Trial Outcomes & Findings for Effect of rTMS on Resting State Brain Activity in Tinnitus (NCT NCT00926237)

Last Updated: 2020-11-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

58 participants

Primary outcome timeframe

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).

Results posted on

2020-11-20

Participant Flow

A total of 58 participants were enrolled. Recruitment used a waitlist of subjects who already expressed interest in tinnitus studies and from advertisement.

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.

Participant milestones

Participant milestones
Measure	Sham Followed by Active 1Hz Then 10Hz rTMS Subjects assigned to this arm received sham rTMS followed by active rTMS at 1Hz and then active rTMS at 10 Hz. Each treatment consisted of a four-day trial with no less than 21 days separating each condition. Subjects receive sham stimulation first to prevent carry forward effects of the active treatment condition into the sham condition. Sham rTMS Active 1 Hz rTMS Active 1 Hz rTMS	Sham Followed by Active 10Hz Then 1Hz rTMS Subjects assigned to this arm received sham rTMS followed by active rTMS at 10 Hz and then active rTMS at 1 Hz. Each treatment consisted of a four-day trial with no less than 21 days separating each condition. Subjects receive sham stimulation first to prevent carry forward effects of the active treatment condition into the sham condition. Sham rTMS Active 1 Hz rTMS Active 10 Hz rTMS
Overall Study STARTED	19	20
Overall Study COMPLETED	17	19
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sham Followed by Active 1Hz Then 10Hz rTMS Subjects assigned to this arm received sham rTMS followed by active rTMS at 1Hz and then active rTMS at 10 Hz. Each treatment consisted of a four-day trial with no less than 21 days separating each condition. Subjects receive sham stimulation first to prevent carry forward effects of the active treatment condition into the sham condition. Sham rTMS Active 1 Hz rTMS Active 1 Hz rTMS	Sham Followed by Active 10Hz Then 1Hz rTMS Subjects assigned to this arm received sham rTMS followed by active rTMS at 10 Hz and then active rTMS at 1 Hz. Each treatment consisted of a four-day trial with no less than 21 days separating each condition. Subjects receive sham stimulation first to prevent carry forward effects of the active treatment condition into the sham condition. Sham rTMS Active 1 Hz rTMS Active 10 Hz rTMS
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Baseline ratings are reported only for the 39 subjects who were assigned to a treatment arm and completed all baseline assessments

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Subjects Enrolled in the Study n=58 Participants Baseline information is reported for all subjects enrolled.
Age, Continuous	55 years STANDARD_DEVIATION 12.2 • n=58 Participants
Sex: Female, Male Female	11 Participants n=58 Participants
Sex: Female, Male Male	47 Participants n=58 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=58 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants n=58 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=58 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=58 Participants
Race (NIH/OMB) Asian	0 Participants n=58 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=58 Participants
Race (NIH/OMB) Black or African American	0 Participants n=58 Participants
Race (NIH/OMB) White	56 Participants n=58 Participants
Race (NIH/OMB) More than one race	1 Participants n=58 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=58 Participants
Baseline analogue ratings of tinnitus awareness	58.72 units on a scale STANDARD_DEVIATION 22.56 • n=39 Participants • Baseline ratings are reported only for the 39 subjects who were assigned to a treatment arm and completed all baseline assessments

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sham rTMS n=36 Participants This comparison examined change in analogue ratings of tinnitus awareness between the baseline and the sham rTMS treatment condition.	Sham Washout n=36 Participants This comparison examined change in analogue ratings of tinnitus awareness between baseline and the sham washout period of 21 days.	1 Hz Active rTMS n=36 Participants This comparison examined change in analogue ratings of tinnitus awareness between the baseline and the 1 Hz active rTMS condition.	1 Hz Washout n=36 Participants This comparison examined change in analogue ratings of tinnitus awareness between baseline and the 1 Hz washout period lasting 21 days.	10 Hz Active rTMS n=36 Participants This comparison examined change in analogue ratings of tinnitus awareness between the baseline and the 10 Hz active rTMS condition.	10 Hz Washout n=36 Participants This comparison examined change in analogue ratings of tinnitus awareness between baseline and the 10 Hz washout period of 21 days.
Change From Baseline on the Analogue Rating of Tinnitus Awareness.	-4.08 units on a scale Standard Error 3.72	-4.70 units on a scale Standard Error 3.90	-9.82 units on a scale Standard Error 3.72	-9.89 units on a scale Standard Error 3.91	-10.85 units on a scale Standard Error 3.85	-9.43 units on a scale Standard Error 4.06

Adverse Events

Subjects Who Received Sham Followed by Active 1 Hz rTMS Then Active 10 Hz rTMS.

Serious events: 1 serious events

Other events: 12 other events

Deaths: 1 deaths

Subjects Who Received Sham Followed by Active 10 Hz rTMS Then Active 1 Hz rTMS

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Subjects Who Received Sham Followed by Active 1 Hz rTMS Then Active 10 Hz rTMS. n=27 participants at risk Subjects in this arm received a course of sham stimulation which was followed by a course of active stimulation at 1 Hz rTMS and then a course of active stimulation at 10 Hz.	Subjects Who Received Sham Followed by Active 10 Hz rTMS Then Active 1 Hz rTMS n=31 participants at risk Subjects in this arm received a course of sham stimulation which was followed by a course of active stimulation at 10 Hz rTMS and then a course of active stimulation at 1 Hz.
Cardiac disorders Death	3.7% 1/27 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.	0.00% 0/31 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.

Other adverse events

Other adverse events
Measure	Subjects Who Received Sham Followed by Active 1 Hz rTMS Then Active 10 Hz rTMS. n=27 participants at risk Subjects in this arm received a course of sham stimulation which was followed by a course of active stimulation at 1 Hz rTMS and then a course of active stimulation at 10 Hz.	Subjects Who Received Sham Followed by Active 10 Hz rTMS Then Active 1 Hz rTMS n=31 participants at risk Subjects in this arm received a course of sham stimulation which was followed by a course of active stimulation at 10 Hz rTMS and then a course of active stimulation at 1 Hz.
Skin and subcutaneous tissue disorders Headache	14.8% 4/27 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.	12.9% 4/31 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.
Musculoskeletal and connective tissue disorders Jaw pain	11.1% 3/27 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.	3.2% 1/31 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.
Nervous system disorders Tinnitus increase	3.7% 1/27 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.	0.00% 0/31 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.
General disorders Illness	40.7% 11/27 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.	22.6% 7/31 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.
Eye disorders eye muscle twitching	0.00% 0/27 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.	6.5% 2/31 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.
Cardiac disorders Increase heart rate	3.7% 1/27 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.	0.00% 0/31 • Adverse event data were collected from baseline until study completion at followup: ~113 days for participants who did not enter maintenance and up to ~159 days for subjects who entered maintenance. While it was possible to accurately report Adverse Events by assigned Arm, it was not possible to accurately report adverse events by rTMS frequency because the majority of adverse events (49/58) were not study related. Rather they included illness or injuries that occurred outside the study in daily life. Only 9/58 adverse events were coded as study related and these are described in the Adverse Event Additional Description field.

Additional Information

Dr Mark Mennemeier

University of Arkansas for Medical Sciences

Phone: 205 410 2413

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place