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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bimodal rTMS | Other | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bimodal rTMS | Device | 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 |
| 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. |
| 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 |
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Inclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Jay F Piccirillo, MD | Washington University School of Medicine, St. Louis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22217183 | Background | Burton H, Wineland A, Bhattacharya M, Nicklaus J, Garcia KS, Piccirillo JF. Altered networks in bothersome tinnitus: a functional connectivity study. BMC Neurosci. 2012 Jan 4;13:3. doi: 10.1186/1471-2202-13-3. | |
| 21422304 | Background | Piccirillo JF, Garcia KS, Nicklaus J, Pierce K, Burton H, Vlassenko AG, Mintun M, Duddy D, Kallogjeri D, Spitznagel EL Jr. Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus. Arch Otolaryngol Head Neck Surg. 2011 Mar;137(3):221-8. doi: 10.1001/archoto.2011.3. |
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Subjects were enrolled for one pre-treatments screening visits, received two weeks of rTMS treatment, and were assessed at the last treatment day. There was no additional follow-up.
All subjects were recruited from Washington University Otolaryngology and Audiology clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Bimodal rTMS | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Bimodal rTMS | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Pilot study based on convenience sample. | Posted | Number | participants | Daily for 2 weeks. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bimodal rTMS | 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 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jay F. Piccirillo | Washington University in Saint Louis | 314-362-8641 | piccirilloj@ent.wustl.edu |
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| ID | Term |
|---|---|
| D014012 | Tinnitus |
| ID | Term |
|---|---|
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
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| 22168528 | Background | Pierce KJ, Kallogjeri D, Piccirillo JF, Garcia KS, Nicklaus JE, Burton H. Effects of severe bothersome tinnitus on cognitive function measured with standardized tests. J Clin Exp Neuropsychol. 2012;34(2):126-34. doi: 10.1080/13803395.2011.623120. Epub 2011 Dec 14. |
| 21840364 | Background | Oh SY, Kim YK. Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Dec 1;35(8):1938-43. doi: 10.1016/j.pnpbp.2011.07.015. Epub 2011 Aug 5. |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
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| Secondary | 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. | Pilot study convenience sample | Posted | Median | Full Range | units on a scale | Baseline, 2 weeks |
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| 0 |
| 5 |
| 0 |
| 5 |
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| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |