D-cycloserine Augmented Treatment for Youth With Tic Disorders

• ClinicalTrials.gov Identifier: NCT04357951
• Recruitment Status: Recruiting
• First Posted: April 22, 2020
• Last Update Posted: March 15, 2023
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

This pilot study aims evaluate the feasibility and initial efficacy of behavior therapy augmented by d-cycloserine (DCS) compared to behavior therapy augmented by placebo. After an initial assessment to determine eligibility, youth with TD will be randomly assigned to receive four sessions of behavior therapy augmented by either DCS or placebo. D-cycloserine is an FDA-approved antibiotic medication that has been shown to enhance extinction learning in several studies. The investigators' proof-of-concept work has found that a single session of DCS-augmented behavior therapy reduced the severity of tics targeted in treatment on the Hopkins Motor/Vocal Tic Scale (HM/VTS) compared to placebo-augmented behavior therapy. This highlights the exciting potential of combining DCS with behavior therapy to improve reductions in tic severity. However, prior to a large-scale clinical trial, it is essential to determine the feasibility and efficacy of augmenting behavior therapy with DCS over multiple treatment sessions.

Condition or disease	Intervention/treatment	Phase
Tourette Syndrome	Drug: d-cycloserine; Drug: Placebo pill; Behavioral: Behavior Therapy	Early Phase 1

Detailed Description:

Tourette's Disorder and Persistent Tic Disorders (collectively referred to as TD) are characterized by the presence of motor and/or vocal tics. For many youth with TD, the severity of tics results in considerable functional impairment and a poor quality of life. While historically managed with psychotropic medications, behavior therapy has demonstrated efficacy for reducing the severity of tics. However, only 50% of youth with TD exhibit a positive treatment response to behavior therapy, and many treatment responders continue to experience bothersome tics. Thus, there is a need to investigate strategies to improve therapeutic outcomes from behavior therapy for youth with TD.

This pilot study aims evaluate the feasibility and initial efficacy of behavior therapy augmented by d-cycloserine (DCS) compared to behavior therapy augmented by placebo. After an initial assessment to determine eligibility, youth with TD will be randomly assigned to receive four sessions of behavior therapy augmented by either DCS or placebo. D-cycloserine is an FDA-approved antibiotic medication that has been shown to enhance extinction learning in several studies. The investigators' proof-of-concept work has found that a single session of DCS-augmented behavior therapy reduced the severity of tics targeted in treatment on the Hopkins Motor/Vocal Tic Scale (HM/VTS) compared to placebo-augmented behavior therapy. This highlights the exciting potential of combining DCS with behavior therapy to improve reductions in tic severity. However, prior to a large-scale clinical trial, it is essential to determine the feasibility and efficacy of augmenting behavior therapy with DCS over multiple treatment sessions.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This trial will evaluate the feasibility and initial efficacy of behavior therapy augmented with d-cycloserine (DCS) compared to behavior therapy augmented with placebo.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Participants, therapists, investigators, and outcome assessors will all be masked to treatment assignment. Only the study coordinator will be aware of random assignment to treatment condition.
• Primary Purpose: Treatment
• Official Title: D-cycloserine Augmented Treatment: Enhancing Extinction Learning in Youth With Tic Disorders
• Estimated Study Start Date: April 15, 2023
• Estimated Primary Completion Date: March 2024
• Estimated Study Completion Date: September 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Behavior Therapy + DCS; Youth with TD will receive four, 2-hour long sessions of evidence-based behavior therapy delivered in an intensive format. Participants will arrive an hour early for each session to take the d-cycloserine pill prior to starting each session of behavior therapy. Participants, therapists, and outcome assessors will be masked to pill condition.	Drug: d-cycloserine; D-cycloserine is an FDA-approved antibiotic medication that has been shown to enhance extinction learning in several studies. It will be paired with 4 sessions of behavior therapy.; Behavioral: Behavior Therapy; All participants will receive 4 sessions of behavior therapy for tics (e.g., habit reversal training, comprehensive behavioral intervention for tics).
Active Comparator: Behavior Therapy + Placebo; Youth with TD will receive four, 2-hour long sessions of evidence-based behavior therapy delivered in an intensive format. Participants will arrive an hour early for each session to take the placebo pill prior to starting each session of behavior therapy. Participants, therapists, and outcome assessors will be masked to pill condition.	Drug: Placebo pill; A pill placebo serves as an active comparator. It will be paired with 4 sessions of behavior therapy.; Behavioral: Behavior Therapy; All participants will receive 4 sessions of behavior therapy for tics (e.g., habit reversal training, comprehensive behavioral intervention for tics).

Outcome Measures

Primary Outcome Measures :

1. Change in Hopkins Motor/Vocal Tic Scale (HM/VTS) score [ Time Frame: Pre-treatment (baseline) and 1 Week post-treatment ]
   Participants can nominate up to five motor and five vocal tics participants 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

• Ages Eligible for Study: 8 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 8-17 years
• Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for Tourette's Disorder, Persistent Motor Tic Disorder, or Persistent Vocal Tic Disorder
• Have moderate tic severity or greater as evidenced by a Yale Global Tic Severity Scale (YGTSS) total score greater than 13 (>9 for children with motor or vocal tics only)
• Be fluent in English

Exclusion Criteria:

• Current diagnosis of substance abuse/dependence
• Lifetime diagnosis of autism spectrum disorder, mania or psychosis
• History of a seizure disorder, kidney disease, or liver disease
• Four or more previous sessions of behavior therapy

Contacts and Locations

Contacts

Contact: Joseph McGuire, PhD; 443-287-7157; jfmcguire@jhmi.edu

Locations

United States, Maryland

Johns Hopkins University School of Medicine; Recruiting

Baltimore, Maryland, United States, 21205

Contact: Nicholas Myers, M.A 443-287-7157 coach@jhmi.edu

Principal Investigator: Joseph McGuire, PhD

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Joseph McGuire, PhD; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT04357951
• Other Study ID Numbers: IRB00210948
• First Posted: April 22, 2020
• Last Update Posted: March 15, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: This is a pilot study intended to demonstrate feasibility and test preliminary efficacy. The investigators do not plan to share individual participant data.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Johns Hopkins University:

habit reversal training; Comprehensive Behavioral Intervention for Tics; d-cycloserine; behavior therapy

Additional relevant MeSH terms:

Tourette Syndrome; Tic Disorders; Tics; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Cycloserine; Anti-Infective Agents, Urinary; Anti-Infective Agents; Renal Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action