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Trial Outcomes & Findings for Comparison of Keppra and Clonidine in the Treatment of Tics (NCT NCT00370838)

NCT ID: NCT00370838

Last Updated: 2011-09-07

Results Overview

The YGTSS is a semi-structured clinical interview designed to measure current tic severity \[Leckman et al., 1989\], and consists of separate rating of motor (0-25) and vocal (0-25) tics. Ratings are made along 5 discriminant dimensions, scaled 0-5 for each including number, frequency, intensity, complexity, and interference. Total of these scores (0-50) is a Total Tic Score (TTS). The YGTSS contains an impairment ranking, 0-50 points, based on the impact of the tic disorder on areas such as self esteem, family life, social acceptance, and school. 0=no tics present; 100=most severe tics.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

Results posted on

2011-09-07

Participant Flow

12 participants signed informed consent, but 2 participants were never randomized to treatment arm.

Participant milestones

Participant milestones
Measure
First Levetiracetam Then Clonidine
Participants first received levetiracetam: starting dose of 10 milligram/killigram/day, increased weekly by 5-10 milligram/killigram/day, to a maximum of 50 milligram/killigram/day (25 milligram/killigram twice a day; 2,500 mg per day). In the second period, participants received clonidine (days 65-107), packaged in look-alike capsules: starting dose was 0.05 milligrams twice a day, if needed, the dose increased weekly by 0.05-0.1 milligrams. The maximum dose was 0.4 milligrams (0.2 milligrams twice a day). Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study. Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).
Clonidine First, Then Levetiracetam
Participants first received clonidine, packaged in look-alike capsules: starting dose was 0.05 milligram (mg) twice a day, if needed, the dose increased weekly by 0.05-0.1 mg. The maximum dose was 0.4 mg (0.2 mg twice a day (BID)). In the second period, participants received levetiracetam: starting dose of 10 mg/killigram(kg)/day, increased weekly by 5-10 mg/kg/day, to a maximum of 50 mg/kg/day (25 mg/kg BID; 2,500 mg per day). Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study. Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).
Period 1 (Days 8-50)
STARTED
7
3
Period 1 (Days 8-50)
COMPLETED
7
3
Period 1 (Days 8-50)
NOT COMPLETED
0
0
Washout (Days 51-64)
STARTED
7
3
Washout (Days 51-64)
COMPLETED
7
3
Washout (Days 51-64)
NOT COMPLETED
0
0
Period 2 (Days 65-107)
STARTED
7
3
Period 2 (Days 65-107)
COMPLETED
7
3
Period 2 (Days 65-107)
NOT COMPLETED
0
0
Taper
STARTED
7
3
Taper
COMPLETED
7
3
Taper
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Keppra and Clonidine in the Treatment of Tics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Levetiracetam First, Then Clonidine
n=7 Participants
Participants first received levetiracetam: starting dose of 10 milligram/killigram/day, increased weekly by 5-10 milligram/killigram/day, to a maximum of 50 milligram/killigram/day (25 milligram/killigram twice a day; 2,500 mg per day). In the second period, participants received clonidine (days 65-107), packaged in look-alike capsules: starting dose was 0.05 milligrams twice a day, if needed, the dose increased weekly by 0.05-0.1 milligrams. The maximum dose was 0.4 milligrams (0.2 milligrams twice a day). Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study. Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).
Clonidine First, Then Levetiracetam
n=3 Participants
Participants first received clonidine, packaged in look-alike capsules: starting dose was 0.05 milligram (mg) twice a day, if needed, the dose increased weekly by 0.05-0.1 mg. The maximum dose was 0.4 mg (0.2 mg twice a day (BID)). In the second period, participants received levetiracetam: starting dose of 10 mg/killigram(kg)/day, increased weekly by 5-10 mg/kg/day, to a maximum of 50 mg/kg/day (25 mg/kg BID; 2,500 mg per day). Wash out phase: Between the two treatment phases, medication tapered over a ten day period: levetiracetam by 5-10 mg/kg/day every third day; clonidine by 0.05 - 0.1 mg every third day. Subjects were off medication for 5 days before starting the second phase of the cross over study. Taper: After the two treatment phases, medication tapered over a ten day period as in Wash-out phase (see above).
Total
n=10 Participants
Total of all reporting groups
Age, Categorical
<=18 years
6 Participants
n=99 Participants
2 Participants
n=107 Participants
8 Participants
n=206 Participants
Age, Categorical
Between 18 and 65 years
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Age, Categorical
>=65 years
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Age Continuous
14.5 years
STANDARD_DEVIATION 6.4 • n=99 Participants
16.0 years
STANDARD_DEVIATION 4.4 • n=107 Participants
14.9 years
STANDARD_DEVIATION 5.5 • n=206 Participants
Sex: Female, Male
Female
1 Participants
n=99 Participants
2 Participants
n=107 Participants
3 Participants
n=206 Participants
Sex: Female, Male
Male
6 Participants
n=99 Participants
1 Participants
n=107 Participants
7 Participants
n=206 Participants
Region of Enrollment
United States
7 participants
n=99 Participants
3 participants
n=107 Participants
10 participants
n=206 Participants

PRIMARY outcome

Timeframe: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

The YGTSS is a semi-structured clinical interview designed to measure current tic severity \[Leckman et al., 1989\], and consists of separate rating of motor (0-25) and vocal (0-25) tics. Ratings are made along 5 discriminant dimensions, scaled 0-5 for each including number, frequency, intensity, complexity, and interference. Total of these scores (0-50) is a Total Tic Score (TTS). The YGTSS contains an impairment ranking, 0-50 points, based on the impact of the tic disorder on areas such as self esteem, family life, social acceptance, and school. 0=no tics present; 100=most severe tics.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=10 Participants
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 Participants
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Yale Global Tic Severity Scale (YGTSS):
Baseline
45.2 scores on a scale
Standard Deviation 12.7
48.7 scores on a scale
Standard Deviation 9.6
Yale Global Tic Severity Scale (YGTSS):
Final
48.8 scores on a scale
Standard Deviation 21.8
43.1 scores on a scale
Standard Deviation 11.2

PRIMARY outcome

Timeframe: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

The TTS is a portion of the YGTSS \[Leckman et al., 1989\], and consists of separate rating of motor (0-25) and vocal (0-25) tics. Ratings are made along 5 discriminant dimensions, scaled 0-5 for each including number, frequency, intensity, complexity, and interference. Total of these scores (0-50) is a Total Tic Score (TTS). A score of 0 represent no tics present, a score of 50 represents the most severe tics in each category listed.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=10 Participants
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 Participants
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Total Tic Score
Baseline
22.7 scores on a scale
Standard Deviation 5.7
25.2 scores on a scale
Standard Deviation 4.3
Total Tic Score
Final
23.6 scores on a scale
Standard Deviation 10.6
21.8 scores on a scale
Standard Deviation 4.4

SECONDARY outcome

Timeframe: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

Clinical Global Impression-Improvement (CGI-I): The CGI-I is used to compare current severity to baseline. A score of 1 corresponds to "very much improved; 2 equals "much improved;" 3 denotes minimal change; and 4 represents "no change." Scores above 4 are used to indicate deterioration, i.e., 5 equals "minimally worse;" 6 is "much worse;" and 7 is "very much worse."

Outcome measures

Outcome measures
Measure
Levetiracetam
n=10 Participants
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 Participants
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clinical Global Impression-Improvement (CGI-I):
Baseline
4.1 scores on a scale
Standard Deviation 0.74
4.1 scores on a scale
Standard Deviation 0.6
Clinical Global Impression-Improvement (CGI-I):
Final
4.1 scores on a scale
Standard Deviation 0.74
4 scores on a scale
Standard Deviation 0.5

SECONDARY outcome

Timeframe: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

The severity of obsessive-compulsive disorder (OCD) is evaluated using the CY-BOCS \[Scahill et al 1997\]. Obsessions and compulsions are rated on 5 separate scales yielding three summary scores: Obsessions (0-20), Compulsions (0-20) and Total score (0-40). The CY-BOCS is the most widely used instrument to assess the severity of OCD symptoms in research studies. It includes checklist of specific obsessions and compulsions followed by examiner ratings of time spent, interference, distress, resistance and control over the obsessions and compulsions.0=no obsessions or compulsions; 40=most severe OC

Outcome measures

Outcome measures
Measure
Levetiracetam
n=10 Participants
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 Participants
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS):
Baseline
4.7 scores on a scale
Standard Deviation 5
3.1 scores on a scale
Standard Deviation 4.1
Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS):
Final
2.2 scores on a scale
Standard Deviation 3.7
3.2 scores on a scale
Standard Deviation 4.5

SECONDARY outcome

Timeframe: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

The presence of Attention Deficit Hyperactivity Disorder (ADHD) symptoms are assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) version of the DuPaul ADHD rating scale, which incorporates the symptom items for ADHD from the DSM into a rating scale format that quantifies symptom severity. Each item is rated as not at all, just a little, pretty much, and very much (0, 1, 2, and 3). There are 18 items in total are summed, with a minimum score of 0 (meaning no inattention or hyperactivity) with a maximum score of 54 (severe inattention and hyperactivity).

Outcome measures

Outcome measures
Measure
Levetiracetam
n=10 Participants
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 Participants
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
DuPaul Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale:
Baseline
12.5 scores on a scale
Standard Deviation 10.3
12.6 scores on a scale
Standard Deviation 11.1
DuPaul Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale:
Final
12.7 scores on a scale
Standard Deviation 10.6
11.9 scores on a scale
Standard Deviation 10.6

SECONDARY outcome

Timeframe: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

The child's anxiety will be followed using the multidimensional Anxiety Scale for Children (MASC) (Stallings and March, 1995) and is now considered the preferred instrument for rating childhood anxiety. It is a 39-item questionnaire, ranking each item as "Never", "Rarely", "Sometimes", or "Often" (0, 1, 2, 3). The sum of all responses yeilds a score (maximum MASC score is 117). A score of 0 represents no anxiety, and a score of 117 represents severe anxiety.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=10 Participants
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 Participants
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Multidimensional Anxiety Scale for Children (MASC):
Baseline
32.9 scores on a scale
Standard Deviation 15.4
25.2 scores on a scale
Standard Deviation 17.1
Multidimensional Anxiety Scale for Children (MASC):
Final
27.5 scores on a scale
Standard Deviation 16.2
25 scores on a scale
Standard Deviation 14.7

SECONDARY outcome

Timeframe: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106)

Side effects will be assessed by an expanded (modified) Pittsburgh Side Effect Scale modified to include side effects of levetiracetam and clonidine. Significant adverse events will be reported to the UCB, JCCI, and FDA within 24 hours. Positive responses are tallied as "number of side effects" for the responding period.

Outcome measures

Outcome measures
Measure
Levetiracetam
n=10 Participants
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 Participants
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Modified Pittsburgh Side Effect Scale
2.1 Number of Side Effects
Standard Deviation 2.1
3.4 Number of Side Effects
Standard Deviation 4.5

Adverse Events

Levetiracetam

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Clonidine

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Levetiracetam
n=10 participants at risk
Participants received levetiracetam in either first or second period of this study. The initial dose of levetiracetam was 10 mg/kg/day, divided twice daily (rounded to the closest unit of 250 mg). The dose was increased weekly by 5-10 mg/kg/day, to a maximum dose of 50 mg/kg/day (or 2,500 mg/day), if deemed necessary for tic suppression. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
Clonidine
n=10 participants at risk
Participants received clonidine in either the first or second phase of the study. The initial dose of clonidine was 0.05 mg, twice daily. If needed for tic suppression, the dose was increased weekly by 0.05-0.1 mg, with a maximum dose of 0.4 mg per day. In any individual, dose escalation may have proceeded more slowly, or the dose may have been reduced as necessary. No changes in dosage occurred during the final week of either treatment phase.
General disorders
Irritability
30.0%
3/10 • Number of events 7
20.0%
2/10 • Number of events 2
General disorders
Sad/depressed
20.0%
2/10 • Number of events 4
10.0%
1/10 • Number of events 1
General disorders
Hyperactive
20.0%
2/10 • Number of events 2
0.00%
0/10
General disorders
Tired/sleepy
20.0%
2/10 • Number of events 2
50.0%
5/10 • Number of events 17
General disorders
Anxious
30.0%
3/10 • Number of events 3
40.0%
4/10 • Number of events 4
General disorders
Lethargic
10.0%
1/10 • Number of events 1
20.0%
2/10 • Number of events 2
General disorders
Fatigue
10.0%
1/10 • Number of events 2
30.0%
3/10 • Number of events 3
General disorders
Dizzy
10.0%
1/10 • Number of events 1
10.0%
1/10 • Number of events 2
Psychiatric disorders
Aggression
20.0%
2/10 • Number of events 5
30.0%
3/10 • Number of events 3
General disorders
Stomache ache
0.00%
0/10
20.0%
2/10 • Number of events 2
General disorders
Dry mouth
10.0%
1/10 • Number of events 1
10.0%
1/10 • Number of events 1
General disorders
Insomnia
20.0%
2/10 • Number of events 2
20.0%
2/10 • Number of events 5
General disorders
Loss of appetite
10.0%
1/10 • Number of events 1
0.00%
0/10
General disorders
Sleepwalking
0.00%
0/10
10.0%
1/10 • Number of events 1

Additional Information

Dr. Harvey Singer

Johns Hopkins University

Phone: 410-955-7212

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place