Comparison of Keppra and Clonidine in the Treatment of Tics

NCT00370838 | Completed Phase 4 Results DMC

• 1 other identifier: TSkepclon
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tic Disorders; Tourette Syndrome

Keywords

Tics; Tourette syndrome; levetiracetam; clonidine

Outcome Measures

Primary Outcomes (2)

• Yale Global Tic Severity Scale (YGTSS):

  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.

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

• Total Tic Score

  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.

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

Secondary Outcomes (5)

• Clinical Global Impression-Improvement (CGI-I):

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

• Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS):

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

• DuPaul Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale:

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

• Multidimensional Anxiety Scale for Children (MASC):

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

• Modified Pittsburgh Side Effect Scale

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

Study Arms (2)

Levetiracetam

EXPERIMENTAL

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

Clonidine

ACTIVE COMPARATOR

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

Interventions

Levetiracetam DRUG

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.

Also known as: Levetiracetam (Keppra)

Levetiracetam

Clonidine DRUG

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.

Also known as: Catapres

Clonidine

Eligibility Criteria

• Age: 7 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Harvey S. Singer: lead
• UCB Pharma: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Tic Disorders; Tourette Syndrome; Tics

Interventions

Levetiracetam; Clonidine

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurodevelopmental Disorders; Mental Disorders; Basal Ganglia Diseases; Brain Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazolines; Imidazoles; Azoles

Results Point of Contact

• Title: Dr. Harvey Singer
• Organization: Johns Hopkins University

hsinger@jhmi.edu

410-955-7212

Study Officials

• Harvey S Singer, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Haller Professor of Pediatric Neurology

Study Record Dates

• First Submitted: August 30, 2006
• First Posted: September 1, 2006
• Study Start: February 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: June 1, 2009
• Last Updated: September 7, 2011
• Results First Posted: September 7, 2011

Record last verified: 2011-09

Locations

US (1)