DCS+HRT: Augmentation of Brief Habit Reversal Training With D-cycloserine or Placebo

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT02582515
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 22
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tourette Disorder; Chronic Tic Disorder	Drug: D-cycloserine; Drug: Placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Augmentation of Brief Habit Reversal Training With D-cycloserine or Placebo
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: D-cycloserine; Other Names: Habit Reversal Training
Placebo Comparator: 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.	Drug: Placebo; Other Names: Habit Reversal Training

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Semel Institute for Neuroscience and Human Behavior	Los Angeles	California	United States	90024

Sponsors and Collaborators

• University of California, Los Angeles

Investigators

• Principal Investigator: Joseph F McGuire, Ph.D., University of California, Los Angeles

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 24, 2016

More Information

Publications

None provided.

• Responsible Party: Joseph McGuire, Postdoctoral Fellow and Clinical Instructor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT02582515
• Other Study ID Numbers: UCLA_DCS+HRT
• First Posted: Oct 21, 2015
• Last Update Posted: Apr 25, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Joseph McGuire, Postdoctoral Fellow and Clinical Instructor, University of California, Los Angeles: d-cycloserine; comprehensive behavioral intervention for tics; habit reversal training
• Additional relevant MeSH terms: Tic Disorders; Tourette Syndrome; Disease; Cycloserine

Study Results

Participant Flow

Arm/Group Title	D-cycloserine + Habit Reversal Training	Placebo + Habit Reversal Training
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	9	11
Received Study Intervention	9	10
COMPLETED	9	10
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	D-cycloserine + Habit Reversal Training	Placebo + Habit Reversal Training	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	9	11	20
Age (Count of Participants)
<=18 years	9 100%	11 100%	20 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	3 27.3%	3 15%
Male	9 100%	8 72.7%	17 85%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 18.2%	2 10%
Not Hispanic or Latino	9 100%	9 81.8%	18 90%
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	3 33.3%	1 9.1%	4 20%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	6 66.7%	7 63.6%	13 65%
More than one race	0 0%	3 27.3%	3 15%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%	11 100%	20 100%
Yale Global Tic Severity Scale Total Tic Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.89 (6.05)	18.27 (3.85)	19.90 (5.16)

Outcome Measures

1. Primary Outcome

Title	Hopkins Motor/Vocal Tic Scale (HM/VTS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	D-cycloserine + Habit Reversal Training	Placebo + Habit Reversal Training
Arm/Group Description	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	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
Measure Participants	9	10
Mean (Standard Deviation) [score on a scale]	1.22 (0.62)	0.70 (0.54)

Adverse Events

Time Frame	Immediately after therapy session (Visit 2) and 1 week after therapy session (Visit 3)
Adverse Event Reporting Description	Adverse events were systematically assessed at Visits 2 and 3 using side effect review form derived from the Safety Monitoring Uniform Report Form (SMURF).
Arm/Group Title	D-cycloserine + Habit Reversal Training		Placebo + Habit Reversal Training
Arm/Group Description	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		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
All Cause Mortality
	D-cycloserine + Habit Reversal Training		Placebo + Habit Reversal Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/10 (0%)
Serious Adverse Events
	D-cycloserine + Habit Reversal Training		Placebo + Habit Reversal Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	D-cycloserine + Habit Reversal Training		Placebo + Habit Reversal Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)		0/10 (0%)
General disorders
Drowsiness	1/9 (11.1%)	1	0/10 (0%)	0
Difficulty Falling Asleep	1/9 (11.1%)	1	0/10 (0%)	0
Sore Throat	1/9 (11.1%)	1	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

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.