Comparison of Keppra and Clonidine in the Treatment of Tics in Children With Tourette Syndrome
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Yale Global Tic Severity Scale (YGTSS):
研究概览
简要总结
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.
详细描述
This is a randomized, double-blind, 15 week (two treatment phase), 1 week run-in, cross-over study, in which the same patient receives 6 weeks of treatment with levetiracetam and a 6 week treatment course with clonidine, separated by a two week medication wash-out. The investigators plan to enroll twenty patients between the ages of 7 to 19 years with moderate to moderately-severe Tourette syndrome or chronic motor/vocal tics. The recruitment period is expected to be approximately 12 months (total study length of about 18 months). The study will begin with a screening evaluation to ensure that each subject satisfies all eligibility criteria, to allow subjects to become familiar with our assessment procedures, and to obtain informed consent. Following a baseline visit, there will be a one week "run-in" treatment period in order to screen for high placebo responders, in which all subjects will receive placebo. If the patient's tic severity score fails to improve he/she will begin the double blind treatment period (levetiracetam/clonidine), that will last for six weeks followed by a two week wash out period, and then by a second double blind treatment period (clonidine/levetiracetam) for an additional six weeks. A statistician not involved with the care of the subjects will be responsible for randomization. A six week trial treatment was chosen to allow for an adequate drug response period. Patients will be followed by phone at weekly intervals throughout the study and will be formally evaluated at the beginning and end of each treatment phase. At the completion of the study, patients/parents will be given the opportunity to continue a successful treatment.
The primary outcome measure is the Yale Global Tic Severity Scale (YGTSS): A semi-structured clinical interview designed to measure current tic severity. Other outcome measures will include the Clinical Global Impression-Improvement Scale (CGI-I), the Child Yale-Brown Obsessive-Compulsive Scale (CYBOCS), the DuPaul Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale, Child Depression Inventory (CDI), Multi-Dimensional Anxiety Scale for Children (MASC), and an expanded Pittsburgh Side-Effect Scale.
Subjects will be recruited from the Tourette Syndrome Clinic at the Johns Hopkins Hospital. This clinic, directed by Dr. Harvey Singer, currently follows more than 1000 chronic tic patients and averages 4 new referrals every week. The clinic staff has a longstanding successful record of designing and completing therapeutic protocols for the treatment of tics.
Inclusion Criteria: see below
Exclusion Criteria: see below
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 7 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Levetiracetam (Drug)
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.
干预措施: Clonidine (Drug)
结局指标
主要结局
Yale Global Tic Severity Scale (YGTSS):
时间窗: 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.
Total Tic Score
时间窗: 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.
次要结局
- 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))
研究者
Harvey S. Singer
Haller Professor of Pediatric Neurology
Johns Hopkins University