Guanfacine in Children With Tic Disorders
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Placebo Comparator: Inactive placebo
|
Drug: placebo
Administered up to 8 weeks.
|
Experimental: Extended-release Guanfacine
|
Drug: extended-release guanfacine (Intuniv)
1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Yale Child Study Center | New Haven | Connecticut | United States | 06510 |
2 | University of South Florida | Tampa | Florida | United States | 33612 |
3 | Mount Sinai School of Medicine | New York | New York | United States | 10029 |
Sponsors and Collaborators
- Yale University
- Icahn School of Medicine at Mount Sinai
- University of South Florida
- Shire
- New York University
Investigators
- Study Director: Lawrence D Scahill, MSN, PhD, Emory University
- Principal Investigator: Barbara J Coffey, MD, MS, Icahn School of Medicine at Mount Sinai
- Principal Investigator: Tanya Murphy, MD, MS, University of South Florida
- Principal Investigator: Thomas Fernandez, MD, Yale University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1004006635
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Inactive Placebo | Extended-release Guanfacine |
---|---|---|
Arm/Group Description | placebo: Administered up to 8 weeks | extended-release guanfacine (Intuniv): 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks |
Period Title: Overall Study | ||
STARTED | 18 | 16 |
COMPLETED | 18 | 16 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Inactive Placebo | Extended-release Guanfacine | Total |
---|---|---|---|
Arm/Group Description | placebo: Administered up to 8 weeks | extended-release guanfacine (Intuniv): 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks | Total of all reporting groups |
Overall Participants | 18 | 16 | 34 |
Age (Count of Participants) | |||
<=18 years |
18
100%
|
16
100%
|
34
100%
|
Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
10.8
(3.2)
|
11.5
(11)
|
11.1
(11.5)
|
Sex: Female, Male (Count of Participants) | |||
Female |
6
33.3%
|
5
31.3%
|
11
32.4%
|
Male |
12
66.7%
|
11
68.8%
|
23
67.6%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
4
22.2%
|
3
18.8%
|
7
20.6%
|
Not Hispanic or Latino |
14
77.8%
|
13
81.3%
|
27
79.4%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
1
5.6%
|
0
0%
|
1
2.9%
|
White |
17
94.4%
|
16
100%
|
33
97.1%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Tanner stage (Count of Participants) | |||
Stage 1 or 2 |
11
61.1%
|
10
62.5%
|
21
61.8%
|
Stage 3+ |
7
38.9%
|
6
37.5%
|
13
38.2%
|
Yale Global Tic Severity Scale (YGTSS) (units on a scale) [Mean (Standard Deviation) ] | |||
Total Tic Score |
27.7
(8.7)
|
26.3
(6.61)
|
27.0
(10.9)
|
Total Motor score |
17.2
(3.44)
|
15.2
(2.61)
|
16.3
(4.3)
|
Total Phonic score |
10.4
(6.73)
|
11.1
(6.13)
|
10.7
(9.1)
|
Impairment |
28.6
(8.01)
|
29.8
(8.18)
|
29.2
(11.4)
|
Clinical Global Impressions (CGI) (Count of Participants) | |||
Moderately ill |
9
50%
|
12
75%
|
21
61.8%
|
Markedly ill |
6
33.3%
|
4
25%
|
10
29.4%
|
Severely ill |
3
16.7%
|
0
0%
|
3
8.8%
|
Tic Symptom Self-Report (TSSR) (units on a scale) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [units on a scale] |
24.6
(16.94)
|
26.9
(22.83)
|
25.7
(28.5)
|
Premonitory Urge for Tics Scale (PUTS) (units on a scale) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [units on a scale] |
20.9
(8.18)
|
19.8
(5.39)
|
20.4
(9.8)
|
Attention-Deficit/Hyperactivity Disorder Rating Scale (parent) (units on a scale) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [units on a scale] |
17.5
(13.65)
|
19.7
(12.29)
|
18.5
(18.4)
|
Disruptive Behavior Rating Scale (DBRS) (units on a scale) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [units on a scale] |
5.6
(7.37)
|
8.8
(6.59)
|
7.1
(9.9)
|
Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) (units on a scale) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [units on a scale] |
10.5
(11.43)
|
9.6
(10.41)
|
10.1
(15.5)
|
Rage Outbursts and Anger Rating Scale (ROARS) (units on a scale) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [units on a scale] |
2.2
(2.87)
|
3.1
(2.87)
|
2.6
(4.1)
|
Outcome Measures
Title | Yale Global Tic Severity Scale (YGTSS) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Inactive Placebo | Extended-release Guanfacine |
---|---|---|
Arm/Group Description | placebo: Administered up to 8 weeks. | extended-release guanfacine (Intuniv): 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks. |
Measure Participants | 18 | 16 |
Total tic score |
24.72
(10.54)
|
23.56
(6.42)
|
Total Motor score |
15.00
(5.87)
|
12.94
(3.43)
|
Total Phonic Score |
9.72
(6.43)
|
10.63
(5.49)
|
Impairment |
23.44
(11.51)
|
26.44
(9.61)
|
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Inactive Placebo | Extended-release Guanfacine | ||
Arm/Group Description | placebo: Administered up to 8 weeks | extended-release guanfacine (Intuniv): 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks | ||
All Cause Mortality |
||||
Inactive Placebo | Extended-release Guanfacine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/18 (0%) | 0/16 (0%) | ||
Serious Adverse Events |
||||
Inactive Placebo | Extended-release Guanfacine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/18 (0%) | 1/16 (6.3%) | ||
Psychiatric disorders | ||||
depressed mood | 0/18 (0%) | 0 | 1/16 (6.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Inactive Placebo | Extended-release Guanfacine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/18 (22.2%) | 14/16 (87.5%) | ||
Cardiac disorders | ||||
Hypotension | 1/18 (5.6%) | 3/16 (18.8%) | ||
Eye disorders | ||||
Other vision problems | 0/18 (0%) | 3/16 (18.8%) | ||
Gastrointestinal disorders | ||||
Stomach ache | 2/18 (11.1%) | 8/16 (50%) | ||
Constipation | 2/18 (11.1%) | 2/16 (12.5%) | ||
Nausea | 2/18 (11.1%) | 2/16 (12.5%) | ||
General disorders | ||||
Fatigue/tiredness | 3/18 (16.7%) | 14/16 (87.5%) | ||
Drowsiness | 3/18 (16.7%) | 12/16 (75%) | ||
Dry mouth | 4/18 (22.2%) | 10/16 (62.5%) | ||
Headache | 2/18 (11.1%) | 10/16 (62.5%) | ||
Decreased appetite | 3/18 (16.7%) | 8/16 (50%) | ||
Dizziness | 1/18 (5.6%) | 7/16 (43.8%) | ||
Emotional/tearful | 4/18 (22.2%) | 6/16 (37.5%) | ||
Daydreaming | 2/18 (11.1%) | 6/16 (37.5%) | ||
Trouble falling asleep | 4/18 (22.2%) | 5/16 (31.3%) | ||
Mid-sleep awakening | 3/18 (16.7%) | 2/16 (12.5%) | ||
Increased energy | 4/18 (22.2%) | 0/16 (0%) | ||
Increased appetite | 2/18 (11.1%) | 2/16 (12.5%) | ||
Psychiatric disorders | ||||
Depressed mood | 1/18 (5.6%) | 7/16 (43.8%) | ||
Anxiety | 4/18 (22.2%) | 2/16 (12.5%) | ||
Skin and subcutaneous tissue disorders | ||||
Skin rash | 0/18 (0%) | 3/16 (18.8%) | ||
Social circumstances | ||||
Irritability | 1/18 (5.6%) | 9/16 (56.3%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Tanya K. Murphy, MD, MS |
---|---|
Organization | University of South Florida |
Phone | 813-974-2201 |
tmurphy@health.usf.edu |
- 1004006635