Deep Brain Stimulation in Forel's H Field in Tourette's Syndrome

Bilateral Deep Brain Stimulation of Forel's H Field in Tourette's Syndrome: Prospective, Randomized, Crossover, Double-blind Study

Tourette's Syndrome (TS) is a neurodevelopmental disease characterized tics that start before the age of 18 years. About 5% of cases do not respond to drug treatment and can be classified as refractory and in these cases surgical treatment, with deep brain stimulation, appears as a therapeutic possibility, but with still conflicting results. Our hypothesis is that DBS in Forel's H Field could improve tourette's symptoms, neurological and psychiatric ones.

Study Overview

• Status: Active, not recruiting
• Conditions: Tourette Syndrome
• Intervention / Treatment: Device: Deep Brain Stimulation (DBS); Device: Sham Stimulation

Detailed Description

Sixteen patients with TS will be included in our protocol. The tics must have a negative influence in the quality of life of these patients. Patients will be submitted to a neuronavigation protocol for the precise location of the surgical target. After the surgery all patients will have the device turned ON for 6 months.

After the first 6 months participants will be randomly in two groups, one to stay with device ON or turned OFF at a period of 3 months. After that the groups will cross over for more 3 months. Clinical and video evaluations will be conducted before the surgery, at end of open fase, in the moment of cross over and at end of all.

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-000
      • University of Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 96 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Tourette's Syndrome diagnosis.
• Age equal to or above 14 years.
• Severe impairment of motor tics (Yale Global Tic Severity Scale ≥ 35/50).
• Patients who are refractory to drug treatment.
• Patients intellectually able to understand and sign the consent form.
• Possibility to adhere to research and periodic medical visits after surgery.

Exclusion Criteria:

• Inability to consent to your participation in the study.
• Patients with non-stabilized psychiatric comorbidities, such as anxiety and depression.
• Concomitant treatment with other experimental drugs.
• Women who are pregnant or breastfeeding.
• Patients undergoing previous neurosurgical procedures for the treatment of Tourette's Syndrome.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deep Brain Stimulation ON (DBS ON); The device will be turned ON	Device: Deep Brain Stimulation (DBS); The device will be ON
Sham Comparator: Deep Brain Stimulation OFF (DBS OFF); The device will be turned OFF	Device: Sham Stimulation; The device will be OFF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of change in the score of Yale Global Tic Severity Scale (YGTSS) pré and pós stimulation, comparing device On(active) and device OFF (sham) conditions.	Assess 5 items: number, frequency, intensity, complexity, interference. Each item is scored for phonic and motor tic symptom by the patient on a 0 to 5 numerical scale. The maximum possible score for these part is 50. Add to that the impairment score, which also has 50 as the maximum score. Total Yale Global Tic Severity Scale Score (Total Tic Severity Score + Impairment). The maximum possible score for the total scale is 100. Lower scores of YGTSS represents less tics.	month 0: baseline; month 8: end off open label phase. All patients had de device ON for 6 months. month 11: after 3 months of device ON or OFF. month 14: after 3 months of device in opposite situation at evaluation at month 11.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in psychiatric symptoms - Anxiety	To assess the influence of deep brain stimulation on anxiety by comparing specific scales for the quantitative assessment of this symptom. The scale used is Beck Anxiety Inventory (BAI), a self-report measure of anxiety and total score is calculated by finding the sum of the 21 items.	month 0: baseline; month 8: end off open label phase. All patients had de device ON for 6 months. month 11: after 3 months of device ON or OFF. month 14: after 3 months of device in opposite situation at evaluation at month 11.
Change in Quality of Life	Percent change in the score of Gilles de la Tourette Syndrome - Quality of Life scale (GTS-QOL) comparing baseline, device On and device OFF conditions. The GTS-QOL consisted of 27 items and four subscales (psychological, physical, obsessive compulsive and cognitive. Each item is rated across five response options: 'Never', 'Rarely', 'Sometimes', 'Often', 'Always'.	month 0: baseline; month 8: end off open label phase. All patients had de device ON for 6 months. month 11: after 3 months of device ON or OFF. month 14: after 3 months of device in opposite situation at evaluation at month 11.
Change in psychiatric symptom - Depression	To assess the influence of deep brain stimulation on depression by comparing specific scales for the quantitative assessment of this symptoms. The scale used is the Beck Depression Inventory (BDI), a 21 item self-rated scale that evaluates key symptoms of depression.	month 0: baseline; month 8: end off open label phase. All patients had de device ON for 6 months. month 11: after 3 months of device ON or OFF. month 14: after 3 months of device in opposite situation at evaluation at month 11.
Change in psychiatric symptom - obsessive-compulsive disorder	To assess the influence of deep brain stimulation on obsessive-compulsive disorder (OCD) by comparing specific scales for the quantitative assessment of this symptoms. The scale used is Yale-Brown Obsessive Compulsive Scale (Y-BOCS), a widely used clinician-rated measure for assessing obsessive-compulsive symptoms.	month 0: baseline; month 8: end off open label phase. All patients had de device ON for 6 months. month 11: after 3 months of device ON or OFF. month 14: after 3 months of device in opposite situation at evaluation at month 11.
Change in psychiatric symptom - attention deficit hyperactivity disorder	To assess the influence of deep brain stimulation on attention deficit hyperactivity disorder (ADHD) by comparing specific scales for the quantitative assessment of this symptom.The scale used is Adult Self-Report Scale (ASRS-18).	month 0: baseline; month 8: end off open label phase. All patients had de device ON for 6 months. month 11: after 3 months of device ON or OFF. month 14: after 3 months of device in opposite situation at evaluation at month 11.
assessment of structural connectivity patterns	To assess the variation in the clinical response depending on the pattern of structural connectivity presented by accessing imaging tests of white matter tracts potentially stimulated through ECP targeting the Forel H field.	month 0: baseline; month 8: end off open label phase. All patients had de device ON for 6 months. month 11: after 3 months of device ON or OFF. month 14: after 3 months of device in opposite situation at evaluation at month 11.

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Rubens G Cury, MD PhD, University of Sao Paulo General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2019
• Primary Completion (Anticipated): December 27, 2022
• Study Completion (Anticipated): June 27, 2023

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation; Tourette Syndrome; DBS
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: 3.158.435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No