D-cycloserine Augmented Treatment for Youth With Tic Disorders

NCT04357951 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: IRB00210948
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Tourette Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Behavior Therapy + DCS

EXPERIMENTAL

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; Behavioral: Behavior Therapy

Behavior Therapy + Placebo

ACTIVE COMPARATOR

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; Behavioral: Behavior Therapy

Interventions

d-cycloserine DRUG

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.

Behavior Therapy + DCS

Placebo pill DRUG

A pill placebo serves as an active comparator. It will be paired with 4 sessions of behavior therapy.

Behavior Therapy + Placebo

Behavior Therapy BEHAVIORAL

All participants will receive 4 sessions of behavior therapy for tics (e.g., habit reversal training, comprehensive behavioral intervention for tics).

Behavior Therapy + DCS; Behavior Therapy + Placebo

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Tourette Syndrome

Interventions

Cycloserine; Behavior Therapy

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tic Disorders; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Joseph McGuire, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial will evaluate the feasibility and initial efficacy of behavior therapy augmented with d-cycloserine (DCS) compared to behavior therapy augmented with placebo.

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 22, 2020
• Study Start: April 15, 2023
• Primary Completion: March 1, 2024
• Study Completion: September 1, 2024
• Last Updated: April 14, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)