NCT00529308

Brief Summary

This study will evaluate the clinical efficacy of 1 Hz repetitive transcranial magnetic stimulation (rTMS) applied to the supplementary motor area (SMA) in Tourette's Syndrome (TS) patients who have not fully responded to conventional therapies. The investigators will collect TMS measures of motor cortex excitability to test whether rTMS restores normal levels of intracortical inhibition found to be deficient in TS. The investigators will administer neuropsychological tests to demonstrate that SMA targeted rTMS can be administered safely without significant impairments of cognitive or motor functioning. The investigators hypothesize that:

  1. 1.Compared to sham (placebo), active rTMS will improve symptoms of TS as assessed with the Yale Global Tic Severity Scale (Y-GTSS) and Clinical Global Impression (CGI).
  2. 2.Active (but not sham) rTMS will normalize levels of motor cortex excitability, as reflected by increased intracortical inhibition, motor threshold, and cortical silent period, and by decreased intracortical facilitation, relative to pre-treatment baseline.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2007

Typical duration for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2007

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 13, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 14, 2007

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2011

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

February 15, 2013

Completed
Last Updated

February 21, 2019

Status Verified

February 1, 2019

Enrollment Period

4 years

First QC Date

September 13, 2007

Results QC Date

November 13, 2012

Last Update Submit

February 4, 2019

Conditions

Keywords

TouretteTourette's

Outcome Measures

Primary Outcomes (5)

  • Yale Global Tic Severity Scale (Y-GTSS)

    Y-GTSS is a clinician-rated scale used to assess tic severity. Motor and phonic tics are rated separately from 0 to 5 on several scales including number, frequency, intensity, complexity, and interference. Thus Motor and Phonic Tic scores can range from 0 to 25; the combined Total Tic Score ranges from 0 to 50. There is also an Impairment score that rates the overall burden due to tics. The Impairment scale yields a single score from 0 to 50 with higher scores indicating higher levels of overall impairment associated with tics.

    3 weeks

  • Motor Cortex Excitability Normalization-Right Motor Threshold

    Motor Threshold (MT) is thought to be a measure of membrane excitability in pyramidal neurons. MT is defined as the minimum magnetic flux needed to elicit a threshold EMG response (50 µV in peak to peak amplitude) in a resting target muscle in 5 out of 10 trials using single pulse TMS administered to the contralateral primary motor cortex. MT for both right and left hand are determined, and the lowest is used to select the intensity for rTMS.

    3 weeks

  • Number of Patients With "Much Improved or Very Much Improved" on Clinical Global Impression-Improvement (CGI) Scale

    The CGI-I is a clinician-rated scales that have been used in clinical trials for over 25 years. Clinicians rate patient improvement compared to baseline. By convention, 4 = No Change; scores of 5, 6, and 7 move in the direction of worsening; scores of 3, 2, and 1 correspond to "Minimal Improvement," "Much Improved" or "Very Much Improved," respectively. CGI-I ratings of "Much" or "Very Much Improved" at post-treatment are used to identify treatment responders.

    3 weeks

  • Motor Cortex Excitability Normalization-Left Motor Threshold

    Motor Threshold (MT) is thought to be a measure of membrane excitability in pyramidal neurons. MT is defined as the minimum magnetic flux needed to elicit a threshold EMG response (50 µV in peak to peak amplitude) in a resting target muscle in 5 out of 10 trials using single pulse TMS administered to the contralateral primary motor cortex. MT for both right and left hand are determined, and the lowest is used to select the intensity for rTMS.

    3 weeks

  • Number of Patients With "Improved or Minimally Improved" in Clinical Global Impression-Improvement (CGI) Scale

    The CGI-I is a clinician-rated scales that have been used in clinical trials for over 25 years. Clinicians rate patient improvement compared to baseline. By convention, 4 = No Change; scores of 5, 6, and 7 move in the direction of worsening; scores of 3, 2, and 1 correspond to "Minimal Improvement," "Much Improved" or "Very Much Improved," respectively. CGI-I ratings of "Much" or "Very Much Improved" at post-treatment are used to identify treatment responders.

    3 weeks

Study Arms (2)

Active

ACTIVE COMPARATOR
Device: Transcranial Magnetic Stimulation (active)

Sham

SHAM COMPARATOR
Device: Transcranial Magnetic Stimulation (sham)

Interventions

Magstim Rapid2 stimulator with Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.

Also known as: Magstim Rapid2
Active

Magstim Rapid2 stimulator with Sham Air Film Coil at 110% motor threshold at 1Hz for 30 minutes.

Also known as: Magstim Rapid2
Sham

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Primary diagnosis of Tourette's Syndrome, as confirmed by the DSM-IV-TR criteria
  • Residual TS symptoms, defined as a total Y-GTSS total motor tic or phonic tic score \> 20, despite treatment with an adequate trial of medications (defined as a failure to respond to a trial of commonly used medications for TS such as clonidine, guanfacine, or neuroleptic medications, given at recommended dosage and duration based on the clinician's judgment)
  • Persistent high level of tic severity for 4 months despite efforts to control the tics using medications, or the presence of self injurious tics
  • Duration of the index episode of at least a year
  • Individuals who cannot tolerate medications of class and dose at the specified duration as described above will also be included
  • Patients currently on medication must be at the same stable dose(s) for one month prior to enrollment and be willing to continue at the same dose(s) through the duration of the study

You may not qualify if:

  • Individuals diagnosed with major depressive disorder (current) of moderate or severe intensity (CGI ≥ 4), bipolar disorder (lifetime), any psychotic disorder (lifetime), or an Axis II personality disorder; with a history of substance abuse or dependence within the past year (except nicotine and caffeine); or at significant acute suicide risk will be excluded
  • Individuals with a clinically defined neurological disorder, with an increased risk of seizure for any reason, with a history of treatment with TMS, deep brain stimulation for any disorder will be excluded
  • Patients with cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed will be excluded
  • Current use of any investigational drug, any medications with proconvulsive action, such as bupropion, maprotiline, tricyclic antidepressant, clomipramine, classical antipsychotics, and daily use of any medications with a known inhibitory effect on cortical excitability measures (e.g., anticonvulsants, standing doses of benzodiazepines, sedative/hypnotics, and atypical antipsychotics) will not be permitted
  • If participating in psychotherapy, patients must have been in stable treatment for at least three months prior to entry into the study, with no anticipation of change in frequency therapeutic sessions, or the therapeutic focus over the duration of the TMS trial
  • Finally, current significant laboratory abnormality, known or suspected pregnancy, women who are breast-feeding or women of childbearing potential not using a medically accepted form of contraception when engaging in sexual intercourse will also be excluded.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

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Related Links

MeSH Terms

Conditions

Tourette Syndrome

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Basal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTic DisordersMovement DisordersHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeurodevelopmental DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Results Point of Contact

Title
Dr. Angeli Landeros-Weisenberger
Organization
Yale University

Study Officials

  • Antonio Mantovani, MD

    New York State Psychiatric Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

September 13, 2007

First Posted

September 14, 2007

Study Start

July 1, 2007

Primary Completion

July 1, 2011

Study Completion

July 1, 2011

Last Updated

February 21, 2019

Results First Posted

February 15, 2013

Record last verified: 2019-02

Locations