Chronic Tic Disorder, Tourette Disorder
Conditions
Keywords
d-cycloserine, comprehensive behavioral intervention for tics, habit reversal training
Brief summary
Expert reviews and practice parameter papers recommend behavior therapy as a first-line intervention for youth with chronic tic disorders (CTDs) with mild-to-moderate tic severity. Although behavior therapies like the Comprehensive Behavioral Intervention for Tics (CBIT) are efficacious in reducing tic symptom severity, only 50% of individuals exhibit a positive treatment response. Thus, there is a clear need to identify strategies to improve treatment response and/or accelerate therapeutic gains . The primary ingredient of CBIT is habit reversal training (HRT), which utilizes both extinction and associative learning. Psychosocial treatments relying on these learning mechanisms have demonstrated an enhanced and/or expedited therapeutic benefit when augmented with d-cycloserine (DCS). This feasibility study will examine the incremental efficacy of HRT+DCS over HRT+placebo for tics targeted with HRT. Eligibility criteria will parallel the child CBIT trial for generalizability and comparability, with the addition of DCS contraindications as exclusionary criteria. Parents and youth will complete a battery of clinical assessments to ascertain tic symptoms severity and co-occurring psychiatric conditions. Afterwards, participants will be randomly assigned to receive either HRT+DCS or HRT+placebo. Instead of a full course of HRT (8 sessions over 10 weeks), a more efficient Quick-Win/Fast-Fail trial design will be used that includes a truncated HRT protocol to provide results in a more timely fashion. As a result of this trial design, the primary outcome of this study will focus on the reduction of bothersome tic severity for those targeted in treatment rather than global severity reductions.
Detailed description
Expert reviews and practice parameter papers recommend behavior therapy as a first-line intervention for youth with chronic tic disorders (CTDs) with mild-to-moderate tic severity. Although behavior therapies like the Comprehensive Behavioral Intervention for Tics (CBIT) are efficacious in reducing tic symptom severity, only 50% of individuals exhibit a positive treatment response. Thus, there is a clear need to identify strategies to improve treatment response and/or accelerate therapeutic gains. The primary ingredient of CBIT is habit reversal training (HRT), which utilizes both extinction and associative learning. Psychosocial treatments relying on these learning mechanisms have demonstrated an enhanced and/or expedited therapeutic benefit when augmented with d-cycloserine (DCS). This feasibility study will examine the incremental efficacy of HRT+DCS over HRT+placebo for tics targeted with HRT. Eligibility criteria will parallel the child CBIT trial for generalizability and comparability, with the addition of DCS contraindications as exclusionary criteria. Parents and youth will complete a battery of clinical assessments to ascertain tic symptoms severity and co-occurring psychiatric conditions. Afterwards, participants will be randomly assigned to receive either HRT+DCS or HRT+placebo. Instead of a full course of HRT (8 sessions over 10 weeks), a more efficient Quick-Win/Fast-Fail trial design will be used that includes a truncated HRT protocol to provide results in a more timely fashion. As a result of this trial design, the primary outcome of this study will focus on the reduction of bothersome tic severity for those targeted in treatment rather than global severity reductions.
Interventions
DRUGD-cycloserine
DRUGPlacebo
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. ages 8 years to 17 years (inclusive); 2. meet diagnostic criteria for either Tourette Disorder or a Persistent Tic Disorder; 3. moderate tic severity or greater as evidenced by a Yale Global Tic Severity Scale (Leckman, Riddle, Hardin, & Ort, 1989) total score greater than 13 (\>9 for children with motor or vocal tics only); 4. be fluent in English; 5. be medication free or on a stable dose of a non-antipsychotic medication for 6 weeks with no planned changes.
Exclusion criteria
1. pregnant or breast feeding; 2. an unstable medical condition (e.g., a seizure disorder, kidney or liver disease); 3. current diagnosis of substance abuse/dependence; 4. lifetime diagnosis of schizophrenia, autism spectrum disorder, bipolar disorder, or psychosis; 5. evidence of a seizure disorder, kidney or liver disease, pregnant and/or breast feeding; 6. four or more previous sessions of HRT; or 7. currently taking an antipsychotic medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hopkins Motor/Vocal Tic Scale (HM/VTS) | Pre-treatment, One Week post-treatment | Participants can nominate up to five motor and five vocal tics they deem bothersome on the HM/VTS. Each bothersome tic is then rated by a clinician on a 5-point scale ranging from none (0) to severe (4). The individual tic scores are summed (minimum of 0 and maximum of 40) and averaged together to create an average tic severity score. Lower scores represent less tic severity, and higher scores indicate greater tic severity. The primary outcome will be the difference in the average score of the two bothersome tics on the HM/VTS that were targeted in treatment (range: 0-8). Change scores were calculated by subtracting the average of the two bothersome tics on the HM/VTS at post-treatment from the average of the two bothersome tics on the HM/VTS at the pre-treatment assessment. Positive scores indicate improvement/decrease in targeted tic severity, with negative scores indicating increase in targeted tic severity |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D-cycloserine + Habit Reversal Training Participants randomly assigned to the D-cycloserine (DCS) condition will receive a single dose of DCS immediately prior to a single session of habit reversal training. Participants will be evaluated 1 week later for improvement in tics targeted in the treatment session.
D-cycloserine | 9 |
| Placebo + Habit Reversal Training Participants randomly assigned to the placebo condition will receive a single dose of placebo immediately prior to a single session of habit reversal training. Participants will be evaluated 1 week later for improvement in tics targeted in the treatment session.
Placebo | 11 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo + Habit Reversal Training | Total | D-cycloserine + Habit Reversal Training |
|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 20 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 18 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 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 | 7 Participants | 13 Participants | 6 Participants |
| Region of Enrollment United States | 11 participants | 20 participants | 9 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 17 Participants | 9 Participants |
| Yale Global Tic Severity Scale Total Tic Score | 18.27 units on a scale STANDARD_DEVIATION 3.85 | 19.90 units on a scale STANDARD_DEVIATION 5.16 | 21.89 units on a scale STANDARD_DEVIATION 6.05 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 3 / 9 | 0 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Hopkins Motor/Vocal Tic Scale (HM/VTS)
Participants can nominate up to five motor and five vocal tics they deem bothersome on the HM/VTS. Each bothersome tic is then rated by a clinician on a 5-point scale ranging from none (0) to severe (4). The individual tic scores are summed (minimum of 0 and maximum of 40) and averaged together to create an average tic severity score. Lower scores represent less tic severity, and higher scores indicate greater tic severity. The primary outcome will be the difference in the average score of the two bothersome tics on the HM/VTS that were targeted in treatment (range: 0-8). Change scores were calculated by subtracting the average of the two bothersome tics on the HM/VTS at post-treatment from the average of the two bothersome tics on the HM/VTS at the pre-treatment assessment. Positive scores indicate improvement/decrease in targeted tic severity, with negative scores indicating increase in targeted tic severity
Time frame: Pre-treatment, One Week post-treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-cycloserine + Habit Reversal Training | Hopkins Motor/Vocal Tic Scale (HM/VTS) | 1.22 score on a scale | Standard Deviation 0.62 |
| Placebo + Habit Reversal Training | Hopkins Motor/Vocal Tic Scale (HM/VTS) | 0.70 score on a scale | Standard Deviation 0.54 |