rTMS Bimodal Treatment For Tinnitus: A Pilot Study

Study Overview
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Brief Summary
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Repetitive Transcranial Magnetic Stimulation (rTMS) is a novel brain stimulation technique that uses pulsating magnetic fields to stimulate underlying neurons in the cerebral cortex. The investigators propose an open-label pilot study investigating the effectiveness of rTMS in the treatment of tinnitus stimulation of the left dorsolateral prefrontal cortex (DLPFC), an area known to be important for mood and attention, along with stimulation of the left temporoparietal cortex (TPC). This is a feasibility pilot study.

Detailed Description
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Converging data implicate structures of the brain that are important for mood and attention as playing a role in the maintenance of tinnitus; suggesting an alternative rTMS treatment approach that targets these structures. A growing number of studies demonstrate involvement of the prefrontal cortex in the generation and maintenance of tinnitus. rTMS stimulation in the dorsolateral prefrontal cortex in association with stimulation in the temporoparietal cortex has been shown to increase the durability of the TPC stimulation. The independent effect of rTMS stimulation to the DLPFC is not known. Studies in depression suggest that increasing the intensity and duration of stimulation has beneficial treatment effects. However, the field is new and more work is needed to assess the effectiveness of this treatment, predictors and correlates of response, and safety. Recent exciting work in schizophrenia used a bimodal (DLPFC and TPC) treatment approach in pharmacologically non-responsive patients. The study used high-frequency stimulation to the left DLPFC and low-frequency stimulation to the left TPC. Bimodal rTMS stimulation of left DLPFC and left TPC induced clinical improvement in pharmacologically non-responsive schizophrenia patients and may have improved their short-term verbal memories.57

Official Title
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rTMS Bimodal Treatment For Patients With Subjective Idiopathic Tinnitus: A Pilot Study

Conditions
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Tinnitus

Intervention / Treatment
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* Device: Bimodal rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be between the ages of 18 and 60 years. Subjective, idiopathic, troublesome, unilateral or bilateral, non-pulsatile tinnitus of ≥ 2 month's duration but no greater than 5 year's duration. Bothersome Tinnitus according to Tinnitus Handicap Inventory score. Must be able to understand, speak, read and write English proficiently Able to provide informed consent Women who are of childbearing potential must agree to use a medically acceptable form of birth control and must have a negative urine pregnancy test at screening Exclusion Criteria: •• Patients with tinnitus related to cochlear implantation, retrocochlear lesion, or other known anatomic/structural lesions of the ear and temporal bone. Patients with a history of stapedectomy and insertion of implant will be excluded. Hypersensitive to noises (hyperacusis) Patients with history of head injury with 15 minutes or more loss of consciousness or required medical treatment. Patients with cardiac pacemakers; intracardiac lines; implanted medication pumps; implanted electrodes in the brain; other implanted electrical or magnetic medical devices; or other intracranial metal objects or shrapnel, with the exception of dental fillings. Patients with additional significant neurological disorders including increased intracranial pressure, brain mass, epileptic seizures (or family history of epileptic seizures), history of stroke, transient ischemic attack within 2 years, cerebral aneurysm, Huntington's chorea or multiple sclerosis. Patients with an acute or unstable medical condition including all patients with any significant heart disease, pneumonia, uncontrolled hypertension, or other disorders which would require stabilization prior to initiation of transcranial magnetic stimulation. Active alcohol and/or drug dependence or history of alcohol and/or drug dependence within the last year. Patients with moderate to severe clinical depression as evidenced by a score of 15 or greater on the PHQ-9. Patients who, in the opinion of the psychiatric sub-investigator, demonstrate moderate to severe depressive symptoms according to DSM-IV-TR criteria for Major Depressive Disorder. Patients with psychiatric illness or trauma which would prohibit participation in the study. Patients with active psychotic symptoms or a history of psychotic disorder Female patients of child-bearing potential, unless sterilized or using an appropriate form of birth control acceptable to the research team. Currently breastfeeding Currently pregnant Patients will be excluded if a motor threshold cannot be elicited, Patients whose ability to give informed consent is in question Undiagnosed symptomatic hypertension: . Undiagnosed asymptomatic hypertension: Any patient who has scheduled an elective surgery or change in medication during the 5 weeks of the study. Use of Neuromonics Device during duration of study or currently in Tinnitus Retraining Program during course of study. Any medical condition that, in the opinion of the investigators, confounds study results or places the subject at greater risk. Patients currently taking psychotropic medications including antidepressants, benzodiazepines, anticonvulsants, stimulants, antipsychotics, or anxiolytics. Tinnitus related to a Workman's Compensation claim or litigation-related event that is still pending.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Bimodal rTMS<br>Open-label and single-arm rTMS bimodal treatment with placement of magnet over Dorsolateral Prefrontal Cortex (DLPFC) and Temporoparietal Junction (TPJ) for 2 weeks of treatment (10 days) Stimulation Settings: DLPFC Stimulation Frequency 10 Hz Intensity 110% of motor threshold On 5 seconds Off 15 seconds Total Trains 80 per session Total pulses session 4000/session Duration session 26.6 minutes Total pulses (study) 40000 TPJ Stimulation Frequency 1 Hz Intensity 110% of motor threshold On 900 seconds Off 60 seconds Total Trains 2 per session Total Pulses session 1800 Duration session 31 minutes Total Pulses study 18000 | Device: Bimodal rTMS<br>* High frequency (10 Hz) at 110% of the motor threshold TMS delivered over the left dorsolateral prefrontal cortex, subsequently, a low frequency TMS (1 Hz) at 110% motor threshold will be delivered over 31 minutes over the TPJ area, according to the protocol below. DLPFC Stimulation Frequency 10 Hz Intensity 110% of motor threshold On 5 seconds Off 15 seconds Total Trains 80 per session Total pulses session 4000/session Duration session 26.6 minutes Total pulses (study) 40000 TPJ Stimulation Frequency 1 Hz Intensity 110% of motor threshold On 900 seconds Off 60 seconds Total Trains 2 per session Total Pulses session 1800 Duration session 31 minutes Total Pulses study 18000<br>* Other names: The rTMS system is a Magpro R 30 stimulator.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Subject will be queried for Adverse Events daily for 2 weeks of treatment. This is foremost a feasibility study, so measure of Adverse Events and relation to treatment is primary outcome. | Daily for 2 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tinnitus Handicap Inventory | Participant will complete the Tinnitus Handicap Inventory (THI)at the end of 2 weeks of treatment. Difference of the THI post treatmement minus baseline THI was calculated. Scale ranges in scores from 0 to 100 with 0 = no bother and 100 being the most bothered. | Baseline, 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tinnitus, bimodal stimulation, rTMS, Repetitive Transcranial Magnetic Stimulation