Comparison of Keppra and Clonidine in the Treatment of Tics - Full Text View

Sponsor:	Harvey S. Singer
Collaborator:	UCB, Inc.
Information provided by (Responsible Party):	Harvey S. Singer, Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00370838

Purpose

The goal of this study is to confirm that levetiracetam has a better tic-suppressing profile than that of the widely used tic-suppressing medication, clonidine. More specifically, the investigators hypothesize that in a 15 week placebo run-in, double-blind, medication cross-over trial; levetiracetam will be more effective and have fewer side-effects than clonidine.

Condition	Intervention	Phase
Tic Disorders Tourette Syndrome	Drug: Levetiracetam Drug: Clonidine	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Comparison of Keppra and Clonidine in the Treatment of Tics in Children With Tourette Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia

MedlinePlus related topics: Tourette Syndrome

Drug Information available for: Clonidine Clonidine hydrochloride Levetiracetam

U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

Yale Global Tic Severity Scale (YGTSS): [ Time Frame: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106) ] [ Designated as safety issue: No ]
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.
Total Tic Score [ Time Frame: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106) ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Clinical Global Impression-Improvement (CGI-I): [ Time Frame: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106) ] [ Designated as safety issue: No ]
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."
Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS): [ Time Frame: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106) ] [ Designated as safety issue: No ]
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
DuPaul Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale: [ Time Frame: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106) ] [ Designated as safety issue: No ]
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).
Multidimensional Anxiety Scale for Children (MASC): [ Time Frame: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106) ] [ Designated as safety issue: No ]
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.
Modified Pittsburgh Side Effect Scale [ Time Frame: Baseline (Day 8 or Day 64), Final (6 weeks later: Day 50 or Day 106) ] [ Designated as safety issue: Yes ]
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.

Enrollment:	12
Study Start Date:	February 2007
Study Completion Date:	June 2009
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Levetiracetam Levetiracetam (Keppra) is used in one phase of this cross-over 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.	Drug: Levetiracetam 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. Other Name: Levetiracetam (Keppra)
Active Comparator: Clonidine Clonidine is used in one phase of this cross-over 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.	Drug: Clonidine 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. Other Name: Catapres

Arms

Assigned Interventions

Experimental: Levetiracetam

Levetiracetam (Keppra) is used in one phase of this cross-over 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.

Drug: Levetiracetam

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.

Other Name: Levetiracetam (Keppra)

Active Comparator: Clonidine

Clonidine is used in one phase of this cross-over 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.

Drug: Clonidine

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.

Other Name: Catapres

Show Detailed Description

Eligibility

Ages Eligible for Study:	7 Years to 19 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients will be included in this study if they meet the following criteria:

Tourette syndrome criteria based on the TS Classification Study Group [1993], which includes onset before 18 years, multiple involuntary motor tics, one or more vocal tics, a waxing and waning course, the gradual replacement of old symptoms with new ones, the presence of tics for more than one year, the absence of other medical explanations for tics, and observation of tics by a reliable examiner;
Age 7 to 19 years, either gender;
Observable tics, achieving a minimum score of > 22 on the Total Tic score of Yale Global Tic Severity Scale (YGTSS);
Tic symptoms severe enough to warrant therapy;
The concurrent use of other tic-suppressing medications will be permitted, if the subject has been on a stable dose for more than three weeks and agrees to maintain a constant dosage throughout the study;
Tics are not controlled with current medication or individuals are tic suppressing drug naive.

Exclusion Criteria:

Exclusion criteria include the following:

Secondary tics;
Significant medical illness
Current major depression, generalized anxiety disorder, separation anxiety disorder, psychotic symptoms (based on clinical evaluation), pervasive developmental disorder, autism, mental retardation (I.Q. less than 70), anorexia/bulimia, or substance abuse. Subjects with co-morbid ADHD, obsessive compulsive disorder (OCD), and conduct disorder will not be excluded;
pregnancy;
Hypersensitivity to levetiracetam or clonidine;
baseline weight of less than 25 kilograms.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00370838

Locations

United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Harvey S. Singer

UCB, Inc.

Investigators

Principal Investigator:

Harvey S Singer, MD

Johns Hopkins University

More Information

No publications provided

Responsible Party:	Harvey S. Singer, Haller Professor of Pediatric Neurology, Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00370838 History of Changes
Other Study ID Numbers:	TSkepclon
Study First Received:	August 30, 2006
Results First Received:	June 22, 2011
Last Updated:	September 1, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Johns Hopkins University:

Tics
Tourette syndrome
levetiracetam
clonidine

Additional relevant MeSH terms:

Tic Disorders
Tics
Tourette Syndrome
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases

Genetic Diseases, Inborn
Clonidine
Etiracetam
Piracetam
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists

ClinicalTrials.gov processed this record on May 24, 2012