided
	Comments	df=21
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.182
	Confidence Interval	(2-Sided) 95%; -3.086 to .722
	Parameter Dispersion	Type: Standard Deviation; Value: 4.294
	Estimation Comments
Other Statistical Analysis		t= -1.291; p=.211

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.949
	Comments
	Method	t-test, 2 sided
	Comments	df=22
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	.043
	Confidence Interval	(2-Sided) 95%; -1.345 to 1.432
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .670
	Estimation Comments

2. Primary Outcome

Title	Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM at baseline 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.	MECP2 positive subjects randomized to the placebo at baseline 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.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	5.38 (5.5)	7.00 (6.474)	5.05 (6.103)	7.04 (6.564)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.541
	Comments	df=20
	Method	t-test, 2 sided
	Comments	df=20
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.333
	Confidence Interval	(2-Sided) 95%; -0.785 to 1.451
	Parameter Dispersion	Type: Standard Deviation; Value: 2.456
	Estimation Comments
Other Statistical Analysis		t=0.622; p=.541

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.946
	Comments	df=23
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-.042
	Confidence Interval	(2-Sided) 95%; -1.290 to 1.206
	Parameter Dispersion	Type: Standard Deviation; Value: 2.956
	Estimation Comments
Other Statistical Analysis		t=-.069; p=0.946

3. Primary Outcome

Title	Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM at baseline 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.	MECP2 positive subjects randomized to the placebo at baseline 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.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	6.45 (5.307)	6.95 (5.269)	6.68 (5.472)	6.55 (6.085)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.736
	Comments
	Method	t-test, 2 sided
	Comments	df=21
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.227
	Confidence Interval	(2-Sided) 95%; -1.609 to 1.154
	Parameter Dispersion	Type: Standard Deviation; Value: 3.116
	Estimation Comments
Other Statistical Analysis		t=-0.342; p=0.736

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.589
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.409
	Confidence Interval	(2-Sided) 95%; -1.143 to 1.961
	Parameter Dispersion	Type: Standard Deviation; Value: 3.500
	Estimation Comments
Other Statistical Analysis		t=0.548; p=0.589

4. Primary Outcome

Title	Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM at baseline 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.	MECP2 positive subjects randomized to the placebo at baseline 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.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	5.33 (3.665)	6.73 (3.8)	6.76 (5.504)	7.29 (7.123)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.05
	Comments
	Method	t-test, 2 sided
	Comments	df=20
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.429
	Confidence Interval	(2-Sided) 95%; -2.886 to 0.029
	Parameter Dispersion	Type: Standard Deviation; Value: 3.203
	Estimation Comments
Other Statistical Analysis		t=-2.044; p=0.05

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.958
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.042
	Confidence Interval	(2-Sided) 95%; -1.589 to 1.672
	Parameter Dispersion	Type: Standard Deviation; Value: 3.862
	Estimation Comments
Other Statistical Analysis		t=0.053; p=0.958

5. Secondary Outcome

Title	Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug-dextromethorphan (DM) at 3 Months	Placebo Group at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) at baseline: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study.	MECP2 positive subjects randomized to the placebo compound at baseline. 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.	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) who completed study assessments at the 3 month time point.	MECP2 positive subjects randomized to the placebo compound who completed the assessments at the 3 month time point.
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	9.86 (3.821)	11.36 (4.838)	9.64 (3.959)	11.12 (4.755)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.488
	Comments
	Method	t-test, 2 sided
	Comments	df=21
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	0.227
	Confidence Interval	(2-Sided) 95%; -0.442 to 0.897
	Parameter Dispersion	Type: Standard Deviation; Value: 1.510
	Estimation Comments
Other Statistical Analysis		t=0.706; p=0.488

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.442
	Comments
	Method	t-test, 2 sided
	Comments	df=24
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; -0.394 to 0.874
	Parameter Dispersion	Type: Standard Deviation; Value: 1.535
	Estimation Comments
Other Statistical Analysis		t=0.782; p=0.442

6. Secondary Outcome

Title	Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug-dextromethorphan (DM) at 3 Months	Placebo Group at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) at baseline: The DM group took 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study.	MECP2 positive subjects randomized to the placebo compound at baseline: The placebo was 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 dispensed the placebo to the participants.	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) who completed the study at 3 months	MECP2 positive subjects randomized to the placebo compound were still active in the study at 3 months.
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	21.64 (6.939)	21.00 (5.307)	20.95 (6.388)	19.84 (4.589)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.182
	Comments
	Method	t-test, 2 sided
	Comments	df=21
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.682
	Confidence Interval	(2-Sided) 95%; -0.346 to 1.709
	Parameter Dispersion	Type: Standard Deviation; Value: 2.317
	Estimation Comments
Other Statistical Analysis		t=1.380; p=0.182

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.005
	Comments
	Method	t-test, 2 sided
	Comments	df=24
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.160
	Confidence Interval	(2-Sided) 95%; 0.391 to 1.929
	Parameter Dispersion	Type: Standard Deviation; Value: 1.864
	Estimation Comments
Other Statistical Analysis		t=3.112; p=0.005

7. Secondary Outcome

Title	Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug-dextromethorphan (DM) at 3 Months	Placebo Group at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) at baseline: 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 dispensed the DM to the study participants.	MECP2 positive subjects randomized to the placebo compound at baseline: The placebo was 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 dispensed the placebo to the participants.	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) at 3 month time period.	MECP2 mutation positive subjects randomized to receive DM placebo at 3 month time period.
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	24.14 (5.557)	22.96 (4.954)	24.05 (6.514)	22.48 (5.524)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	.091
	Confidence Interval	(2-Sided) 95%; -1.463 to 1.644
	Parameter Dispersion	Type: Standard Deviation; Value: 3.504
	Estimation Comments
Other Statistical Analysis		t=0.122; p=0.90

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.356
	Comments
	Method	t-test, 2 sided
	Comments	df=24
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.480
	Confidence Interval	(2-Sided) 95%; -0.573 to 1.533
	Parameter Dispersion	Type: Standard Deviation; Value: 2.551
	Estimation Comments
Other Statistical Analysis		t=0.941; p=0.356

8. Secondary Outcome

Title	Change in VABS:Communication Domain Scores, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug-dextromethorphan (DM) at 3 Months	Placebo Group at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) at baseline: 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.	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.	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) and active in study at 3 month time point.	MECP2 mutation positive subjects randomized to receive Placebo and active in study at 3 month time point.
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	18.05 (4.146)	18.08 (4.261)	17.91 (5.032)	17.96 (4.835)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.836
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.136
	Confidence Interval	(2-Sided) 95%; -1.220 to 1.493
	Parameter Dispersion	Type: Standard Deviation; Value: 3.060
	Estimation Comments
Other Statistical Analysis		t=0.209; p=0.836

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.826
	Comments
	Method	t-test, 2 sided
	Comments	df=24
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.120
	Confidence Interval	(2-Sided) 95%; -0.993 to 1.233
	Parameter Dispersion	Type: Standard Deviation; Value: 2.698
	Estimation Comments
Other Statistical Analysis		t=0.222; p=0.826

9. Secondary Outcome

Title	Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM at baseline 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.	MECP2 positive subjects randomized to the placebo at baseline 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.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	22	24	22	24
Mean (Standard Deviation) [units on a scale]	73.1 (22.86)	71.3 (17.26)	73.1 (25.97)	68.0 (16.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Placebo Group, Study Drug Group at 3 Months, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.38
	Confidence Interval	(2-Sided) 95%; -11.80 to 5.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.18
	Estimation Comments

10. Secondary Outcome

Title	Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug-dextromethorphan (DM) at 3 Months	Placebo Group at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) at baseline: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study.	MECP2 positive subjects randomized to the placebo compound at baseline. 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.	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) who completed study assessments at the 3 month time point.	MECP2 positive subjects randomized to the placebo compound who completed the assessments at the 3 month time point.
Measure Participants	22	24	22	24
Mean (Standard Deviation) [units on a scale]	33.8 (13.21)	33.3 (12.26)	33.8 (13.21)	33.3 (12.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Placebo Group, Study Drug Group at 3 Months, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.73
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.03
	Confidence Interval	(2-Sided) 95%; -7.02 to 4.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.97
	Estimation Comments

11. Other Pre-specified Outcome

Title	Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive dextromethorphan(DM) at baseline	MECP2 positive subjects randomized to the placebo at baseline.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	64.231 (23.3682)	49.583 (20.3793)	55.769 (25.2782)	44.592 (14.2084)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.371
	Comments
	Method	t-test, 2 sided
	Comments	df=12
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.4615
	Confidence Interval	(2-Sided) 95%; -11.3603 to 28.2834
	Parameter Dispersion	Type: Standard Deviation; Value: 32.8016
	Estimation Comments
Other Statistical Analysis		t=0.903; p=0.371

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.358
	Comments
	Method	t-test, 2 sided
	Comments	df=11
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.9917
	Confidence Interval	(2-Sided) 95%; -6.4553 to 16.4387
	Parameter Dispersion	Type: Standard Deviation; Value: 18.0163
	Estimation Comments	t=0.960; p=0.358

12. Other Pre-specified Outcome

Title	Change in PedsQL Total Score, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive dextromethorphan(DM) at baseline	MECP2 positive subjects randomized to the placebo at baseline.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	54.018 (18.5915)	54.157 (14.9519)	50.9235 (19.11019)	51.7286 (18.83983)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.603
	Comments
	Method	t-test, 2 sided
	Comments	df=16
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.09412
	Confidence Interval	(2-Sided) 95%; -9.27756 to 15.46580
	Parameter Dispersion	Type: Standard Deviation; Value: 24.06228
	Estimation Comments	t=0.530; p=0.603

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.432
	Comments
	Method	t-test, 2 sided
	Comments	df=13
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.42857
	Confidence Interval	(2-Sided) 95%; -4.04665 to 8.90380
	Parameter Dispersion	Type: Standard Deviation; Value: 11.21479
	Estimation Comments	t=0.810; p=0.432

13. Other Pre-specified Outcome

Title	Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive dextromethorphan(DM) at baseline	MECP2 positive subjects randomized to the placebo at baseline.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	58.53 (21.849)	54.64 (18.341)	46.76 (16.002)	47.14 (20.448)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.083
	Comments
	Method	t-test, 2 sided
	Comments	df=16
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	11.765
	Confidence Interval	(2-Sided) 95%; -1.745 to 25.275
	Parameter Dispersion	Type: Standard Deviation; Value: 26.276
	Estimation Comments
Other Statistical Analysis		t=1.846; p=0.083

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.073
	Comments
	Method	t-test, 2 sided
	Comments	df=13
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	7.500
	Confidence Interval	(2-Sided) 95%; -0.802 to 15.802
	Parameter Dispersion	Type: Standard Deviation; Value: 14.378
	Estimation Comments
Other Statistical Analysis		t=1.952; p=0.073

14. Other Pre-specified Outcome

Title	Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug-dextromethorphan (DM) at 3 Months	Placebo Group at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) at baseline: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study.	MECP2 positive subjects randomized to the placebo compound at baseline. 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.	MECP2 mutation positive subjects randomized to receive DM (dextromethorphan) who completed study assessments at the 3 month time point.	MECP2 positive subjects randomized to the placebo compound who completed the assessments at the 3 month time point.
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	72.37 (17.979)	68.93 (13.182)	68.621 (24.3816)	68.214 (113.8129)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.549
	Comments
	Method	t-test, 2 sided
	Comments	df=18
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.7474
	Confidence Interval	(2-Sided) 95%; -9.1269 to 16.6217
	Parameter Dispersion	Type: Standard Deviation; Value: 26.7110
	Estimation Comments	t=0.612; p=0.549

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.874
	Comments
	Method	t-test, 2 sided
	Comments	df=13
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.7143
	Confidence Interval	(2-Sided) 95%; -8.8174 to 10.2460
	Parameter Dispersion	Type: Standard Deviation; Value: 16.5084
	Estimation Comments	t=0.162; p=0.874

15. Other Pre-specified Outcome

Title	Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive dextromethorphan(DM) at baseline	MECP2 positive subjects randomized to the placebo at baseline.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	24	26	22	25
Mean (Standard Deviation) [score on a scale]	42.717 (30.3026)	48.973 (29.5643)	38.900 (29.7848)	48.133 (34.9777)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Study Drug Group at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.693
	Comments
	Method	t-test, 2 sided
	Comments	df=17
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.8167
	Confidence Interval	(2-Sided) 95%; -16.2046 to 23.8379
	Parameter Dispersion	Type: Standard Deviation; Value: 40.2609
	Estimation Comments	t=0.402; p=0.693

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Group, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.909
	Comments
	Method	t-test, 2 sided
	Comments	df=14
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.8400
	Confidence Interval	(2-Sided) 95%; -14.6102 to 16.2902
	Parameter Dispersion	Type: Standard Deviation; Value: 27.8994
	Estimation Comments	t=0.117; p=0.909

16. Other Pre-specified Outcome

Title	Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group
Description	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

Outcome Measure Data

Analysis Population Description

Children enrolled at baseline aged 0 to 4 years

Arm/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug-dextromethorphan (DM) at 3 Months	Placebo Group at 3 Months
Arm/Group Description	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.	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.	MECP2 mutation positive subjects randomized to DM at 3 months.	MECP2 mutation positive subjects randomized to placebo at 3 months,
Measure Participants	11	10	11	10
Mean (Standard Deviation) [seizure count]	3 (1.41)	3.2 (1.32)	3.7 (.90)	3.1 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Placebo Group, Study Drug Group at 3 Months, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -2.17 to 0.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.64
	Estimation Comments

17. Other Pre-specified Outcome

Title	Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Drug-dextromethorphan (DM)	Placebo Group	Study Drug Group at 3 Months	Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive dextromethorphan(DM) at baseline	MECP2 positive subjects randomized to the placebo at baseline.	MECP2 mutation positive subjects randomized to DM at 3 months	MECP2 mutation positive subjects randomized to placebo at 3 months
Measure Participants	13	16	11	16
Mean (Standard Deviation) [seizure count]	3.6 (1.19)	2.8 (1.47)	3.36 (1.12)	3.37 (1.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug-dextromethorphan (DM), Placebo Group, Study Drug Group at 3 Months, Placebo at 3 Months
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; -0.66 to 2.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.68
	Estimation Comments

Adverse Events

Arm/Group Title	Study Drug-dextromethorphan (DM)		Placebo Group		Study Drug Group at 3 Months		Placebo at 3 Months
Arm/Group Description	MECP2 mutation positive subjects randomized to receive dextromethorphan(DM) at baseline		MECP2 positive subjects randomized to the placebo at baseline.		MECP2 mutation positive subjects randomized to DM at 3 months		MECP2 mutation positive subjects randomized to placebo at 3 months
All Cause Mortality
	Study Drug-dextromethorphan (DM)		Placebo Group		Study Drug Group at 3 Months		Placebo at 3 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)		0/24 (0%)		0/26 (0%)
Serious Adverse Events
	Study Drug-dextromethorphan (DM)		Placebo Group		Study Drug Group at 3 Months		Placebo at 3 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)		0/24 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Study Drug-dextromethorphan (DM)		Placebo Group		Study Drug Group at 3 Months		Placebo at 3 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)		18/24 (75%)		22/26 (84.6%)
Blood and lymphatic system disorders
increased platelets	0/26 (0%)	0	0/26 (0%)	0	3/24 (12.5%)	3	2/26 (7.7%)	2
Hepatobiliary disorders
Increased alkaline phosphatase	0/26 (0%)	0	0/26 (0%)	0	3/24 (12.5%)	3	1/26 (3.8%)	1
Nervous system disorders
seizures	0/26 (0%)	0	0/26 (0%)	0	4/24 (16.7%)	4	8/26 (30.8%)	8
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection	0/26 (0%)	0	0/26 (0%)	0	8/24 (33.3%)	8	11/26 (42.3%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.