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Trial of Dextromethorphan in Rett Syndrome

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ClinicalTrials.gov Identifier: NCT00593957
Recruitment Status : Terminated (Study changed to a placebo controlled trial of dextromethorphan)
First Posted : January 15, 2008
Results First Posted : April 23, 2014
Last Update Posted : April 23, 2014
Sponsor:
Information provided by (Responsible Party):
SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rett Syndrome
Intervention Drug: Dextromethorphan
Enrollment 38
Recruitment Details Recruitment was from 2004 to 2010. Study initiation was delayed due to the closure of Johns Hopkins Medicine Institutional Review Board(JHMIRB). Patients were recruited from our Kennedy Krieger Institute (KKI)medical clinics, physician referrals,and parent organizations. Parents were sent letters of invitation.
Pre-assignment Details Pharmacokinetics in enrolled subjects required her to be a fast metabolizer of Dextromethorphan (DM).
Arm/Group Title DM1( 0.25 mg/kg /Day) DM2 (2.5 mg/kg/Day) DM3 (5mg/kg/Day)
Hide Arm/Group Description

Dextromethorphan 0.25 mg/kg per day

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

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

Dextromethorphan 2.5 mg/kg/day

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

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

Dextromethorphan 5mg/kg/day

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

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

Period Title: Overall Study
Started 13 13 12
Completed 13 12 10
Not Completed 0 1 2
Reason Not Completed
Physician Decision             0             1             2
Arm/Group Title DM1( 0.25 mg/kg /Day) DM2 (2.5 mg/kg/Day) DM3 (5mg/kg/Day) Total
Hide Arm/Group Description

Dextromethorphan 0.25 mg/kg per day

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

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

Dextromethorphan 2.5 mg/kg/day

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

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

Dextromethorphan 5mg/kg/day

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

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

Total of all reporting groups
Overall Number of Baseline Participants 13 13 12 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 12 participants 38 participants
<=18 years
13
 100.0%
13
 100.0%
12
 100.0%
38
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 13 participants 12 participants 38 participants
6.54  (2.70) 6.31  (3.50) 6.08  (3.06) 6.32  (3.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 12 participants 38 participants
Female
13
 100.0%
13
 100.0%
12
 100.0%
38
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 13 participants 12 participants 38 participants
13 13 12 38
1.Primary Outcome
Title Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.
Hide Description Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.
Time Frame Initial and 6-month post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
33/35 participants who completed the protocol with two epochs of 5 mins of non-Rapid eye movement (REM)sleep during which spikes could be counted pre and post DM intake.
Arm/Group Title Dextromethorphan (DM)1 EEG Spike Counts at Baseline DM2 EEG Spike Counts at Baseline DM3 EEG Spike Counts at Baseline DM1 EEG Spike Count at 6 Months DM2 EEG Spike Counts at 6 Months DM3 EEG Spike Counts at 6 Months
Hide Arm/Group Description:
Dextromethorphan(DM)I group received Dextromethorphan 0.25 mg/kg per day. The drug is given in two divided doses 12 hours apart for 6 months. EEG spike count for DM1 group measured at baseline.
DM2 group participants received Dextromethorphan 2.5 mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months. DM2 EEG spike counts at baseline.

DM3 group received Dextromethorphan 5mg/kg/day.

The drug is given in two divided doses 12 hours apart for 6 months. EEG spike counts at baseline.

DM1 group received Dextromethorphan 0.25 mg/kg per day. The drug is given in two divided doses 12 hours apart for 6 months. EEG spike count for DM1 group measured at 6 months.
DM2 group participants received Dextromethorphan 2.5 mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months. DM2 EEG spike counts at 6 months.
DM3 group received Dextromethorphan 5mg/kg/day. The drug is given in two divided doses 12 hours apart for 6 months. EEG spike counts at 6 months.
Overall Number of Participants Analyzed 13 12 8 13 12 8
Mean (Standard Deviation)
Unit of Measure: EEG spike counts per minute
44.22  (23.77) 25.44  (18.6) 40.67  (27.83) 38.29  (30.24) 27.58  (19.52) 36.01  (23.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dextromethorphan (DM)1 EEG Spike Counts at Baseline, DM1 EEG Spike Count at 6 Months
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.40
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DM2 EEG Spike Counts at Baseline, DM2 EEG Spike Counts at 6 Months
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.62
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DM3 EEG Spike Counts at Baseline, DM3 EEG Spike Counts at 6 Months
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.38
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Improvement in Receptive Language as Measured by the Mullen Scale.
Hide Description The Mullen Receptive language scale pre and 6 months post DM, measured as a change in the mean score of language, by age in months.
Time Frame Change in mean between Initial and 6-month follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
25/35 enrolled participants completed the receptive language scale of the Mullen and underwent the analysis.
Arm/Group Title DM1( 0.25 mg/kg /Day) DM2 (2.5 mg/kg/Day) DM3 (5mg/kg/Day)
Hide Arm/Group Description:

Dextromethorphan 0.25 mg/kg per day

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

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

Dextromethorphan 2.5 mg/kg/day

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

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

Dextromethorphan 5mg/kg/day

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

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

Overall Number of Participants Analyzed 10 8 7
Mean (Standard Deviation)
Unit of Measure: age in months
0  (2.94) -0.44  (2.96) 03  (2.45)
3.Secondary Outcome
Title Difference in SSI Mean Score at Six Months Compared to Baseline for Each Treatment Arm.
Hide Description The Screen for Social Interaction (SSI) is a 54-item parent/caregiver-report screening instrument that emphasizes reciprocal social interaction including joint attention skills. The items are positive (prosocial) and are scored on a four-point frequency scale (child displays the behavior “almost never” = 0 to “almost all the time” = 3). Thus lower scores reflect a slower or delayed development, and higher scores reflect more normative development. SSI total scores range from 0-162. There are no subscales. Difference in Screen for Social Interaction (SSI) mean scores between baseline and 6 months post-treatment for each treatment arm are reported.
Time Frame Initial and 6 month followup
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Those who provided complete information only were included. Others did not provide adequate or complete information for analysis.
Arm/Group Title DM1( 0.25 mg/kg /Day) SSI Baseline DM2 (2.5 mg/kg/Day)SSI Baseline DM3 (5mg/kg/Day) SSI Baseline DM1( 0.25 mg/kg /Day) SSI 6 Months DM2 (2.5 mg/kg/Day) SSI 6 Months DM3 (5.0 mg/kg/Day) SSI 6 Months
Hide Arm/Group Description:
Screen for Social Interaction (SSI) mean score at baseline for Dextromethorphan 0.25 mg/kg per day treatment arm.
Screen for Social Interaction (SSI) mean score at baseline for Dextromethorphan 2.5 mg/kg/day treatment arm.
Screen for Social Interaction (SSI) mean score at baseline for Dextromethorphan 5mg/kg/day treatment arm.
DM1( 0.25 mg/kg /day)treatment arm Screen for Social Interaction (SSI) mean score at 6 months post-treatment.
DM2( 2.5 mg/kg /day)treatment arm Screen for Social Interaction (SSI) mean score at 6 months post-treatment.
DM3(5.0) mg/kg /day)treatment arm Screen for Social Interaction (SSI) mean score at 6 months post-treatment.
Overall Number of Participants Analyzed 8 4 7 8 4 7
Mean (Standard Deviation)
Unit of Measure: scores on a scale
40.25  (18.59) 70.00  (19.10) 84.29  (17.51) 48.63  (18.58) 74.50  (22.78) 88.29  (18.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DM1( 0.25 mg/kg /Day) SSI Baseline, DM1( 0.25 mg/kg /Day) SSI 6 Months
Comments Null hypothesis is that there would be no significant difference in social abilities as measured by the SSI score in this treatment group baseline to 6 months post-treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.10
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DM2 (2.5 mg/kg/Day)SSI Baseline, DM2 (2.5 mg/kg/Day) SSI 6 Months
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.50
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DM3 (5mg/kg/Day) SSI Baseline, DM3 (5.0 mg/kg/Day) SSI 6 Months
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.48
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean SSI Score for Total Subjects at Baseline and 6 Months
Hide Description Analysis of Difference in Mean Screen for Social Interaction (SSI) Score between 0-6 months for total sample (n=19).
Time Frame 0-6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
19 subjects (total sample) for whom complete data was available
Arm/Group Title Total Sample SSI Mean Score at Baseline Total Sample SSI Mean Score at 6 Months
Hide Arm/Group Description:
Study Sample Screen for Social Interaction (SSI) mean core at baseline.
Study Sample Screen for Social Interaction (SSI) mean score at 6 months post-treatment.
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: scores on a scale
62.737  (26.729) 68.684  (25.987)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Sample SSI Mean Score at Baseline, Total Sample SSI Mean Score at 6 Months
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.947
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DM1( 0.25 mg/kg /Day) DM2 (2.5 mg/kg/Day) DM3 (5mg/kg/Day)
Hide Arm/Group Description

Dextromethorphan 0.25 mg/kg per day

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

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

Dextromethorphan 2.5 mg/kg/day

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

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

Dextromethorphan 5mg/kg/day

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

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

All-Cause Mortality
DM1( 0.25 mg/kg /Day) DM2 (2.5 mg/kg/Day) DM3 (5mg/kg/Day)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DM1( 0.25 mg/kg /Day) DM2 (2.5 mg/kg/Day) DM3 (5mg/kg/Day)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/12 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
DM1( 0.25 mg/kg /Day) DM2 (2.5 mg/kg/Day) DM3 (5mg/kg/Day)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/12 (0.00%)   0/10 (0.00%) 
The trial was terminated due to the FDA requiring a placebo controlled trial instead of the ongoing open label trial. As recruitment was delayed,the total number of participants was also less than anticipated.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr Sakkubai Naidu Professor of Neurology and Pediatrics
Organization: Kennedy Krieger Institute
Phone: 443-923-2778
Responsible Party: SakkuBai Naidu, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier: NCT00593957     History of Changes
Other Study ID Numbers: FD2408
First Submitted: January 4, 2008
First Posted: January 15, 2008
Results First Submitted: March 8, 2013
Results First Posted: April 23, 2014
Last Update Posted: April 23, 2014