Subjective Tinnitus
Conditions
Keywords
tinnitus, subjective tinnitus, therapy, repetitive transcranial magnetic stimulation, clinical trial
Brief summary
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.
Detailed description
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: 1. 2 weeks of active rTMS treatment followed by washout and then by 2 weeks sham 2. 2 weeks of sham followed by washout and then 2 weeks of active rTMS treatment 3. 4 weeks of active rTMS treatment followed by washout and then 4 weeks of sham 4. 4 weeks of sham followed by washout and then 4 weeks of active rTMS treatment 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.
Interventions
DEVICErTMS
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)
Sponsors
National Institute on Deafness and Other Communication Disorders (NIDCD)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
On-line eligibility screening: https://tinnitus.wustl.edu/ Inclusion Criteria: * Men and women between the ages of 18 and 60 years. * Subjective, unilateral or bilateral, non-pulsatile tinnitus of 6 month's duration or greater. * Tinnitus Handicap Inventory (THI) score of 38 or greater. * Subjects of child-bearing potential using an appropriate form of birth control acceptable to the research team and with a negative urine pregnancy test or undergone sterilization procedure. * Able to give informed consent. * Available for once daily therapy, during working hours, Mon.-Fri. * English-speaking.
Exclusion criteria
* Patients experiencing tinnitus related to cochlear implantation, retrocochlear lesion, or other known anatomic/structural lesions of the ear and temporal bone. * Patients with hyperacusis or misophonia (hyper-sensitivity to loud noises). * History of seizures, history of loss of consciousness requiring medical care, any other CNS pathology that increases a subject's risk for treatment with rTMS. * Patients with cardiac pacemakers, intracardiac lines, implanted medication pumps, implanted electrodes in the brain, other intracranial metal objects with the exception of dental fillings, or any other contraindication for MRI scan. * Any contraindication for receiving FDG PET, as determined by established clinical criteria. * Patients with an acute or chronic unstable medical condition which, in the opinion of the investigator, would require stabilization prior to initiation of magnetic stimulation. * Patients with any active ear disease that, in the opinion of the PI, needs to be further evaluated. * Patients with symptoms of depression as evidenced by a score of 14 or greater on the Beck Depression Inventory or, in the opinion of the psychiatric sub-investigator demonstrates active mood symptoms that meet DSM-IV-TR criteria for Major Depressive Disorder. * Any psychiatric co-morbidity that, in the opinion of the psychiatric sub-investigator, may complicate the interpretation of study results. * Pregnancy * Currently breast-feeding * Previous treatment with rTMS * Patients with tinnitus related to Workman's Compensation claim or litigation-related event. * Patients with a history of diabetes. * Fasting glucose \> 150mg/Dl. * Patients taking any medication(s), in the opinion of the investigator, that is(are) deemed to be etiologically related to the development of tinnitus. * Unable to elicit a motor threshold with rTMS. * A Mini-Mental Status Exam score less than 27. * Untreated or newly diagnosed hypertension, (systolic blood pressures above 140 mm or diastolic pressure above 90 mm). * Patients with a history of claustrophobia. * Inability to lay flat for 2 hours. * Active alcohol and/or drug dependence or history of alcohol and/or ETOH dependence within the last year. * Any medical condition that, in the opinion of the investigators, confounds study results or places the subject at greater risk. * Unable to provide informed consent. * Any exclusions from radiology screening for MRI or PET scanning.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in THI (Tinnitus Handicap Inventory) | baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater | End of each treatment period (2 or 4 weeks) | 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. |
Countries
United States
Participant flow
Recruitment details
Enrollment period: August, 2008 to June, 2010
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 14 |
| 4 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 | 20 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Treatment (2 or 4 Weeks) | Withdrawal by Subject | 0 | 0 | 1 | 4 |
| Second Treatment (2 or 4 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 4 Week Treatment | 2 Week Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 14 Participants | 34 Participants |
| Age, Continuous | 42 years | 52 years FULL_RANGE 5.1 | 50 years |
| Region of Enrollment United States | 20 participants | 14 participants | 34 participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 14 | 3 / 20 |
| serious Total, serious adverse events | 0 / 14 | 0 / 20 |
Outcome results
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.
Time frame: baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks)
Population: Study participant that successfully completed both study parts active rTMS treatment and sham rTMS treatment were included in analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2-weeks rTMS Active Treatment | Change in THI (Tinnitus Handicap Inventory) | -5 units on a scale |
| 2-Weeks Sham rTMS Treatment | Change in THI (Tinnitus Handicap Inventory) | -6 units on a scale |
| 4-weeks rTMS Active Treatment | Change in THI (Tinnitus Handicap Inventory) | -10 units on a scale |
| 4-weeks rTMS Sham Treatment | Change in THI (Tinnitus Handicap Inventory) | -6 units on a scale |
Comparison: The null hypothesis for this study was the difference between the change in THI score due to active rTMS treatment and the change in THI score due to rTMS sham was not different from 0.p-value: 0.94495% CI: [-6, 4]Wilcoxon signed rank test
Comparison: The null hypothesis for this study was the difference between the change in THI score due to 4 weeks active rTMS treatment and the change in THI score due to 4 weeks rTMS sham was not different from 0.p-value: 0.67495% CI: [-9, 10]Wilcoxon signed rank test
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.
Time frame: End of each treatment period (2 or 4 weeks)
Population: Study participant that successfully completed both study parts active rTMS treatment and sham rTMS treatment were included in analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2-weeks rTMS Active Treatment | Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater | 1 participants |
| 2-Weeks Sham rTMS Treatment | Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater | 3 participants |
| 4-weeks rTMS Active Treatment | Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater | 3 participants |
| 4-weeks rTMS Sham Treatment | Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater | 5 participants |