Guanfacine in Children With Tic Disorders

Sponsor
Yale University (Other)
Overall Status
Completed
CT.gov ID
NCT01547000
Collaborator
Icahn School of Medicine at Mount Sinai (Other), University of South Florida (Other), Shire (Industry), New York University (Other)
34
3
2
56
11.3
0.2

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
  • Drug: placebo
  • Drug: extended-release guanfacine (Intuniv)
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

Study Type:
Interventional
Actual Enrollment :
34 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Guanfacine in Children With Tic Disorders: A Multi-site Study
Study Start Date :
Apr 1, 2012
Actual Primary Completion Date :
Dec 1, 2016
Actual Study Completion Date :
Dec 1, 2016

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:
  • Intuniv
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    Ages Eligible for Study:
    6 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    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.
    Responsible Party:
    Yale University
    ClinicalTrials.gov Identifier:
    NCT01547000
    Other Study ID Numbers:
    • 1004006635
    First Posted:
    Mar 7, 2012
    Last Update Posted:
    Aug 13, 2021
    Last Verified:
    Aug 1, 2021

    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

    1. Primary Outcome
    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

    We are limited by the small size of this subgroup to determine whether children with comorbid CTD and ADHD might have a significant response to extended-release guanfacine, both with regard to tics and ADHD symptoms.

    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
    Email tmurphy@health.usf.edu
    Responsible Party:
    Yale University
    ClinicalTrials.gov Identifier:
    NCT01547000
    Other Study ID Numbers:
    • 1004006635
    First Posted:
    Mar 7, 2012
    Last Update Posted:
    Aug 13, 2021
    Last Verified:
    Aug 1, 2021