Tinnitus
Conditions
Keywords
Tinnitus, Ringing in the ear
Brief summary
The goal of the study is to reduce tinnitus (ringing in the ear) loudness and improve the quality of life for those that are affected by tinnitus. This study will enroll subjects who have constant and bothersome tinnitus with no greater than a mild hearing loss up to 6 kHz, and no greater than a moderate hearing loss in the tinnitus frequencies. Subjects must also have the ability to alter the loudness or pitch of the ringing in their ears by performing a head, neck, face, or upper body movement. Subjects will be given both the treatment and sham arms (the study will randomly assign which arm is administered first) and will have a washout period of 6 weeks after each arm. The study will take approximately 36 weeks for subjects to complete and will enroll up to 300 individuals.
Interventions
DEVICEBurst-SCS/sham SCS
The auditory stimulus will be individualized based on subject baseline audiogram and tinnitus test results and is presented through a calibrated earphone. Somatosensory stimulation will be delivered by pads positioned on the cheek overlying the trigeminal ganglion or on the neck at overlying cervical nerves, c1 or c2, determined by the manner in which the subject can modulate the tinnitus. For each arm of the study subjects will have daily treatments for 30-60 minutes for 6 weeks.
DEVICESham SCS/Burst-SCS
Somatosensory stimulation will be delivered by pads positioned on the cheek overlying the trigeminal ganglion or on the neck at overlying cervical nerves, c1 or c2, determined by the manner in which the subject can modulate the tinnitus. The auditory stimulus will be individualized based on subject baseline audiogram and tinnitus test results and is presented through a calibrated earphone. For each arm of the study subjects will have daily treatments for 30-60 minutes for 6 weeks.
Sponsors
National Institute of Mental Health (NIMH)
University of Michigan
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Must report constant, subjective, preferably unilateral tinnitus without any active external or middle ear pathology. * No greater than a mild hearing loss up to 6 kHz, and no greater than a moderate hearing loss at the tinnitus frequencies. * Must be able to modulate their tinnitus with a somatic maneuver * Preferably onset of tinnitus less than one year ago, but present for at least 6 months. Tinnitus should be bothersome. * Absence of retrocochlear pathology/8th nerve lesion * No participation in a tinnitus treatment regimen within the past six months or participation in the University of Michigan stage 1 clinical trial.
Exclusion criteria
* Diagnosis of Meniere's disease * Diagnosis of Semicircular Canal Dehiscence * Unilateral or bilateral cochlear implant recipients * Diagnosis of acoustic neuroma * Evidence of retrocochlear disease * Certain medications and conditions (will be reviewed at screening)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Objective Tinnitus Loudness | Up to 24 weeks | Change in Tinnitus by the TinnTester software. Participants are guided through a self-directed computerized assessment software that estimates how loud (in decibels) they perceive their tinnitus to be (TinnTester). These will be collected weekly during each treatment arm and washout. Absolute differences are averaged relative to baseline to determine loudness change. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. |
| Change in Tinnitus Functional Index (TFI) | Up to 36 weeks | TFI is a clinical questionnaire that assesses tinnitus impact on a participant's quality of life. It uses a scale of 0 - 100 where 0 means no negative impact on quality of life from tinnitus and 100 is devastating impact. These will be collected weekly during each treatment arm and washout. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and PSM 36 weeks, and the same pattern for the Sham First group. Values presented are all shown as change from baseline. |
| Tinnitus Handicap Inventory (THI) | Up to 24 weeks | A 25 item questionnaire which assesses subjective impacts of tinnitus related to quality of life on a 100 point numeric scale. Scores 17 points or higher are considered bothersome tinnitus. The higher scores reflecting greater self-perceived tinnitus handicap. These will be collected weekly during each treatment arm and washout. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. Values presented are all shown as change from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | Up to 24 weeks | Participants are guided through a self-directed computerized assessment software that estimates how similar their tinnitus is to a set of select sounds rated on a 0 - 100 scale where 0 is not similar & 100 is identical. Treatment will relate outcomes to tinnitus bandwidth by these measurements and determine whether the treatment alters bandwidth. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. Values presented are all shown as change from baseline. |
| Changes in Minimum Masking Level (MML) | Up to 24 weeks | Determine if the MML for a high-pass 2kHz broadband noise is change in the active treatment arm. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. Values presented are all shown as change from baseline. |
| Tinnitus Hearing Survey | Up to 24 weeks | This is a 10-question survey with a scale from 0 to 4 to determine if active treatment has an effect or interaction with perceived handicap due to hearing loss and sound level tolerance. Categories are comprised of tinnitus, hearing, and sound tolerance. An answer of 0 is no/not a problem, and an answer of 4 is yes/a very big problem. The range for the total score is 0 - 40 with lower numbers meaning fewer hearing problems and higher numbers meaning more tinnitus, or hearing or sound tolerance problems. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Then Sham Active: Bimodal auditory-somatosensory stimulation
Sham: Sham Bimodal auditory-somatosensory stimulation
Subjects receive both an active treatment and a sham treatment. The subjects will be blinded to which treatment they are receiving. Both treatments are delivered using a take-home device programmed in the lab.
During active treatment, the device will deliver electric somatosensory and auditory stimulation.
Sham SCS/Burst-SCS: Somatosensory stimulation will be delivered by pads positioned on the cheek overlying the trigeminal ganglion or on the neck at overlying cervical nerves, c1 or c2, determined by the manner in which the subject can modulate the tinnitus.
The auditory stimulus will be individualized based on subject baseline audiogram and tinnitus test results and is presented through a calibrated earphone.
For each arm of the study subjects will have daily treatments for 30-60 minutes for 6 weeks. | 49 |
| Sham Then Active Active: Bimodal auditory-somatosensory stimulation
Sham: Sham Bimodal auditory-somatosensory stimulation
Subjects receive both a sham treatment and an active treatment. The subjects will be blinded to which treatment they are receiving. Both treatments are delivered using a take-home device programmed in the lab.
During active treatment, the device will deliver electric somatosensory and auditory stimulation.
Burst-SCS/sham SCS: The auditory stimulus will be individualized based on subject baseline audiogram and tinnitus test results and is presented through a calibrated earphone.
Somatosensory stimulation will be delivered by pads positioned on the cheek overlying the trigeminal ganglion or on the neck at overlying cervical nerves, c1 or c2, determined by the manner in which the subject can modulate the tinnitus.
For each arm of the study subjects will have daily treatments for 30-60 minutes for 6 weeks. | 50 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 13 | 13 |
Baseline characteristics
| Characteristic | Sham Then Active | Total | Active Then Sham |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 1.8 | 47.1 years STANDARD_DEVIATION 1.8 | 47.0 years STANDARD_DEVIATION 1.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 96 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Minimum Masking Level (MML) | 33.0 dB (sensation level) STANDARD_DEVIATION 12.2 | 34.2 dB (sensation level) STANDARD_DEVIATION 12.6 | 35.4 dB (sensation level) STANDARD_DEVIATION 12.9 |
| Objective Tinnitus Loudness | 55.1 decibels STANDARD_DEVIATION 13.4 | 56.1 decibels STANDARD_DEVIATION 13.5 | 57.0 decibels STANDARD_DEVIATION 13.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 89 Participants | 44 Participants |
| Region of Enrollment United States | 50 Participants | 99 Participants | 49 Participants |
| Sex: Female, Male Female | 22 Participants | 39 Participants | 17 Participants |
| Sex: Female, Male Male | 28 Participants | 60 Participants | 32 Participants |
| Tinnitus Functional Index (TFI) | 42.6 score on a scale STANDARD_DEVIATION 16.8 | 42.9 score on a scale STANDARD_DEVIATION 15.1 | 43.1 score on a scale STANDARD_DEVIATION 13.4 |
| Tinnitus Handicap Inventory (THI) | 34.9 score on a scale STANDARD_DEVIATION 18.3 | 36.4 score on a scale STANDARD_DEVIATION 18 | 37.9 score on a scale STANDARD_DEVIATION 17.7 |
| Tinnitus Hearing Survey | 5.2 score on a scale STANDARD_DEVIATION 3 | 5.6 score on a scale STANDARD_DEVIATION 2.8 | 5.9 score on a scale STANDARD_DEVIATION 2.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 99 | 0 / 86 | 0 / 80 | 0 / 89 | 0 / 82 | 0 / 76 |
| other Total, other adverse events | 3 / 99 | 19 / 86 | 9 / 80 | 16 / 89 | 12 / 82 | 1 / 76 |
| serious Total, serious adverse events | 0 / 99 | 0 / 86 | 0 / 80 | 0 / 89 | 0 / 82 | 0 / 76 |
Outcome results
Primary
Change in Objective Tinnitus Loudness
Change in Tinnitus by the TinnTester software. Participants are guided through a self-directed computerized assessment software that estimates how loud (in decibels) they perceive their tinnitus to be (TinnTester). These will be collected weekly during each treatment arm and washout. Absolute differences are averaged relative to baseline to determine loudness change. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group.
Time frame: Up to 24 weeks
Population: Because of the crossover nature of this trial, and to determine whether spillover effects were present, participants are represented multiple times for each segment of the trial in which they participated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active First | Change in Objective Tinnitus Loudness | -6.1 decibels sensation level (dB SL) | Standard Error 1.8 |
| Active-First Washout | Change in Objective Tinnitus Loudness | -9.5 decibels sensation level (dB SL) | Standard Error 2.1 |
| Active-First Then Sham | Change in Objective Tinnitus Loudness | -10.2 decibels sensation level (dB SL) | Standard Error 2.3 |
| Active-First-Then-Sham Washout | Change in Objective Tinnitus Loudness | -11.0 decibels sensation level (dB SL) | Standard Error 2.5 |
| Sham First | Change in Objective Tinnitus Loudness | -3.7 decibels sensation level (dB SL) | Standard Error 1.3 |
| Sham-First Washout | Change in Objective Tinnitus Loudness | -4.7 decibels sensation level (dB SL) | Standard Error 1.5 |
| Sham-First Then Active | Change in Objective Tinnitus Loudness | -5.8 decibels sensation level (dB SL) | Standard Error 2.3 |
| Sham-First-Then-Active Washout | Change in Objective Tinnitus Loudness | -4.9 decibels sensation level (dB SL) | Standard Error 2.4 |
Primary
Change in Tinnitus Functional Index (TFI)
TFI is a clinical questionnaire that assesses tinnitus impact on a participant's quality of life. It uses a scale of 0 - 100 where 0 means no negative impact on quality of life from tinnitus and 100 is devastating impact. These will be collected weekly during each treatment arm and washout. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and PSM 36 weeks, and the same pattern for the Sham First group. Values presented are all shown as change from baseline.
Time frame: Up to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active First | Change in Tinnitus Functional Index (TFI) | -12.0 Points on a Scale | Standard Error 2.3 |
| Active-First Washout | Change in Tinnitus Functional Index (TFI) | -13.1 Points on a Scale | Standard Error 2.4 |
| Active-First Then Sham | Change in Tinnitus Functional Index (TFI) | -16.8 Points on a Scale | Standard Error 2.4 |
| Active-First-Then-Sham Washout | Change in Tinnitus Functional Index (TFI) | -15.9 Points on a Scale | Standard Error 2 |
| Sham First | Change in Tinnitus Functional Index (TFI) | -12.1 Points on a Scale | Standard Error 2.7 |
| Sham-First Washout | Change in Tinnitus Functional Index (TFI) | -6.5 Points on a Scale | Standard Error 1.9 |
| Sham-First Then Active | Change in Tinnitus Functional Index (TFI) | -8.3 Points on a Scale | Standard Error 2 |
| Sham-First-Then-Active Washout | Change in Tinnitus Functional Index (TFI) | -13.8 Points on a Scale | Standard Error 2.7 |
| Sham-First-Then-Active Washout | Change in Tinnitus Functional Index (TFI) | -13.4 Points on a Scale | Standard Error 2.8 |
| Sham-First Post-Study Monitoring (PSM) Period | Change in Tinnitus Functional Index (TFI) | -15.3 Points on a Scale | Standard Error 2.6 |
Primary
Tinnitus Handicap Inventory (THI)
A 25 item questionnaire which assesses subjective impacts of tinnitus related to quality of life on a 100 point numeric scale. Scores 17 points or higher are considered bothersome tinnitus. The higher scores reflecting greater self-perceived tinnitus handicap. These will be collected weekly during each treatment arm and washout. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. Values presented are all shown as change from baseline.
Time frame: Up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active First | Tinnitus Handicap Inventory (THI) | -5.8 Points on a Scale | Standard Error 2.1 |
| Active-First Washout | Tinnitus Handicap Inventory (THI) | -6.4 Points on a Scale | Standard Error 1.9 |
| Active-First Then Sham | Tinnitus Handicap Inventory (THI) | -8.0 Points on a Scale | Standard Error 2.6 |
| Active-First-Then-Sham Washout | Tinnitus Handicap Inventory (THI) | -6.9 Points on a Scale | Standard Error 2 |
| Sham First | Tinnitus Handicap Inventory (THI) | -1.6 Points on a Scale | Standard Error 1.5 |
| Sham-First Washout | Tinnitus Handicap Inventory (THI) | -2.2 Points on a Scale | Standard Error 1.7 |
| Sham-First Then Active | Tinnitus Handicap Inventory (THI) | -5.3 Points on a Scale | Standard Error 2.8 |
| Sham-First-Then-Active Washout | Tinnitus Handicap Inventory (THI) | -4.6 Points on a Scale | Standard Error 2.7 |
Secondary
Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software)
Participants are guided through a self-directed computerized assessment software that estimates how similar their tinnitus is to a set of select sounds rated on a 0 - 100 scale where 0 is not similar & 100 is identical. Treatment will relate outcomes to tinnitus bandwidth by these measurements and determine whether the treatment alters bandwidth. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. Values presented are all shown as change from baseline.
Time frame: Up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active First | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 7.1 units on a scale | Standard Error 0.9 |
| Active-First Washout | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 8.4 units on a scale | Standard Error 1 |
| Active-First Then Sham | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 9.5 units on a scale | Standard Error 1 |
| Active-First-Then-Sham Washout | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 10.3 units on a scale | Standard Error 1.2 |
| Sham First | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 8.0 units on a scale | Standard Error 0.9 |
| Sham-First Washout | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 8.5 units on a scale | Standard Error 1 |
| Sham-First Then Active | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 10.3 units on a scale | Standard Error 1.4 |
| Sham-First-Then-Active Washout | Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software) | 11.0 units on a scale | Standard Error 1.5 |
Secondary
Changes in Minimum Masking Level (MML)
Determine if the MML for a high-pass 2kHz broadband noise is change in the active treatment arm. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group. Values presented are all shown as change from baseline.
Time frame: Up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active First | Changes in Minimum Masking Level (MML) | -5.1 dB (sensation level) | Standard Deviation 2.3 |
| Active-First Washout | Changes in Minimum Masking Level (MML) | -1.1 dB (sensation level) | Standard Deviation 2.3 |
| Active-First Then Sham | Changes in Minimum Masking Level (MML) | -2.0 dB (sensation level) | Standard Deviation 2.9 |
| Active-First-Then-Sham Washout | Changes in Minimum Masking Level (MML) | 0.2 dB (sensation level) | Standard Deviation 2 |
| Sham First | Changes in Minimum Masking Level (MML) | -2.7 dB (sensation level) | Standard Deviation 1.6 |
| Sham-First Washout | Changes in Minimum Masking Level (MML) | -1.6 dB (sensation level) | Standard Deviation 1.5 |
| Sham-First Then Active | Changes in Minimum Masking Level (MML) | 0.0 dB (sensation level) | Standard Deviation 2.1 |
| Sham-First-Then-Active Washout | Changes in Minimum Masking Level (MML) | -0.1 dB (sensation level) | Standard Deviation 3.3 |
Secondary
Tinnitus Hearing Survey
This is a 10-question survey with a scale from 0 to 4 to determine if active treatment has an effect or interaction with perceived handicap due to hearing loss and sound level tolerance. Categories are comprised of tinnitus, hearing, and sound tolerance. An answer of 0 is no/not a problem, and an answer of 4 is yes/a very big problem. The range for the total score is 0 - 40 with lower numbers meaning fewer hearing problems and higher numbers meaning more tinnitus, or hearing or sound tolerance problems. For each of the two arms, Active Then Sham and Sham Then Active, data is presented at the end of each arm phase group, in six week intervals. Thus Active First below is at 6 weeks after baseline, Washout is at 12 weeks, Active First then Sham at 18, and Active First then Sham Washout at 24 and the same pattern for the Sham First group.
Time frame: Up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active First | Tinnitus Hearing Survey | -0.7 score on a scale | Standard Deviation 0.4 |
| Active-First Washout | Tinnitus Hearing Survey | -1.8 score on a scale | Standard Deviation 0.4 |
| Active-First Then Sham | Tinnitus Hearing Survey | -0.9 score on a scale | Standard Deviation 0.5 |
| Active-First-Then-Sham Washout | Tinnitus Hearing Survey | -1.4 score on a scale | Standard Deviation 0.6 |
| Sham First | Tinnitus Hearing Survey | -0.2 score on a scale | Standard Deviation 0.4 |
| Sham-First Washout | Tinnitus Hearing Survey | -0.6 score on a scale | Standard Deviation 0.5 |
| Sham-First Then Active | Tinnitus Hearing Survey | -1.3 score on a scale | Standard Deviation 0.5 |
| Sham-First-Then-Active Washout | Tinnitus Hearing Survey | -1.5 score on a scale | Standard Deviation 0.6 |