Trial Outcomes & Findings for Trial of Dextromethorphan in Rett Syndrome (NCT NCT00593957)
NCT ID: NCT00593957
Last Updated: 2014-04-23
Results Overview
Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
38 participants
Primary outcome timeframe
Initial and 6-month post-treatment
Results posted on
2014-04-23
Participant Flow
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.
Pharmacokinetics in enrolled subjects required her to be a fast metabolizer of Dextromethorphan (DM).
Participant milestones
| Measure |
DM1( 0.25 mg/kg /Day)
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.
|
DM2 (2.5 mg/kg/Day)
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.
|
DM3 (5mg/kg/Day)
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 Study
STARTED
|
13
|
13
|
12
|
|
Overall Study
COMPLETED
|
13
|
12
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
2
|
Reasons for withdrawal
| Measure |
DM1( 0.25 mg/kg /Day)
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.
|
DM2 (2.5 mg/kg/Day)
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.
|
DM3 (5mg/kg/Day)
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 Study
Physician Decision
|
0
|
1
|
2
|
Baseline Characteristics
Trial of Dextromethorphan in Rett Syndrome
Baseline characteristics by cohort
| Measure |
DM1( 0.25 mg/kg /Day)
n=13 Participants
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.
|
DM2 (2.5 mg/kg/Day)
n=13 Participants
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.
|
DM3 (5mg/kg/Day)
n=12 Participants
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
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
13 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
38 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Continuous
|
6.54 years
STANDARD_DEVIATION 2.70 • n=93 Participants
|
6.31 years
STANDARD_DEVIATION 3.50 • n=4 Participants
|
6.08 years
STANDARD_DEVIATION 3.06 • n=27 Participants
|
6.32 years
STANDARD_DEVIATION 3.02 • n=483 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
38 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=93 Participants
|
13 participants
n=4 Participants
|
12 participants
n=27 Participants
|
38 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Initial and 6-month post-treatmentPopulation: 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.
Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.
Outcome measures
| Measure |
Dextromethorphan (DM)1 EEG Spike Counts at Baseline
n=13 Participants
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 EEG Spike Counts at Baseline
n=12 Participants
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 EEG Spike Counts at Baseline
n=8 Participants
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 EEG Spike Count at 6 Months
n=13 Participants
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 EEG Spike Counts at 6 Months
n=12 Participants
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 EEG Spike Counts at 6 Months
n=8 Participants
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.
|
|---|---|---|---|---|---|---|
|
Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.
|
44.22 EEG spike counts per minute
Standard Deviation 23.77
|
25.44 EEG spike counts per minute
Standard Deviation 18.6
|
40.67 EEG spike counts per minute
Standard Deviation 27.83
|
38.29 EEG spike counts per minute
Standard Deviation 30.24
|
27.58 EEG spike counts per minute
Standard Deviation 19.52
|
36.01 EEG spike counts per minute
Standard Deviation 23.29
|
SECONDARY outcome
Timeframe: Change in mean between Initial and 6-month follow-upPopulation: 25/35 enrolled participants completed the receptive language scale of the Mullen and underwent the analysis.
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.
Outcome measures
| Measure |
Dextromethorphan (DM)1 EEG Spike Counts at Baseline
n=10 Participants
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 EEG Spike Counts at Baseline
n=8 Participants
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 EEG Spike Counts at Baseline
n=7 Participants
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 EEG Spike Count at 6 Months
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 EEG Spike Counts 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 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.
|
|---|---|---|---|---|---|---|
|
Improvement in Receptive Language as Measured by the Mullen Scale.
|
0 age in months
Standard Deviation 2.94
|
-0.44 age in months
Standard Deviation 2.96
|
03 age in months
Standard Deviation 2.45
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Initial and 6 month followupPopulation: Those who provided complete information only were included. Others did not provide adequate or complete information for analysis.
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.
Outcome measures
| Measure |
Dextromethorphan (DM)1 EEG Spike Counts at Baseline
n=8 Participants
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 EEG Spike Counts at Baseline
n=4 Participants
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 EEG Spike Counts at Baseline
n=7 Participants
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 EEG Spike Count at 6 Months
n=8 Participants
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 EEG Spike Counts at 6 Months
n=4 Participants
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 EEG Spike Counts at 6 Months
n=7 Participants
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.
|
|---|---|---|---|---|---|---|
|
Difference in SSI Mean Score at Six Months Compared to Baseline for Each Treatment Arm.
|
40.25 scores on a scale
Standard Deviation 18.59
|
70.00 scores on a scale
Standard Deviation 19.10
|
84.29 scores on a scale
Standard Deviation 17.51
|
48.63 scores on a scale
Standard Deviation 18.58
|
74.50 scores on a scale
Standard Deviation 22.78
|
88.29 scores on a scale
Standard Deviation 18.88
|
SECONDARY outcome
Timeframe: 0-6 monthsPopulation: 19 subjects (total sample) for whom complete data was available
Analysis of Difference in Mean Screen for Social Interaction (SSI) Score between 0-6 months for total sample (n=19).
Outcome measures
| Measure |
Dextromethorphan (DM)1 EEG Spike Counts at Baseline
n=19 Participants
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 EEG Spike Counts at Baseline
n=19 Participants
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 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 EEG Spike Count at 6 Months
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 EEG Spike Counts 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 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.
|
|---|---|---|---|---|---|---|
|
Mean SSI Score for Total Subjects at Baseline and 6 Months
|
62.737 scores on a scale
Standard Deviation 26.729
|
68.684 scores on a scale
Standard Deviation 25.987
|
—
|
—
|
—
|
—
|
Adverse Events
DM1( 0.25 mg/kg /Day)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DM2 (2.5 mg/kg/Day)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DM3 (5mg/kg/Day)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr Sakkubai Naidu Professor of Neurology and Pediatrics
Kennedy Krieger Institute
Phone: 443-923-2778
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place