Ignite Creation Date:
2024-05-05 @ 5:02 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00370838
Status:
COMPLETED
Last Update Posted:
2011-09-07
First Post:
2006-08-30
Brief Title:
Comparison of Keppra and Clonidine in the Treatment of Tics
Sponsor:
Harvey S Singer
Organization:
Johns Hopkins University
Study Overview
Official Title:
Comparison of Keppra and Clonidine in the Treatment of Tics in Children With Tourette Syndrome
Status:
COMPLETED
Status Verified Date:
2011-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
Detailed Description:
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 motorvocal 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 patients tic severity score fails to improve heshe will begin the double blind treatment period levetiracetamclonidine that will last for six weeks followed by a two week wash out period and then by a second double blind treatment period clonidinelevetiracetam 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 patientsparents 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
Procedures
i Screening visit Determination of diagnostic eligibility criteria medical history and complete physical examination evaluation of tic severity screening of females who have begun to menstruate with a urine pregnancy test familiarization with assessment procedures and obtaining informed consent The urine pregnancy test will be obtained in females over 12 years of age Parents will be told the results of these tests If the patient is uncomfortable with our telling the results of the pregnancy test to her parents then they may decide not to take part in this study
ii Baseline Visit Day 0 Evaluation prior to the run-in placebo phase will include weight heart rate blood pressure respiratory rate rating scales for tics the Yale Global Tic Severity Scale YGTSS and Childhood Global Impression-TS CGI-TS adverse effects the Pittsburgh Side-Effect Rating Scale obsessive-compulsive problems Child Yale-Brown Obsessive Compulsive Scale CY-BOCS attention deficit hyperactivity disorder DuPaul ADHD Rating Scale depression Child Depression Inventory- Short Version CDI-S anxiety the Multidimensional Anxiety Scale for Children MASC and episodic outbursts Rage Attack Rating Scale
iii Run-in Placebo Phase days 0-7 Immediately after the baseline visit the subject is started on placebo treatment for a one week period All subjects will receive 1 capsule twice a day capsules will be similar in appearance to that used in the drug treatment phase The Run-in phase has been added to eliminate subjects whose treatment outcome could be influenced by only a transient exacerbation of tics or by the exposure to non-pharmacologic treatment
a Post- Run in Period Evaluation day 8 Subjects will return for a re-evaluation of symptoms emphasis will be placed on rating scales for tics the Yale Global Tic Severity Scale YGTSS and Childhood Global Impression-TS CGI-TS and adverse effects the Pittsburgh Side-Effect Rating Scale If there is no tic improvement following the receipt of placebo the patient will move on to the treatment phase of the study In contrast if tic symptoms are reduced by more than 15 or significant side effects are reported all treatment will be discontinued and the subject will be withdrawn from the study
iv Treatment phases days 8 50 and days 65 107 A computer generated unequal randomized scheme will be used to assign patients to either levetiracetam or clonidine in the initial treatment phase Research Pharmacy at Johns Hopkins will be responsible for packaging levetiracetam supplied by UCB and clonidine purchased randomizing its allocation and distributing the medication Levetiracetam and clonidine will be repackaged in look-alike capsules with different dosage levels levetiracetam 250 milligrams mg or 500 mg and clonidine 005 mg or 01 mg Patients will receive a six week supply of medication at the first treatment phase visit day 8 and at the beginning of the second treatment phase day 63 A study physician Dr Harvey Singer will be responsible for changing medication dosage and monitoring side-effects A Safety Monitoring Board has been established to oversee medication use and monitor side-effects
1 Levetiracetam The starting dose of levetiracetam will be 10 mgkgday for one week administered as 5 mgkg twice a day BIDrounded to the closest unit of 250 mg If needed for tic suppression the dose will be increased weekly by 5-10 mgkilligramskgday The maximum dose will be 50 mgkgday administered as 25 mgkg BID with a maximum dose of 2500 milligrams per day For reference doses from 10 to 60 mgkgday of levetiracetam are currently being used in pediatric studies for the treatment of seizures and up to 2000 mg in TS children with a mean age of 12 years In any individual subject dose escalation may proceed more slowly or the dose may be reduced if necessary No changes in dosage will be made during the final week of both treatment phases
2 Clonidine The starting dose of clonidine will be 005mg BID for one week If needed for tic suppression the dose will be increased weekly by 005-01 mg The maximum dose will be 04 mg administered as 02 mg BID
iv Wash out phase Between the two treatment phases medication will be tapered over a ten day period Levetiracetam will be tapered at the end of each treatment phase by 5-10 mgkgday every third day The half life of levetiracetam is approximately 7-8 hours in healthy volunteers 5 8 hours in epileptic patients and about 10 hours in the elderly Clonidine will be tapered by 005 - 01 mg every third day Subjects will be off medication for 5 days before starting the second phase of the cross over study
v End of study drug taper At the completion of the second treatment phase medication will be tapered over a ten-day period reducing the medications in equal proportions every third day
vi Early stopping rules Subjects may be withdrawn from the study at any time at the discretion of the subject attending physician or investigator
1 The investigator decides the subject should be withdrawn This decision could be made because of an adverse effect or a failure to comply with the study protocol
2 The subject or hisher personal physician requests that the subject be withdrawn from the study
3 The subject for any reason requires treatment with another therapeutic agent that could conflict with the use of levetiracetam or clonidine
4 A Drug Safety Monitoring Board will monitor side effects and assist in determining whether a subject should be withdrawn from the trial Members of this board are full time Johns Hopkins Hospital faculty members and epilepsy fellows with experience in the use of levetiracetam The Board will have access to the randomization codes maintained by the statistician A quarterly update meeting will be scheduled for the Monitoring Board with topics to be reviewed including the number of subjects dosage schedules side effects and therapeutic responses Significant adverse events will be reported to the sponsor Union chimique belge Inc UCB Inc Johns Hopkins Joint Committee on Clinical Investigation JCCI and Food and Drug Administration FDA within 24 hours
vii Evaluations This is a 15 week study Telephone evaluations will be performed by the blinded Research Assistant on day 14 21 28 35 42 70 77 84 91 and 98 At each telephone session clinical response possible side effects drug compliance and medication adjustment will be discussed Subjects will be formally evaluated at 4 separate times including baseline day 0 at end of the run-in phase day 8 end of the first treatment phase day 49 at end of the drug wash out period day 63 and at end of the study day 105 Evaluations at each visit by the Research Assistant will include vital signs weight and an assessment of side effects using the Pittsburgh side effects scale The blinded outcome evaluator Dr Harvey Singer will administer and score the YGTSS CGI I DuPaul ADHD scale CY BOCS CDI S and MASC In addition at each visit a pill count will be done to assure compliance
C Outcomes Measures
i Yale Global Tic Severity Scale YGTSS The YGTSS is a semi-structured clinical interview designed to measure current tic severity Leckman et al 1989 This scale consists of the separate rating of severity for motor total motor 0 to 25 and vocal total vocal 0 to 25 tics Ratings are made along 5 discriminant dimensions on a scale of 0 to 5 for each including number frequency intensity complexity and interference Summation of these scores ie 0 to 50 provides a Total Tic Score TTS which will be the primary outcome measure The YGTSS also contains a separate ranking of impairment Tic Impairment Score or TIS with a maximum of 50 points based on the impact of the tic disorder on areas such as self esteem family life social acceptance and school scores Because the focus of this study is to evaluate the impact of levetiracetam and clonidine on tics and because the TIS may incorporate other components of TS the Total Tic Score TTS has been selected as the primary outcome measure
ii 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 ie 5 equals minimally worse 6 is much worse and 7 is very much worse
iii Child Yale-Brown Obsessive Compulsive Scale The severity of OCD will be evaluated using the Child Yale-Brown Obsessive Compulsive Scale 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 a Total score 0-40 The CY-BOCS is the most widely used instrument to assess the severity of obsessive-compulsive symptoms in research studies involving children It includes a checklist of specific obsessions and compulsions followed by examiner ratings of time spent interference distress resistance and control over the obsessions and compulsions assessed independently The CY-BOCS has well established psychometric properties
iv DuPaul ADHD Rating Scale The presence of ADHD symptoms will be assessed using the DSM-IV version of the ADHD rating scale developed by DuPaul This scale 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 This scale has been normed in large clinical and community samples and has excellent psychometric properties including a test-retest reliability over a 2-week period of 093 and significant correlations with direct observations of classroom behavior
v Child Depression Inventory-Short Version CDI-S Depression severity will be rated by using the Child Depression Inventory-Short Version CDI-S This 10 item scale takes about 5 minutes to complete It has excellent psychometric properties and is designed for repeated administrations over time
vi Multidimensional Anxiety Scale for Children MASC The childs anxiety will be followed using the multidimensional Anxiety Scale for Children MASC and is now considered the preferred instrument for rating childhood anxiety
vii Adverse effects Side effects will be assessed by an expanded 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
D Open Label Continuation
At the completion of the study the subject will be given the option of continuing either levetiracetam or clonidine in an open labeled fashion This will be enabled by having the subject seen by another physician who will have access to the study codes This physician will continue to follow the subject until the entire study is completed For members of the research team the treatment code will not be broken until all subjects have completed the protocol
IV Analytical Strategies A Inclusion of a Run-in phase The Run-in phase has been added to eliminate subjects whose treatment outcome could be influenced by a transient exacerbation of tics or by the exposure to non-pharmacologic treatment
B Power calculations As described this is a pilot randomized double-blind placebo-controlled cross-over project in which the investigators plan to enroll twenty patients between the ages of 7-19 years with Tourette Syndrome Subjects with moderate to severe TS will be enrolled in this treatment protocol Data from randomized double-blind placebo-controller trials of tics suggest that 60 points in the YGTSS total tic score is a reasonable estimate of the standard deviation of this outcome variable in the population of interest The investigators estimate that approximately 19 subjects will provide a desired power of 09 to detect a difference of 42 points in the mean 6-week change in YGTSS total tic score between the two treatment arms using a two-tailed t-test and a 5 level of significance
C Statistical evaluations The primary outcome measure is effective tic suppression as determined by the difference in Total Tic scores between treatment arms for levetiracetam and clonidine Secondary outcome measures include the Tic Impairment Score the Total YGTSS score and the CGI-I Data will be compared both as a change in absolute test score and as a percentage from baseline Unpaired Students t-tests will be used to compare treatment and placebo groups across all clinical variables at baseline A paired t-test with a 95 confidence interval will be used to compare changes in outcome measures from baseline to endpoint between the two treatment groups levetiracetam and clonidine regardless of treatment order Using a secondary assessment Analysis of Variance ANOVA with levels within respective classes containing subjects completing study 2 treatments and 2 periods the investigators will analyze each outcome measure as a two-period days 8 to 49 or 63 to 105 two-treatment two-sequence design with a test for the effects of treatment first or second period and treatment by period interaction To evaluate the effect of levetiracetam and clonidine on blood pressure pulse weight DuPaul ADHD scale CYBOCS CDI-S and MASC the investigators will conduct a series of repeated measures ANOVA to examine differences in each group across time Statistical significance for all analyses will be set at alpha005 for a two-tailed test This protocol format has been used effectively in a prior study of baclofen and levetiracetam
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
Procedures
i Screening visit Determination of diagnostic eligibility criteria medical history and complete physical examination evaluation of tic severity screening of females who have begun to menstruate with a urine pregnancy test familiarization with assessment procedures and obtaining informed consent The urine pregnancy test will be obtained in females over 12 years of age Parents will be told the results of these tests If the patient is uncomfortable with our telling the results of the pregnancy test to her parents then they may decide not to take part in this study
ii Baseline Visit Day 0 Evaluation prior to the run-in placebo phase will include weight heart rate blood pressure respiratory rate rating scales for tics the Yale Global Tic Severity Scale YGTSS and Childhood Global Impression-TS CGI-TS adverse effects the Pittsburgh Side-Effect Rating Scale obsessive-compulsive problems Child Yale-Brown Obsessive Compulsive Scale CY-BOCS attention deficit hyperactivity disorder DuPaul ADHD Rating Scale depression Child Depression Inventory- Short Version CDI-S anxiety the Multidimensional Anxiety Scale for Children MASC and episodic outbursts Rage Attack Rating Scale
iii Run-in Placebo Phase days 0-7 Immediately after the baseline visit the subject is started on placebo treatment for a one week period All subjects will receive 1 capsule twice a day capsules will be similar in appearance to that used in the drug treatment phase The Run-in phase has been added to eliminate subjects whose treatment outcome could be influenced by only a transient exacerbation of tics or by the exposure to non-pharmacologic treatment
a Post- Run in Period Evaluation day 8 Subjects will return for a re-evaluation of symptoms emphasis will be placed on rating scales for tics the Yale Global Tic Severity Scale YGTSS and Childhood Global Impression-TS CGI-TS and adverse effects the Pittsburgh Side-Effect Rating Scale If there is no tic improvement following the receipt of placebo the patient will move on to the treatment phase of the study In contrast if tic symptoms are reduced by more than 15 or significant side effects are reported all treatment will be discontinued and the subject will be withdrawn from the study
iv Treatment phases days 8 50 and days 65 107 A computer generated unequal randomized scheme will be used to assign patients to either levetiracetam or clonidine in the initial treatment phase Research Pharmacy at Johns Hopkins will be responsible for packaging levetiracetam supplied by UCB and clonidine purchased randomizing its allocation and distributing the medication Levetiracetam and clonidine will be repackaged in look-alike capsules with different dosage levels levetiracetam 250 milligrams mg or 500 mg and clonidine 005 mg or 01 mg Patients will receive a six week supply of medication at the first treatment phase visit day 8 and at the beginning of the second treatment phase day 63 A study physician Dr Harvey Singer will be responsible for changing medication dosage and monitoring side-effects A Safety Monitoring Board has been established to oversee medication use and monitor side-effects
1 Levetiracetam The starting dose of levetiracetam will be 10 mgkgday for one week administered as 5 mgkg twice a day BIDrounded to the closest unit of 250 mg If needed for tic suppression the dose will be increased weekly by 5-10 mgkilligramskgday The maximum dose will be 50 mgkgday administered as 25 mgkg BID with a maximum dose of 2500 milligrams per day For reference doses from 10 to 60 mgkgday of levetiracetam are currently being used in pediatric studies for the treatment of seizures and up to 2000 mg in TS children with a mean age of 12 years In any individual subject dose escalation may proceed more slowly or the dose may be reduced if necessary No changes in dosage will be made during the final week of both treatment phases
2 Clonidine The starting dose of clonidine will be 005mg BID for one week If needed for tic suppression the dose will be increased weekly by 005-01 mg The maximum dose will be 04 mg administered as 02 mg BID
iv Wash out phase Between the two treatment phases medication will be tapered over a ten day period Levetiracetam will be tapered at the end of each treatment phase by 5-10 mgkgday every third day The half life of levetiracetam is approximately 7-8 hours in healthy volunteers 5 8 hours in epileptic patients and about 10 hours in the elderly Clonidine will be tapered by 005 - 01 mg every third day Subjects will be off medication for 5 days before starting the second phase of the cross over study
v End of study drug taper At the completion of the second treatment phase medication will be tapered over a ten-day period reducing the medications in equal proportions every third day
vi Early stopping rules Subjects may be withdrawn from the study at any time at the discretion of the subject attending physician or investigator
1 The investigator decides the subject should be withdrawn This decision could be made because of an adverse effect or a failure to comply with the study protocol
2 The subject or hisher personal physician requests that the subject be withdrawn from the study
3 The subject for any reason requires treatment with another therapeutic agent that could conflict with the use of levetiracetam or clonidine
4 A Drug Safety Monitoring Board will monitor side effects and assist in determining whether a subject should be withdrawn from the trial Members of this board are full time Johns Hopkins Hospital faculty members and epilepsy fellows with experience in the use of levetiracetam The Board will have access to the randomization codes maintained by the statistician A quarterly update meeting will be scheduled for the Monitoring Board with topics to be reviewed including the number of subjects dosage schedules side effects and therapeutic responses Significant adverse events will be reported to the sponsor Union chimique belge Inc UCB Inc Johns Hopkins Joint Committee on Clinical Investigation JCCI and Food and Drug Administration FDA within 24 hours
vii Evaluations This is a 15 week study Telephone evaluations will be performed by the blinded Research Assistant on day 14 21 28 35 42 70 77 84 91 and 98 At each telephone session clinical response possible side effects drug compliance and medication adjustment will be discussed Subjects will be formally evaluated at 4 separate times including baseline day 0 at end of the run-in phase day 8 end of the first treatment phase day 49 at end of the drug wash out period day 63 and at end of the study day 105 Evaluations at each visit by the Research Assistant will include vital signs weight and an assessment of side effects using the Pittsburgh side effects scale The blinded outcome evaluator Dr Harvey Singer will administer and score the YGTSS CGI I DuPaul ADHD scale CY BOCS CDI S and MASC In addition at each visit a pill count will be done to assure compliance
C Outcomes Measures
i Yale Global Tic Severity Scale YGTSS The YGTSS is a semi-structured clinical interview designed to measure current tic severity Leckman et al 1989 This scale consists of the separate rating of severity for motor total motor 0 to 25 and vocal total vocal 0 to 25 tics Ratings are made along 5 discriminant dimensions on a scale of 0 to 5 for each including number frequency intensity complexity and interference Summation of these scores ie 0 to 50 provides a Total Tic Score TTS which will be the primary outcome measure The YGTSS also contains a separate ranking of impairment Tic Impairment Score or TIS with a maximum of 50 points based on the impact of the tic disorder on areas such as self esteem family life social acceptance and school scores Because the focus of this study is to evaluate the impact of levetiracetam and clonidine on tics and because the TIS may incorporate other components of TS the Total Tic Score TTS has been selected as the primary outcome measure
ii 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 ie 5 equals minimally worse 6 is much worse and 7 is very much worse
iii Child Yale-Brown Obsessive Compulsive Scale The severity of OCD will be evaluated using the Child Yale-Brown Obsessive Compulsive Scale 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 a Total score 0-40 The CY-BOCS is the most widely used instrument to assess the severity of obsessive-compulsive symptoms in research studies involving children It includes a checklist of specific obsessions and compulsions followed by examiner ratings of time spent interference distress resistance and control over the obsessions and compulsions assessed independently The CY-BOCS has well established psychometric properties
iv DuPaul ADHD Rating Scale The presence of ADHD symptoms will be assessed using the DSM-IV version of the ADHD rating scale developed by DuPaul This scale 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 This scale has been normed in large clinical and community samples and has excellent psychometric properties including a test-retest reliability over a 2-week period of 093 and significant correlations with direct observations of classroom behavior
v Child Depression Inventory-Short Version CDI-S Depression severity will be rated by using the Child Depression Inventory-Short Version CDI-S This 10 item scale takes about 5 minutes to complete It has excellent psychometric properties and is designed for repeated administrations over time
vi Multidimensional Anxiety Scale for Children MASC The childs anxiety will be followed using the multidimensional Anxiety Scale for Children MASC and is now considered the preferred instrument for rating childhood anxiety
vii Adverse effects Side effects will be assessed by an expanded 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
D Open Label Continuation
At the completion of the study the subject will be given the option of continuing either levetiracetam or clonidine in an open labeled fashion This will be enabled by having the subject seen by another physician who will have access to the study codes This physician will continue to follow the subject until the entire study is completed For members of the research team the treatment code will not be broken until all subjects have completed the protocol
IV Analytical Strategies A Inclusion of a Run-in phase The Run-in phase has been added to eliminate subjects whose treatment outcome could be influenced by a transient exacerbation of tics or by the exposure to non-pharmacologic treatment
B Power calculations As described this is a pilot randomized double-blind placebo-controlled cross-over project in which the investigators plan to enroll twenty patients between the ages of 7-19 years with Tourette Syndrome Subjects with moderate to severe TS will be enrolled in this treatment protocol Data from randomized double-blind placebo-controller trials of tics suggest that 60 points in the YGTSS total tic score is a reasonable estimate of the standard deviation of this outcome variable in the population of interest The investigators estimate that approximately 19 subjects will provide a desired power of 09 to detect a difference of 42 points in the mean 6-week change in YGTSS total tic score between the two treatment arms using a two-tailed t-test and a 5 level of significance
C Statistical evaluations The primary outcome measure is effective tic suppression as determined by the difference in Total Tic scores between treatment arms for levetiracetam and clonidine Secondary outcome measures include the Tic Impairment Score the Total YGTSS score and the CGI-I Data will be compared both as a change in absolute test score and as a percentage from baseline Unpaired Students t-tests will be used to compare treatment and placebo groups across all clinical variables at baseline A paired t-test with a 95 confidence interval will be used to compare changes in outcome measures from baseline to endpoint between the two treatment groups levetiracetam and clonidine regardless of treatment order Using a secondary assessment Analysis of Variance ANOVA with levels within respective classes containing subjects completing study 2 treatments and 2 periods the investigators will analyze each outcome measure as a two-period days 8 to 49 or 63 to 105 two-treatment two-sequence design with a test for the effects of treatment first or second period and treatment by period interaction To evaluate the effect of levetiracetam and clonidine on blood pressure pulse weight DuPaul ADHD scale CYBOCS CDI-S and MASC the investigators will conduct a series of repeated measures ANOVA to examine differences in each group across time Statistical significance for all analyses will be set at alpha005 for a two-tailed test This protocol format has been used effectively in a prior study of baclofen and levetiracetam
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None