Tourette Disorder, Tourette Syndrome
Conditions
Keywords
Tourette Syndrome, Tourette Disorder, Tics, Motor tics, Vocal tics, Intuniv, Guanfacine, Medication, Drug, Placebo, Child, Children, Adolescent
Brief summary
The goal of this pilot study is to obtain preliminary information on the tolerability and efficacy of extended release guanfacine (trade name Intuniv) in children with Tourette Disorder (TD, also called Tourette syndrome).
Detailed description
Guanfacine is commonly used for the treatment of tics in children with Tourette Disorder, but neither the immediate release compound nor the new extended release formulation have been evaluated for tics as a primary outcome. This pilot study is not designed to demonstrate efficacy of extended release guanfacine in the treatment of tics in children with TD. Rather, the goal of this trial is to determine whether extended release guanfacine warrants further study in a large scale trial. Immediate-release guanfacine is frequently used in children with TD, but dosing, time to effect and adverse effects with the new extended release guanfacine are unknown. The use of placebo in this trial reduces bias in the measurement of outcomes because it ensures blindness in the parent and clinician ratings. This is a three-site, investigator-initiated, randomized, double-blind, placebo-controlled, parallel-group study. Subjects who show a positive response to extended release guanfacine in the 8-week double-blind phase will continue on the the drug in an 8-week extension phase. Subjects who are randomly assigned to placebo and do not show improvement will be offered 8-weeks of open-label treatment with Intuniv.
Interventions
DRUGplacebo
Administered up to 8 weeks.
DRUGextended-release guanfacine (Intuniv)
1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks.
Sponsors
Icahn School of Medicine at Mount Sinai
University of South Florida
Shire
New York University
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Tourette Disorder or chronic motor or vocal tic disorder. * Between ages 6 yrs 0 mos and 17 years 0 months. * Weight \>/= 15 kg (33 lbs). * Ability to swallow pills whole.
Exclusion criteria
* IQ \< 80. * Positive pregnancy test. * Positive drug test. * Low blood pressure. * Prior history of hypersensitivity to guanfacine. * Prior failed treatment with an adequate trial of guanfacine in last 2 years. * Concurrent treatment with another psychoactive medication for tics, stimulant medication, or Habit Reversal therapy. * Medication for OCD, anxiety or depression will be allowed if dose is stable for 8 wks with no planned changes; SSRIs are allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Yale Global Tic Severity Scale (YGTSS) | 8 weeks | The YGTSS is a clinician-rated scale that begins with a systematic inquiry of tic symptoms in the preceding week. Current motor and phonic tics are rated separately according to number, frequency, intensity, complexity, and interference, each rated on 0 to 5 scale with higher scores indicating greater severity/worse outcome (Leckman et al. 1989). The YGTSS yields a total motor score (0-25), a total phonic score (0-25), a total tic score (sum of total motor and total phonic scores; 0-50), and an impairment score (0-50). Higher scores indicate greater severity/worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inactive Placebo placebo: Administered up to 8 weeks | 18 |
| Extended-release Guanfacine extended-release guanfacine (Intuniv): 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks | 16 |
| Total | 34 |
Baseline characteristics
| Characteristic | Inactive Placebo | Extended-release Guanfacine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 18 Participants | 16 Participants | 34 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.8 years STANDARD_DEVIATION 3.2 | 11.5 years STANDARD_DEVIATION 11 | 11.1 years STANDARD_DEVIATION 11.5 |
| Attention-Deficit/Hyperactivity Disorder Rating Scale (parent) | 17.5 units on a scale STANDARD_DEVIATION 13.65 | 19.7 units on a scale STANDARD_DEVIATION 12.29 | 18.5 units on a scale STANDARD_DEVIATION 18.4 |
| Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) | 10.5 units on a scale STANDARD_DEVIATION 11.43 | 9.6 units on a scale STANDARD_DEVIATION 10.41 | 10.1 units on a scale STANDARD_DEVIATION 15.5 |
| Clinical Global Impressions (CGI) Markedly ill | 6 Participants | 4 Participants | 10 Participants |
| Clinical Global Impressions (CGI) Moderately ill | 9 Participants | 12 Participants | 21 Participants |
| Clinical Global Impressions (CGI) Severely ill | 3 Participants | 0 Participants | 3 Participants |
| Disruptive Behavior Rating Scale (DBRS) | 5.6 units on a scale STANDARD_DEVIATION 7.37 | 8.8 units on a scale STANDARD_DEVIATION 6.59 | 7.1 units on a scale STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 13 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Premonitory Urge for Tics Scale (PUTS) | 20.9 units on a scale STANDARD_DEVIATION 8.18 | 19.8 units on a scale STANDARD_DEVIATION 5.39 | 20.4 units on a scale STANDARD_DEVIATION 9.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 16 Participants | 33 Participants |
| Rage Outbursts and Anger Rating Scale (ROARS) | 2.2 units on a scale STANDARD_DEVIATION 2.87 | 3.1 units on a scale STANDARD_DEVIATION 2.87 | 2.6 units on a scale STANDARD_DEVIATION 4.1 |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 23 Participants |
| Tanner stage Stage 1 or 2 | 11 Participants | 10 Participants | 21 Participants |
| Tanner stage Stage 3+ | 7 Participants | 6 Participants | 13 Participants |
| Tic Symptom Self-Report (TSSR) | 24.6 units on a scale STANDARD_DEVIATION 16.94 | 26.9 units on a scale STANDARD_DEVIATION 22.83 | 25.7 units on a scale STANDARD_DEVIATION 28.5 |
| Yale Global Tic Severity Scale (YGTSS) Impairment | 28.6 units on a scale STANDARD_DEVIATION 8.01 | 29.8 units on a scale STANDARD_DEVIATION 8.18 | 29.2 units on a scale STANDARD_DEVIATION 11.4 |
| Yale Global Tic Severity Scale (YGTSS) Total Motor score | 17.2 units on a scale STANDARD_DEVIATION 3.44 | 15.2 units on a scale STANDARD_DEVIATION 2.61 | 16.3 units on a scale STANDARD_DEVIATION 4.3 |
| Yale Global Tic Severity Scale (YGTSS) Total Phonic score | 10.4 units on a scale STANDARD_DEVIATION 6.73 | 11.1 units on a scale STANDARD_DEVIATION 6.13 | 10.7 units on a scale STANDARD_DEVIATION 9.1 |
| Yale Global Tic Severity Scale (YGTSS) Total Tic Score | 27.7 units on a scale STANDARD_DEVIATION 8.7 | 26.3 units on a scale STANDARD_DEVIATION 6.61 | 27.0 units on a scale STANDARD_DEVIATION 10.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 16 |
| other Total, other adverse events | 4 / 18 | 14 / 16 |
| serious Total, serious adverse events | 0 / 18 | 1 / 16 |
Outcome results
Primary
Yale Global Tic Severity Scale (YGTSS)
The YGTSS is a clinician-rated scale that begins with a systematic inquiry of tic symptoms in the preceding week. Current motor and phonic tics are rated separately according to number, frequency, intensity, complexity, and interference, each rated on 0 to 5 scale with higher scores indicating greater severity/worse outcome (Leckman et al. 1989). The YGTSS yields a total motor score (0-25), a total phonic score (0-25), a total tic score (sum of total motor and total phonic scores; 0-50), and an impairment score (0-50). Higher scores indicate greater severity/worse outcome.
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inactive Placebo | Yale Global Tic Severity Scale (YGTSS) | Total tic score | 24.72 units on a scale | Standard Deviation 10.54 |
| Inactive Placebo | Yale Global Tic Severity Scale (YGTSS) | Total Motor score | 15.00 units on a scale | Standard Deviation 5.87 |
| Inactive Placebo | Yale Global Tic Severity Scale (YGTSS) | Total Phonic Score | 9.72 units on a scale | Standard Deviation 6.43 |
| Inactive Placebo | Yale Global Tic Severity Scale (YGTSS) | Impairment | 23.44 units on a scale | Standard Deviation 11.51 |
| Extended-release Guanfacine | Yale Global Tic Severity Scale (YGTSS) | Impairment | 26.44 units on a scale | Standard Deviation 9.61 |
| Extended-release Guanfacine | Yale Global Tic Severity Scale (YGTSS) | Total tic score | 23.56 units on a scale | Standard Deviation 6.42 |
| Extended-release Guanfacine | Yale Global Tic Severity Scale (YGTSS) | Total Phonic Score | 10.63 units on a scale | Standard Deviation 5.49 |
| Extended-release Guanfacine | Yale Global Tic Severity Scale (YGTSS) | Total Motor score | 12.94 units on a scale | Standard Deviation 3.43 |