Tinnitus
Conditions
Keywords
Tinnitus, Medical Device, Randomized, Vagus Nerve Stimulation
Brief summary
Assess the safety and efficacy of VNS paired with tones for tinnitus using a randomized, controlled, parallel study design.
Detailed description
Patients who have moderate to severe tinnitus, at least one year post diagnosis, may enroll. All patients will be implanted and randomized to one of two groups: * a group receiving VNS paired with tones and; * a group that receives VNS and tones, but with different settings. After device use training, therapy is delivered at home by the patient for 6 weeks. Patients have eight baseline audiometric assessments along with two questionnaire assessments, an assessment after recovery before treatment starts, and tinnitus assessments every two weeks during therapy through the 6 week randomized portion of the study. After the randomized portion, all patients receive VNS paired with tones. Patients will continue to return for quarterly visits and tinnitus assessments through the first year after implant, regardless of their therapy status. Interested patients can continue to receive longer-term treatment after the first year. A goal of up to 30 patients enrolled and implanted across four sites is planned for this study.
Interventions
DEVICEVNS Treatment
VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.
DEVICEVNS Control
This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Sponsors
National Institute on Deafness and Other Communication Disorders (NIDCD)
MicroTransponder Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 22 to 65 years of age 2. Have been diagnosed as suffering from sensorineural tinnitus and at least some tonal quality of the tinnitus 3. Unilateral or bilateral tinnitus 4. Have experienced tinnitus for at least one year and failed at least one tinnitus therapy (such as a counseling or sound therapy procedure. The diagnosis of tinnitus will include an audiological or medical diagnosis in their health records, as well as a patient affirmation of tinnitus greater than 12 months 5. MML \>= 7 dB (decibel) 6. Have tinnitus score of 40 or greater on the Tinnitus Handicap Questionnaire; (THQ) 7. No tinnitus treatment for at least 4 weeks prior to study entry. 8. Willing and able to understand and comply with all study-related procedures during the course of the study
Exclusion criteria
1. Acute or intermittent tinnitus 2. Severe hearing loss in any ear, as defined as more than an 80 dB HL (decibels hearing level) at frequencies from 250 Hz. to 8,000 Hz. 3. Meniere's disease, ear tumors, or evidence of active middle ear disease (such as fluid, infection, tumor, mass) 4. Any other implanted device such as a pacemaker or other neurostimulator; any other investigational device or drug 5. Pregnant or plan on becoming pregnant or breastfeeding during the study period 6. Currently require, or likely to require, MRI or diathermy during the study duration 7. History of adverse reactions to anesthetics (e.g., lidocaine) that in the Investigator's opinion make surgery too risky 8. Beck Depression Inventory (BDI) of 30 or greater 9. Any other form of tinnitus treatments (e.g. Herbal medication, acupuncture or chiropractic medicine) are not allowed during the study. 10. Any drug known to mimic, increase or decrease release or removal of a diffuse neuromodulator, such as norepinephrine, dopamine, serotonin, benzodiazepines, and acetylcholine is not allowed, as well as any psychoactive medications. 11. Significant cardiac history 12. Use of any medication known to cause or increase tinnitus, such as NSAIDS (ibuprofen, naproxen, nabumetone, etc.), aspirin and other salicylates, furosemide (Lasix) and other loop diuretics, mycin antibiotics such as vancomycin, quinine and related drugs, and chemotherapy agents such as cisplatin. 13. Involvement in litigation (e.g., worker's compensation claim and/or receiving disability benefits related to tinnitus and/or hearing loss).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | 6-weeks | Assess the number of serious adverse events during the study, and compare between groups to indicate if there are more in the treatment group than the control group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 6-weeks | Assess the number of adverse events during the study, and compare between groups to indicate if there are more in the treatment group than the control group. |
| Change in Minimum Masking Level (MML) in Units of dB (Decibels) | 6-weeks (pre-implant to after 6-weeks of VNS) | Asses the change in minimum masking level (MML) for both groups and compare between the groups. |
| Percent Change in Tinnitus Handicap Inventory (THI) | 6-weeks (pre-implant to after 6-weeks of VNS) | Assess the change in THI score for both groups and compare between the groups. The THI is a questionnaire that asks subjects to assess their perception of their tinnitus by rating each question as a Yes (4 points), No (0 points) or Sometimes (2 points). There are 25 questions, scores are summed, so the scale ranges from 0 to 100. Scores are graded as: Grade 1 - Slight (0-16) Only heard in a quiet environment; Grade 2 - Mild (18-36) Easily masked by environmental sounds and easily forgotten with activities.; Grade 3 - Moderate (38-56) Noticed in presence of background noise, although daily activities can still be performed.; Grade 4 - Severe (58-76) Almost always heard, leads to disturbed sleep patterns and can interfere with daily activities.; Grade 5 - Catastrophic (78-100) Always heard, disturbed sleep patterns, difficulty with any activities. |
| Change in Tinnitus Handicap Questionnaire (THQ) | 6-weeks (pre-implant to after 6-weeks of VNS) | Assess the change in THQ score for both groups and compare between the groups. The THQ is a patient questionnaire with 27 questions with each question having a score from 1 to 100. Scoring includes three factors - Factor 1 (Social, Emotional, Behavioral), Factor 2 (Tinnitus and Hearing), Factor 3 (Outlook). Fifteen questions are included in Factor 1, 8 questions in Factor 2, and 4 questions in Factor 3. A total score is calculated by adding the scores for Factor 1 questions and multiplying by 15/27, adding the scores for Factor 2 and multiplying by 8/27, and adding the scores for Factor 3 and multiplying by 4/27. This is then summed for the total score. Total score ranges from 0 to 100, with higher scores indicating more severe tinnitus. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Tinnitus Functional Index (TFI) | 6-weeks (pre-implant to after 6-weeks of VNS) | Assess the change in TFI score for both groups and compare between the groups. The TFI has eight subscales that address the intrusiveness of tinnitus, the sense of control the patient has, cognitive interference, sleep disturbance, auditory issues, relaxation issues, quality of life, and emotional distress. There are a total of 25 questions, with a range of 0 to 10 on each item (0 to 250) total. All valid answers are summed, divided by the number of questions which were answered, and multiplied by 10 (0-100 range). Score range from 0 to 100 with higher scores indicating worse tinnitus. |
Countries
United States
Participant flow
Recruitment details
Sixty-two subjects were screened for inclusion into the study. Nine (9) did not meet inclusion criteria, 15 declined to participate, 3 had medical issues, and 5 were screened but were after the study limit of 30. Thirty subjects were enrolled and implanted with the study device.
Participants by arm
| Arm | Count |
|---|---|
| VNS Treatment Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period.
VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS. | 16 |
| VNS Control Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained.
VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective. | 14 |
| Total | 30 |
Baseline characteristics
| Characteristic | VNS Treatment | Total | VNS Control |
|---|---|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 7.6 | 55.6 years STANDARD_DEVIATION 8.4 | 54.9 years STANDARD_DEVIATION 9.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 16 Participants | 30 Participants | 14 Participants |
| Region of Enrollment United States | 16 participants | 30 participants | 14 participants |
| Sex: Female, Male Female | 1 Participants | 11 Participants | 10 Participants |
| Sex: Female, Male Male | 15 Participants | 19 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 16 | 1 / 14 |
| serious Total, serious adverse events | 1 / 16 | 2 / 14 |
Outcome results
Primary
Number of Participants With Serious Adverse Events
Assess the number of serious adverse events during the study, and compare between groups to indicate if there are more in the treatment group than the control group.
Time frame: 6-weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS Treatment | Number of Participants With Serious Adverse Events | 1 participants |
| VNS Control | Number of Participants With Serious Adverse Events | 2 participants |
Secondary
Change in Minimum Masking Level (MML) in Units of dB (Decibels)
Asses the change in minimum masking level (MML) for both groups and compare between the groups.
Time frame: 6-weeks (pre-implant to after 6-weeks of VNS)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VNS Treatment | Change in Minimum Masking Level (MML) in Units of dB (Decibels) | 3.5 dB (decibels) |
| VNS Control | Change in Minimum Masking Level (MML) in Units of dB (Decibels) | -3.8 dB (decibels) |
Secondary
Change in Tinnitus Handicap Questionnaire (THQ)
Assess the change in THQ score for both groups and compare between the groups. The THQ is a patient questionnaire with 27 questions with each question having a score from 1 to 100. Scoring includes three factors - Factor 1 (Social, Emotional, Behavioral), Factor 2 (Tinnitus and Hearing), Factor 3 (Outlook). Fifteen questions are included in Factor 1, 8 questions in Factor 2, and 4 questions in Factor 3. A total score is calculated by adding the scores for Factor 1 questions and multiplying by 15/27, adding the scores for Factor 2 and multiplying by 8/27, and adding the scores for Factor 3 and multiplying by 4/27. This is then summed for the total score. Total score ranges from 0 to 100, with higher scores indicating more severe tinnitus.
Time frame: 6-weeks (pre-implant to after 6-weeks of VNS)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VNS Treatment | Change in Tinnitus Handicap Questionnaire (THQ) | -2.5 units on a scale |
| VNS Control | Change in Tinnitus Handicap Questionnaire (THQ) | -7.5 units on a scale |
Secondary
Number of Participants With Adverse Events
Assess the number of adverse events during the study, and compare between groups to indicate if there are more in the treatment group than the control group.
Time frame: 6-weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VNS Treatment | Number of Participants With Adverse Events | 11 participants |
| VNS Control | Number of Participants With Adverse Events | 9 participants |
Secondary
Percent Change in Tinnitus Handicap Inventory (THI)
Assess the change in THI score for both groups and compare between the groups. The THI is a questionnaire that asks subjects to assess their perception of their tinnitus by rating each question as a Yes (4 points), No (0 points) or Sometimes (2 points). There are 25 questions, scores are summed, so the scale ranges from 0 to 100. Scores are graded as: Grade 1 - Slight (0-16) Only heard in a quiet environment; Grade 2 - Mild (18-36) Easily masked by environmental sounds and easily forgotten with activities.; Grade 3 - Moderate (38-56) Noticed in presence of background noise, although daily activities can still be performed.; Grade 4 - Severe (58-76) Almost always heard, leads to disturbed sleep patterns and can interfere with daily activities.; Grade 5 - Catastrophic (78-100) Always heard, disturbed sleep patterns, difficulty with any activities.
Time frame: 6-weeks (pre-implant to after 6-weeks of VNS)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VNS Treatment | Percent Change in Tinnitus Handicap Inventory (THI) | -17.7 percentage change of THI |
| VNS Control | Percent Change in Tinnitus Handicap Inventory (THI) | -7.3 percentage change of THI |
Other Pre-specified
Change in Tinnitus Functional Index (TFI)
Assess the change in TFI score for both groups and compare between the groups. The TFI has eight subscales that address the intrusiveness of tinnitus, the sense of control the patient has, cognitive interference, sleep disturbance, auditory issues, relaxation issues, quality of life, and emotional distress. There are a total of 25 questions, with a range of 0 to 10 on each item (0 to 250) total. All valid answers are summed, divided by the number of questions which were answered, and multiplied by 10 (0-100 range). Score range from 0 to 100 with higher scores indicating worse tinnitus.
Time frame: 6-weeks (pre-implant to after 6-weeks of VNS)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| VNS Treatment | Change in Tinnitus Functional Index (TFI) | -2.03 units on a scale |
| VNS Control | Change in Tinnitus Functional Index (TFI) | -7.5 units on a scale |