D-cycloserine Augmented Treatment for Youth With Tic Disorders

D-cycloserine Augmented Treatment: Enhancing Extinction Learning in Youth With Tic Disorders

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 Overview

• Status: Withdrawn
• Conditions: Tourette Syndrome
• Intervention / Treatment: Drug: d-cycloserine; Behavioral: Behavior Therapy; Drug: Placebo pill

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 Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Joseph McGuire, PhD; Phone Number: 443-287-7157; Email: jfmcguire@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Behavioral: Behavior Therapy; All participants will receive 4 sessions of behavior therapy for tics (e.g., habit reversal training, comprehensive behavioral intervention for tics).; Drug: Placebo pill; A pill placebo serves as an active comparator. It will be paired with 4 sessions of behavior therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hopkins Motor/Vocal Tic Scale (HM/VTS) score	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.	Pre-treatment (baseline) and 1 Week post-treatment

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Joseph McGuire, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 15, 2023
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: habit reversal training; behavior therapy; Comprehensive Behavioral Intervention for Tics; d-cycloserine
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tourette Syndrome; Tic Disorders; Tics; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Cycloserine
• Other Study ID Numbers: IRB00210948

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• 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