Neural Correlates of Sensory Phenomena in Tourette Syndrome

• ClinicalTrials.gov Identifier: NCT03914664
• Recruitment Status: Recruiting
• First Posted: April 16, 2019
• Last Update Posted: July 1, 2022
• Sponsor: Vanderbilt University Medical Center
• Information provided by (Responsible Party): David Isaacs, Vanderbilt University Medical Center

Study Description

Brief Summary:

The primary aim of this study is to identify neural correlates of sensory phenomena in adults with Tourette syndrome (TS). Adult patients with TS will be recruited 1) to complete a standardized clinical symptom assessment battery and 2) to undergo monitoring with video-electroencephalogram (EEG) during tactile and auditory stimuli paradigms, as well as in a resting state paradigm.

Condition or disease	Intervention/treatment
Tourette Syndrome; Sensory Disorders; Hypersensitivity; Tics	Diagnostic Test: Electroencephalogram (EEG) testing procedure; Diagnostic Test: Autonomic function testing procedure

Detailed Description:

Tourette syndrome (TS) is a neurodevelopmental disorder affecting 1% of school-aged children; one-third of patients suffer persistent tics into adulthood. Diagnostic criteria rely solely on motor symptoms, but sensory phenomena are a nearly universal feature, manifesting as 1) premonitory urges (PUs) and 2) sensory hypersensitivity. 1) Ninety percent of patients perceive unpleasant premonitory bodily urges preceding tic expression, and 60% find these more distressing than tics themselves. As PUs and tics are clinically paired, one would expect tight symptom severity correlation; however, published results are conflicting. Imaging studies reveal the likely role of a widespread sensory processing network in PU formation, but much ambiguity surrounds the precise neural substrates of PUs. 2) In addition to PUs, 80% of TS patients report heightened awareness of internal and external stimuli. Scant research has been devoted to this aspect of TS, but one small series found this sensory hypersensitivity to be independent of both PU and tic severity, delineating it as a distinct facet of the syndrome. Despite their ubiquity and detrimental impact on quality of life, sensory phenomena in TS remain poorly understood: the clinical relationship with tics is unclear, the pathophysiologic mechanisms are imprecisely characterized, and the treatment is non-existent. Network oscillations, captured in real-time with EEG, are a promising means of addressing this crucial knowledge gap.

Part 1. Clinical Variables and Scales - Adult TS patients will be recruited to complete a battery of validated clinical scales, providing a comprehensive phenotype. The scales include the following: Yale Global Tic Severity Scale (YGTSS); Dimensional Obsessive-Compulsive Scale (DOCS); Adult ADHD Self-Report Screening Scale for DSM-V; Generalized Anxiety Disorder 7 (GAD-7); Patient Health Questionnaire 9 (PHQ-9); Premonitory Urge to Tic Scale (PUTS); Sensory Gating Inventory (SGI); Sensory Perception Quotient (SPQ); and GTS-Quality of Life (GTS-QOL) Rating Scale. Patients with previously diagnosed autism spectrum disorder, developmental delay, cerebral palsy, other significant neurologic disease, schizophrenia, or psychotic disorders will be excluded, in order to lessen potentially confounding factors. Patients with obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), anxiety, and/or depression will be permitted, given that these diagnoses are widely prevalent in the adult TS population. Age-matched, healthy-controls (HCs) will be recruited to complete the mood and sensory instruments. All study procedures will be completed during a single testing session. Medical and neurologic history, family history, substance use history, developmental history, and current and past psychotropic pharmacotherapies, will be reviewed.

Part 2. EEG Testing - Each participant will undergo a single-session EEG paradigm consisting of somatosensory and auditory event-related potentials (ERP), as well as a resting state condition. The somatosensory stimulus consists of a non-painful stimulus to the arm, and the auditory stimulus consists of a non-painful sound delivered through headphones. The entire recording session will take approximately 1-1.5 hours. Participants will be video-recorded, to allow for subsequent identification of tics. Participants will also be monitored with electrodes to monitor heart rate and sweating.

Study Design

• Study Type: Observational
• Estimated Enrollment: 50 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Neural Correlates of Sensory Phenomena in Tourette Syndrome
• Actual Study Start Date: July 20, 2021
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: December 2024

Groups and Cohorts

Group/Cohort	Intervention/treatment
Tourette Syndrome; Adults (>18 years of age) with diagnosis of Tourette syndrome	Diagnostic Test: Electroencephalogram (EEG) testing procedure; EEG testing procedure, comprised of somatosensory and auditory event-related potential paradigms, as well as resting state EEG; Diagnostic Test: Autonomic function testing procedure; Autonomic function testing procedure, comprised of electrocardiogram (EKG) electrodes to determine heart rate variability and electrodermal activity (EDA) electrodes
Healthy Control; Adults who are generally healthy with no known neurologic or psychiatric diagnoses	Diagnostic Test: Electroencephalogram (EEG) testing procedure; EEG testing procedure, comprised of somatosensory and auditory event-related potential paradigms, as well as resting state EEG; Diagnostic Test: Autonomic function testing procedure; Autonomic function testing procedure, comprised of electrocardiogram (EKG) electrodes to determine heart rate variability and electrodermal activity (EDA) electrodes

Outcome Measures

Primary Outcome Measures :

1. Network oscillations in response to sensory stimuli [ Time Frame: Baseline ]
   Neural activity captured on EEG can be spectrally decomposed into various frequency constituencies. Neural activity in the gamma frequency range, so-called gamma band oscillations (GBOs), are associated with sensory processing and integration and are postulated to underlie sensory phenomena in TS.
2. Heart rate variability [ Time Frame: Baseline ]
   Change beat-to-beat variability in heart rate
3. Electrodermal activity in response to sensory stimuli [ Time Frame: Baseline ]
   Sweat response changes within 1-3 seconds of non-aversive sensory stimulus

Secondary Outcome Measures :

1. Premonitory Urge to Tic Scale (PUTS) [ Time Frame: Within 1 month of baseline ]
   Validated self-report questionnaire comprised of 9 items assessing character and severity of premonitory urges. Scale range: 9 (least affected) - 36 (most affected)
2. Yale Global Tic Severity Scale (YGTSS) [ Time Frame: Within 1 month of baseline ]
   Validated, gold-standard clinician-administered tic assessment scale, comprised of 11 items. Scale range: 0 (best) - 100 (worst)
3. Dimensional Obsessive Compulsive Scale (DOCS) [ Time Frame: Within 1 month of baseline ]
   Validated self-report questionnaire assessing severity of obsessive and compulsive symptoms, comprised of 20 items. Scale range 0 (least affected) - 80 (most affected)
4. Adult ADHD Self-Report Screening Scale [ Time Frame: Within 1 month of baseline ]
   Validated self-report scale, developed since release of Diagnostic and Statistical Manual-V, comprised of 6 items. Scale range 0 (least affected) - 24 (most affected)
5. Generalized Anxiety Disorder 7 (GAD-7) [ Time Frame: Within 1 month of baseline ]
   Validated self-report scale assessing presence and extent of anxiety, comprised of 7 items. Scale range 0 (least affected) - 21 (most affected)
6. Patient Health Questionnaire 9 (PHQ-9) [ Time Frame: Within 1 month of baseline ]
   Validated self-report scale assessing presence and extent of depression, comprised of 9 items. Scale range 0 (least affected) - 27 (most affected)
7. Sensory Gating Inventory (SGI) [ Time Frame: Within 1 month of baseline ]
   Validated self-report questionnaire assessing sensory hypo- or hyper-sensitivity, comprised of 36 items. The 4 sub-scales include Perceptual Modulation, Distractability, Over-Inclusion, and Fatigue and Stress Vulnerability. Total scale range 0 (least affected) - 180 (most affected)
8. Sensory Perception Quotient (SPQ) [ Time Frame: Within 1 month of baseline ]
   Validated self-report questionnaire assessing sensory hypo- or hyper-sensitivity, comprised of 35 items. Scale range 0 (highest sensory sensitivity) - 105 (lowest sensory sensitivity).
9. Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) [ Time Frame: Within 1 month of baseline ]
   Validated self-report questionnaire assessing health-related quality of life for patients with Tourette syndrome, comprised of 27 items. Scale range 0 (best quality of life) - 108 (worst quality of life)
10. Patient Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment [ Time Frame: Within 1 month of baseline ]
    Validated self-report questionnaire to measures sleep-related impairments, consisting of 8 items. Scale range 0 - 100 (t-score scaled with lower values indicating less impairment).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

The two groups of participants will include 1) patients with Tourette syndrome and 2) healthy controls.

Criteria

Inclusion Criteria:

• Diagnosis of Tourette syndrome
• fluent in English
• Age greater than or equal to 18 years

Exclusion Criteria:

• Prior diagnosis of autism spectrum disorder, developmental delay, cerebral palsy, other significant neurologic disease, schizophrenia, or psychotic disorders
• Previously diagnosed hearing or tactile impairment
• Current use of benzodiazepines (e.g. Clonazepam, Diazepam, Alprazolam) or anti-seizure medications (e.g. Topiramate, Lamotrigine)

Contacts and Locations

Contacts

Contact: David A Isaacs, MD; 615-875-7394; david.a.isaacs@vumc.org

Contact: Michelle R Eckland, BS; 615-875-7394; michelle.r.eckland.1@vumc.org

Locations

United States, Tennessee

Vanderbilt University Medical Center; Recruiting

Nashville, Tennessee, United States, 37232-5400

Contact: Michelle R Eckland, BS 615-875-7394 michelle.r.eckland.1@vumc.org

Principal Investigator: David A Isaacs, MD

Sub-Investigator: Heather Riordan, MD

Sponsors and Collaborators

Vanderbilt University Medical Center

More Information

• Responsible Party: David Isaacs, Assistant Professor, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT03914664
• Other Study ID Numbers: NCoSPTS
• First Posted: April 16, 2019
• Last Update Posted: July 1, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified clinical variables and EEG data metrics may be shared with other researchers.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: The above information will be available for sharing within 6 months of publication.
• Access Criteria: Researchers wishing to access the above information should contact the investigative team and provide: 1) hypothesis-driven scientific question for which the data will be analyzed and 2) proposed methods for responsibly analyzing the data.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Tourette Syndrome; Sensation Disorders; Hypersensitivity; Syndrome; Disease; Pathologic Processes; Immune System Diseases; 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; Neurodevelopmental Disorders; Mental Disorders; Neurologic Manifestations