Trial Outcomes & Findings for Reversing Synchronized Brain Circuits With Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts (NCT NCT03621735)

Last Updated: 2023-08-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

100 participants

Primary outcome timeframe

Up to 24 weeks

Results posted on

2023-08-30

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	50	50
Overall Study Received Device or Sham Device to Use	49	50
Overall Study Began First Washout Period	41	44
Overall Study Began Crossover Assignment	39	40
Overall Study Began Second Washout Period	39	39
Overall Study Began 12-Week Follow Up	38	39
Overall Study COMPLETED	37	37
Overall Study NOT COMPLETED	13	13

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Withdrawal by Subject	13	13

Baseline Characteristics

Reversing Synchronized Brain Circuits With Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Then Sham n=49 Participants 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.	Sham Then Active n=50 Participants 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.	Total n=99 Participants Total of all reporting groups
Age, Continuous	47.0 years STANDARD_DEVIATION 1.8 • n=5 Participants	47.1 years STANDARD_DEVIATION 1.8 • n=7 Participants	47.1 years STANDARD_DEVIATION 1.8 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	22 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	48 Participants n=7 Participants	96 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	45 Participants n=7 Participants	89 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	49 Participants n=5 Participants	50 Participants n=7 Participants	99 Participants n=5 Participants
Objective Tinnitus Loudness	57.0 decibels STANDARD_DEVIATION 13.7 • n=5 Participants	55.1 decibels STANDARD_DEVIATION 13.4 • n=7 Participants	56.1 decibels STANDARD_DEVIATION 13.5 • n=5 Participants
Tinnitus Functional Index (TFI)	43.1 score on a scale STANDARD_DEVIATION 13.4 • n=5 Participants	42.6 score on a scale STANDARD_DEVIATION 16.8 • n=7 Participants	42.9 score on a scale STANDARD_DEVIATION 15.1 • n=5 Participants
Tinnitus Handicap Inventory (THI)	37.9 score on a scale STANDARD_DEVIATION 17.7 • n=5 Participants	34.9 score on a scale STANDARD_DEVIATION 18.3 • n=7 Participants	36.4 score on a scale STANDARD_DEVIATION 18 • n=5 Participants
Minimum Masking Level (MML)	35.4 dB (sensation level) STANDARD_DEVIATION 12.9 • n=5 Participants	33.0 dB (sensation level) STANDARD_DEVIATION 12.2 • n=7 Participants	34.2 dB (sensation level) STANDARD_DEVIATION 12.6 • n=5 Participants
Tinnitus Hearing Survey	5.9 score on a scale STANDARD_DEVIATION 2.5 • n=5 Participants	5.2 score on a scale STANDARD_DEVIATION 3 • n=7 Participants	5.6 score on a scale STANDARD_DEVIATION 2.8 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active First n=41 Participants Participants who were assigned to the bimodal auditory-somatosensory stimulation (intervention) initially following randomization and completed treatment.	Active-First Washout n=40 Participants Participants who received the intervention initially following randomization and completed the first washout period.	Active-First Then Sham n=39 Participants Participants who initially received the intervention following randomization and completed treatment with the sham bimodal auditory-somatosensory stimulation (sham) following the first washout period.	Active-First-Then-Sham Washout n=39 Participants Participants who completed the second washout after initially receiving the intervention following randomization and then received the sham following the first washout period.	Sham First n=44 Participants Participants who were assigned to the sham bimodal auditory-somatosensory stimulation (sham) initially following randomization and completed treatment.	Sham-First Washout n=40 Participants Participants who received the sham initially following randomization and completed the first washout period.	Sham-First Then Active n=39 Participants Participants who initially received the sham following randomization and completed treatment with the bimodal auditory-somatosensory stimulation (intervention) following the first washout period.	Sham-First-Then-Active Washout n=38 Participants Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First-Then-Active Washout Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First Post-Study Monitoring (PSM) Period Participants who received the sham initially following randomization, and who completed the follow-up period.
Change in Objective Tinnitus Loudness	-6.1 decibels sensation level (dB SL) Standard Error 1.8	-9.5 decibels sensation level (dB SL) Standard Error 2.1	-10.2 decibels sensation level (dB SL) Standard Error 2.3	-11.0 decibels sensation level (dB SL) Standard Error 2.5	-3.7 decibels sensation level (dB SL) Standard Error 1.3	-4.7 decibels sensation level (dB SL) Standard Error 1.5	-5.8 decibels sensation level (dB SL) Standard Error 2.3	-4.9 decibels sensation level (dB SL) Standard Error 2.4	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active First n=41 Participants Participants who were assigned to the bimodal auditory-somatosensory stimulation (intervention) initially following randomization and completed treatment.	Active-First Washout n=40 Participants Participants who received the intervention initially following randomization and completed the first washout period.	Active-First Then Sham n=39 Participants Participants who initially received the intervention following randomization and completed treatment with the sham bimodal auditory-somatosensory stimulation (sham) following the first washout period.	Active-First-Then-Sham Washout n=39 Participants Participants who completed the second washout after initially receiving the intervention following randomization and then received the sham following the first washout period.	Sham First n=37 Participants Participants who were assigned to the sham bimodal auditory-somatosensory stimulation (sham) initially following randomization and completed treatment.	Sham-First Washout n=44 Participants Participants who received the sham initially following randomization and completed the first washout period.	Sham-First Then Active n=40 Participants Participants who initially received the sham following randomization and completed treatment with the bimodal auditory-somatosensory stimulation (intervention) following the first washout period.	Sham-First-Then-Active Washout n=39 Participants Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First-Then-Active Washout n=38 Participants Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First Post-Study Monitoring (PSM) Period n=37 Participants Participants who received the sham initially following randomization, and who completed the follow-up period.
Change in Tinnitus Functional Index (TFI)	-12.0 Points on a Scale Standard Error 2.3	-13.1 Points on a Scale Standard Error 2.4	-16.8 Points on a Scale Standard Error 2.4	-15.9 Points on a Scale Standard Error 2.0	-12.1 Points on a Scale Standard Error 2.7	-6.5 Points on a Scale Standard Error 1.9	-8.3 Points on a Scale Standard Error 2.0	-13.8 Points on a Scale Standard Error 2.7	-13.4 Points on a Scale Standard Error 2.8	-15.3 Points on a Scale Standard Error 2.6

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active First n=41 Participants Participants who were assigned to the bimodal auditory-somatosensory stimulation (intervention) initially following randomization and completed treatment.	Active-First Washout n=40 Participants Participants who received the intervention initially following randomization and completed the first washout period.	Active-First Then Sham n=39 Participants Participants who initially received the intervention following randomization and completed treatment with the sham bimodal auditory-somatosensory stimulation (sham) following the first washout period.	Active-First-Then-Sham Washout n=39 Participants Participants who completed the second washout after initially receiving the intervention following randomization and then received the sham following the first washout period.	Sham First n=44 Participants Participants who were assigned to the sham bimodal auditory-somatosensory stimulation (sham) initially following randomization and completed treatment.	Sham-First Washout n=40 Participants Participants who received the sham initially following randomization and completed the first washout period.	Sham-First Then Active n=39 Participants Participants who initially received the sham following randomization and completed treatment with the bimodal auditory-somatosensory stimulation (intervention) following the first washout period.	Sham-First-Then-Active Washout n=38 Participants Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First-Then-Active Washout Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First Post-Study Monitoring (PSM) Period Participants who received the sham initially following randomization, and who completed the follow-up period.
Tinnitus Handicap Inventory (THI)	-5.8 Points on a Scale Standard Error 2.1	-6.4 Points on a Scale Standard Error 1.9	-8.0 Points on a Scale Standard Error 2.6	-6.9 Points on a Scale Standard Error 2.0	-1.6 Points on a Scale Standard Error 1.5	-2.2 Points on a Scale Standard Error 1.7	-5.3 Points on a Scale Standard Error 2.8	-4.6 Points on a Scale Standard Error 2.7	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active First n=41 Participants Participants who were assigned to the bimodal auditory-somatosensory stimulation (intervention) initially following randomization and completed treatment.	Active-First Washout n=40 Participants Participants who received the intervention initially following randomization and completed the first washout period.	Active-First Then Sham n=39 Participants Participants who initially received the intervention following randomization and completed treatment with the sham bimodal auditory-somatosensory stimulation (sham) following the first washout period.	Active-First-Then-Sham Washout n=39 Participants Participants who completed the second washout after initially receiving the intervention following randomization and then received the sham following the first washout period.	Sham First n=44 Participants Participants who were assigned to the sham bimodal auditory-somatosensory stimulation (sham) initially following randomization and completed treatment.	Sham-First Washout n=40 Participants Participants who received the sham initially following randomization and completed the first washout period.	Sham-First Then Active n=39 Participants Participants who initially received the sham following randomization and completed treatment with the bimodal auditory-somatosensory stimulation (intervention) following the first washout period.	Sham-First-Then-Active Washout n=38 Participants Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First-Then-Active Washout Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First Post-Study Monitoring (PSM) Period Participants who received the sham initially following randomization, and who completed the follow-up period.
Change in Tinnitus Bandwidth/Spectrum (TinnTester Interactive Software)	7.1 units on a scale Standard Error 0.9	8.4 units on a scale Standard Error 1.0	9.5 units on a scale Standard Error 1.0	10.3 units on a scale Standard Error 1.2	8.0 units on a scale Standard Error 0.9	8.5 units on a scale Standard Error 1.0	10.3 units on a scale Standard Error 1.4	11.0 units on a scale Standard Error 1.5	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active First n=41 Participants Participants who were assigned to the bimodal auditory-somatosensory stimulation (intervention) initially following randomization and completed treatment.	Active-First Washout n=40 Participants Participants who received the intervention initially following randomization and completed the first washout period.	Active-First Then Sham n=39 Participants Participants who initially received the intervention following randomization and completed treatment with the sham bimodal auditory-somatosensory stimulation (sham) following the first washout period.	Active-First-Then-Sham Washout n=39 Participants Participants who completed the second washout after initially receiving the intervention following randomization and then received the sham following the first washout period.	Sham First n=44 Participants Participants who were assigned to the sham bimodal auditory-somatosensory stimulation (sham) initially following randomization and completed treatment.	Sham-First Washout n=40 Participants Participants who received the sham initially following randomization and completed the first washout period.	Sham-First Then Active n=39 Participants Participants who initially received the sham following randomization and completed treatment with the bimodal auditory-somatosensory stimulation (intervention) following the first washout period.	Sham-First-Then-Active Washout n=38 Participants Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First-Then-Active Washout Participants who completed the second washout after initially receiving the sham following randomization and then received the intervention following the first washout period.	Sham-First Post-Study Monitoring (PSM) Period Participants who received the sham initially following randomization, and who completed the follow-up period.
Changes in Minimum Masking Level (MML)	-5.1 dB (sensation level) Standard Deviation 2.3	-1.1 dB (sensation level) Standard Deviation 2.3	-2.0 dB (sensation level) Standard Deviation 2.9	0.2 dB (sensation level) Standard Deviation 2.0	-2.7 dB (sensation level) Standard Deviation 1.6	-1.6 dB (sensation level) Standard Deviation 1.5	0.0 dB (sensation level) Standard Deviation 2.1	-0.1 dB (sensation level) Standard Deviation 3.3	—	—

SECONDARY outcome

Timeframe: 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.