Tinnitus
Conditions
Keywords
Tinnitus, Transcranial Magnetic Stimulation, TMS, rTMS
Brief summary
One out of every five people experiences tinnitus (a ringing, buzzing, or roaring sound in the ear) ranging from mild to severe impairment. To date, there are no effective therapies available that have been shown to decrease tinnitus awareness. The purpose of this study is to evaluate a treatment option for tinnitus that uses a technique called Repetitive Transcranial Magnetic Stimulation (rTMS), which could prove to be an effective means of alleviating or reducing the symptoms of tinnitus.
Detailed description
Up to 60 subjects, including males and females ages 19-89 years old and of all races, and with tinnitus severe enough to seek medical attention, will be enrolled in this study. All participants must be evaluated or have documentation of being evaluated prior to beginning therapy with rTMS in order to confirm eligibility and to rule out any medically treatable causes of tinnitus. An MRI scan of the head may or may not be required, depending upon the results of this evaluation, in order to rule out specific middle ear pathologies. This study will require participation in at least three weeks (4 weekdays per week) of rTMS sessions, including two active weeks and a sham (or placebo) week. There will be a three week washout period following each treatment week. At the completion of the three treatment weeks, subjects who have noticed an improvement in their tinnitus will have the option of participating in a maintenance rTMS program providing up to 8 additional weeks of treatment.
Interventions
DEVICESham rTMS - Sham repetitive transcranial magnetic stimulation
Sham rTMS will be delivered using a commercially available sham coil and targeted to the same brain site in the temporal lobe and in a manner identical to that for active rTMS except that scalp electrodes are used to stimulate the temporalis muscle electrically during sham stimulation to replicate the feel of active TMS.
DEVICEActive 1 Hz rTMS - Active repetitive transcranial magnetic stimulation delivered at 1 Hz frequency
Active rTMS will be targeted either to the mid-superior temporal gyrus opposite the ear with loudest tinnitus or to the same region in the left hemisphere if no asymmetry in tinnitus is present. 1 Hz active rTMS will be delivered at 110% of motor threshold (MT) for a total of 1800 magnetic pulses per session, 4 sessions per week.
DEVICEActive 10 Hz rTMS - active repetitive transcranial magnetic stimulation delivered at 10 Hz frequency
Active rTMS will be targeted either to the mid-superior temporal gyrus opposite the ear with loudest tinnitus or to the same region in the left hemisphere if no asymmetry in tinnitus is present. 10 Hz active rTMS will be delivered at 110% of motor threshold (MT) for a total of 1800 magnetic pulses per session, 4 sessions per week.
Sponsors
National Institutes of Health (NIH)
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
per protocol and informed consent: * Diagnosis of tinnitus established through a history and physical exam or review of records. * Subjects 19-89 years of age * Tinnitus present for at least 6 months and severe enough to seek medical attention * Subjects taking SSRI's (a class of anti-depressant medications)and benzodiazepines (a class of anti-anxiety medications) for depression or anxiety related to tinnitus must be stable on their current dose for at least 3 months and must not alter their dose or medication during their involvement with this study * Subjects must agree to avoid consuming alcohol within 72 hours of each rTMS session * Female subjects of childbearing potential must demonstrate a negative pregnancy test during their initial clinic visit and must agree to use effective contraception during their participation in this study * Subjects must sign an informed consent and agree to comply with study and follow-up procedures, including completion of all necessary questionnaires and testing, as well as, being video-recorded for safety purposes during rTMS sessions * Subjects must speak and comprehend English adequately to understand and complete any study-related instructions and questionnaires
Exclusion criteria
per protocol and informed consent: For rTMS * Subjects or any of their 1st-degree relatives must not have been diagnosed with epilepsy * Subjects must not have a history of seizure disorder or migraines * Subjects must not have any history of a brain aneurysm, stroke, previous cranial neurosurgery, acoustic neuroma, glomus tumor, active Menniere's Disease, profound hearing loss (greater than 90 dB at 4000 Hz), or any major neurological or psychiatric disorders (excluding depression or anxiety related to tinnitus) * Medications that lower seizure threshold or reduce cortical excitation (i.e., tricyclic antidepressants, bupropion or anticonvulsants) * Subjects must not have any history of a head injury that resulted in a loss of consciousness for more than 10 minutes * Subjects must not be pregnant or refuse to utilize effective contraception during their participation in this study For MRI * Subjects must not have any metal implants or devices in the head or neck or a pacemaker. * Subjects must not have severe claustrophobia if they are to have an MRI. * Significant abnormalities must not be present on acquired or existing CT or MRI image of the head.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Analogue Rating of Tinnitus Awareness. | from baseline to: day 6 (sham), day 25 (sham w/o), day 29 (1st active TX), day 50 (1st active w/o), day 50 (2nd active TX), day 76 (2nd active w/o). | Change from baseline on the daily analogue rating of tinnitus awareness. Analogue ratings are a validated self report instrument assessing subjects awareness of tinnitus in daily life. Possible scores range from 0 (no tinnitus) to 100 (painfully loud tinnitus). Change equals the average rating for a given treatment week or washout period minus the average rating over three baseline assessments. |
Countries
United States
Participant flow
Recruitment details
A total of 58 participants were enrolled. Recruitment used a waitlist of subjects who already expressed interest in tinnitus studies and from advertisement.
Pre-assignment details
Of the 58 subjects enrolled, only 39 were assigned to study groups. Two subjects who initially failed screening were re-enrolled via a waiver before assignment. Ten had participated in an early version of the protocol that was not comparable. Seven subjects dropped out after baseline. So 2+10+7= the 19 participants who were enrolled but not started in the participant flow.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Enrolled in the Study Baseline information is reported for all subjects enrolled. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | All Subjects Enrolled in the Study |
|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 12.2 |
| Baseline analogue ratings of tinnitus awareness | 58.72 units on a scale STANDARD_DEVIATION 22.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 56 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 27 | 0 / 31 |
| other Total, other adverse events | 12 / 27 | 8 / 31 |
| serious Total, serious adverse events | 1 / 27 | 0 / 31 |
Outcome results
Primary
Change From Baseline on the Analogue Rating of Tinnitus Awareness.
Change from baseline on the daily analogue rating of tinnitus awareness. Analogue ratings are a validated self report instrument assessing subjects awareness of tinnitus in daily life. Possible scores range from 0 (no tinnitus) to 100 (painfully loud tinnitus). Change equals the average rating for a given treatment week or washout period minus the average rating over three baseline assessments.
Time frame: from baseline to: day 6 (sham), day 25 (sham w/o), day 29 (1st active TX), day 50 (1st active w/o), day 50 (2nd active TX), day 76 (2nd active w/o).
Population: The analysis population includes 36 subjects who completed the all baseline, sham rTMS, sham washout, active 1 Hz rTMS, 1Hz washout, active 10Hz rTMS and 10Hz washout periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham rTMS | Change From Baseline on the Analogue Rating of Tinnitus Awareness. | -4.08 units on a scale | Standard Error 3.72 |
| Sham Washout | Change From Baseline on the Analogue Rating of Tinnitus Awareness. | -4.70 units on a scale | Standard Error 3.9 |
| 1 Hz Active rTMS | Change From Baseline on the Analogue Rating of Tinnitus Awareness. | -9.82 units on a scale | Standard Error 3.72 |
| 1 Hz Washout | Change From Baseline on the Analogue Rating of Tinnitus Awareness. | -9.89 units on a scale | Standard Error 3.91 |
| 10 Hz Active rTMS | Change From Baseline on the Analogue Rating of Tinnitus Awareness. | -10.85 units on a scale | Standard Error 3.85 |
| 10 Hz Washout | Change From Baseline on the Analogue Rating of Tinnitus Awareness. | -9.43 units on a scale | Standard Error 4.06 |
p-value: 0.04Mixed Models Analysis
p-value: 0.02Mixed Models Analysis
p-value: 0.2Mixed Models Analysis
p-value: 0.19Mixed Models Analysis