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| ID | Type | Description | Link |
|---|---|---|---|
| R01DC009095 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Deafness and Other Communication Disorders (NIDCD) | NIH |
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The goal of this trial to see if repetitive transcranial magnetic stimulation (rTMS) to the hearing area of the brain can lessen the perception of tinnitus. rTMS uses a strong magnet and when placed against the scalp generates a small electrical field within the brain. Depending on the frequency of the stimulation, this electrical field can either decrease or increase the electrical excitability of the brain. In this study, low-frequency stimulation will be used, which is thought to decrease nerve activity. It is this electrical excitability of the brain that is thought to be responsible for tinnitus.
The hypothesis of this study is that rTMS can decrease the perception of tinnitus.
This will be a cross-over randomized trial. The order of the treatments received will be randomly selected and the participant will not be told which treatment they are receiving. Subjects will fall into one of the four treatment groups described below:
For the washout period between the two interventions, we will plan a minimum of 2 weeks to avoid the problem of carryover effects. Prior to starting the next intervention after the washout period, we will re-assess subject's tinnitus severity. To ensure no carryover effect, the washout period will be extended for those subjects whose tinnitus severity, as defined by the THI, is more than 20 points different than their baseline THI score.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1. rTMS | Experimental | Stimulation Settings: Frequency -- 1Hz on 330 sec (5 min 30 sec.) per train for the first 5 trains with the last train 350 sec. (5 min. 50 sec.) in duration Off -- 90 sec (1 min. 30 sec.) Intensity -- 110% of motor threshold Duration -- 42½ minutes (total 2000 pulses in 6 trains) |
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| 2. Sham rTMS | Sham Comparator | Sham rTMS appears identical to and mimics sounds and sensations of active magnet. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rTMS | Device | Stimulation Settings: Frequency -- 1Hz on 330 sec (5 min 30 sec.) per train for the first 5 trains with the last train 350 sec. (5 min. 50 sec.) in duration Off -- 90 sec (1 min. 30 sec.) Intensity -- 110% of motor threshold Duration -- 42½ minutes (total 2000 pulses in 6 trains) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in THI (Tinnitus Handicap Inventory) | Tinnitus Handicap Inventory (THI) is a measure of bother from tinnitus. THI is measured as a score in a scale ranging from 0=No bother to 100=Extremely Bothered. THI score post active rTMS treatment minus THI score pre active rTMS treatment will provide the change in THI score due to active treatment. THI score post rTMS sham minus THI score pre rTMS sham will provide change in THI due to sham. The difference of THI change due to active treatment minus THI change due to sham will provide the THI change that is our primary outcome measure. | baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater | PGIC is a 7 point scale ranging from -3 to +3,with 0 meaning no change,negative values reporting worsening of symptoms(Tinnitus), and values of +1 or above reporting perceived improvement of Tinnitus. PGIC score post active rTMS treatment treatment will provide subject's impression of change in tinnitue due to active treatment.PGIC score post rTMS sham will provide subject's impression of change in tinnitus due to sham. Number of subjects with scores of 1 or above are recorded to perceive improvement due to treatment of the corresponding study arm. |
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On-line eligibility screening:
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jay F Piccirillo, MD, CPI | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University Medical Center | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21422304 | Result | 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. | |
| 22168528 | Result | 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. |
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Screen failure reasons included: Screening for clinical depression or other significant psychiatric conditions, history of significant head injury, inability to obtain motor threshold with repetitive transcranial magnetic stimulation (rTMS), MRI claustrophobia, and two patients elected not to participate.
Enrollment period: August, 2008 to June, 2010
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| ID | Title | Description |
|---|---|---|
| FG000 | Active Then Sham rTMS Treatment (2 Weeks) | Active rTMS Treatment for 2 weeks followed by 2 weeks wash-out and then 2 weeks sham. Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit. |
| FG001 | Sham Then Active rTMS Treatment (2 Weeks) | Sham treatment for 2 weeks followed by 2 weeks wash-out and then 2 weeks Active rTMS Treatment.Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit. |
| FG002 | Active Then Sham rTMS Treatment (4 Weeks) | Active rTMS Treatment for 4 weeks followed by 2 weeks wash-out and then 4 weeks sham.Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.One subject had a drop of THI larger than 20 points from baseline after first arm of treatment and did not get the second arm. |
| FG003 | Sham Then Active rTMS Treatment (4 Weeks) | Sham treatment for 4 weeks followed by 2 weeks wash-out and then 4 weeks Active rTMS Treatment. Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Treatment (2 or 4 Weeks) |
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| Washout (2 Weeks) |
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| Second Treatment (2 or 4 Weeks) |
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| ID | Title | Description |
|---|---|---|
| BG000 | 2 Week Treatment | Treatment (either active rTMS or sham)for 2 weeks followed by 2 week wash-out then treatment (opposite of first assignment)for 2 weeks |
| BG001 | 4 Week Treatment |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Change in THI (Tinnitus Handicap Inventory) | Tinnitus Handicap Inventory (THI) is a measure of bother from tinnitus. THI is measured as a score in a scale ranging from 0=No bother to 100=Extremely Bothered. THI score post active rTMS treatment minus THI score pre active rTMS treatment will provide the change in THI score due to active treatment. THI score post rTMS sham minus THI score pre rTMS sham will provide change in THI due to sham. The difference of THI change due to active treatment minus THI change due to sham will provide the THI change that is our primary outcome measure. | Study participant that successfully completed both study parts active rTMS treatment and sham rTMS treatment were included in analysis. | Posted | Median | 95% Confidence Interval | units on a scale | baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks) |
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Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI > 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
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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 | 2 Weeks Treatment | Treatment (either active rTMS or sham) for two weeks followed by 2 weeks wash-out then treatment (opposite of first assignment)for two weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Worsening of Tinnitus | Ear and labyrinth disorders | Non-systematic Assessment | Some reported worsening of tinnitus that was later followed by improvement of tinnitus. In all cases the worsening was temporary, no longer than a day or two. |
Excluding subjects with Beck Depression Index of above 14 we treated an exclusive group of the Very bothered tinnitus patients, which may not be representative of the tinnitus population as a whole.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jay F. Piccirillo | Washington University | 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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| End of each treatment period (2 or 4 weeks) |
| 22217183 | Result | 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. |
| 23599075 | Derived | Piccirillo JF, Kallogjeri D, Nicklaus J, Wineland A, Spitznagel EL Jr, Vlassenko AG, Benzinger T, Mathews J, Garcia KS. Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus: four-week stimulation trial. JAMA Otolaryngol Head Neck Surg. 2013 Apr;139(4):388-95. doi: 10.1001/jamaoto.2013.233. |
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| COMPLETED |
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| NOT COMPLETED |
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Treatment (either active rTMS or sham)for 4 weeks followed by 2 week wash-out then treatment (opposite of first assignment)for 4 weeks
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Full Range | 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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Daily rTMS for about 1 hour with active device settings (stimulation intensity at 110% of motor threshold), for 2 weeks.
| OG001 | 2-Weeks Sham rTMS Treatment | Daily sham-rTMS for about 1 hour with sham device settings for 2 weeks. |
| OG002 | 4-weeks rTMS Active Treatment | Daily rTMS for about 1 hour with active device settings (stimulation intensity at 110% of motor threshold), for 4 weeks. |
| OG003 | 4-weeks rTMS Sham Treatment | Daily sham-rTMS for about 1 hour with sham device settings for 4 weeks. |
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| Secondary | Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater | PGIC is a 7 point scale ranging from -3 to +3,with 0 meaning no change,negative values reporting worsening of symptoms(Tinnitus), and values of +1 or above reporting perceived improvement of Tinnitus. PGIC score post active rTMS treatment treatment will provide subject's impression of change in tinnitue due to active treatment.PGIC score post rTMS sham will provide subject's impression of change in tinnitus due to sham. Number of subjects with scores of 1 or above are recorded to perceive improvement due to treatment of the corresponding study arm. | Study participant that successfully completed both study parts active rTMS treatment and sham rTMS treatment were included in analysis. | Posted | Number | participants | End of each treatment period (2 or 4 weeks) |
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| 0 |
| 14 |
| 7 |
| 14 |
| EG001 | Four Week Treatment | Treatment (either active rTMS or sham)for 4 weeks followed by 2 week wash-out then treatment (opposite of first assignment)for 4 weeks | 0 | 20 | 3 | 20 |
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| Ear Pain | Ear and labyrinth disorders | Non-systematic Assessment | One subject complained of ear pain, subject thought it was related to magnet placement. |
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| Worsening of Menopausal Symptoms | Reproductive system and breast disorders | Non-systematic Assessment | 1 Subject complained of increased hot flashes and irritability for 10 days during treatment. Unsure if related to treatment. |
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| Neck Stiffness or Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Lightheaded feeling | Nervous system disorders | Non-systematic Assessment | One subject reported feeling lightheaded for a few minutes after treatment for 2 days of treatment. Resolved on its own each time, and did not continue. |
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| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |