Trial Outcomes & Findings for Collaborative Tinnitus Research at Washington University (NCT NCT00567892)
NCT ID: NCT00567892
Last Updated: 2018-11-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
55 participants
Primary outcome timeframe
baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks)
Results posted on
2018-11-16
Participant Flow
Enrollment period: August, 2008 to June, 2010
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.
Participant milestones
| Measure |
Active Then Sham rTMS Treatment (2 Weeks)
Active rTMS Treatment for 2 weeks followed by 2 weeks wash-out and then 2 weeks sham. Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.
|
Sham Then Active rTMS Treatment (2 Weeks)
Sham treatment for 2 weeks followed by 2 weeks wash-out and then 2 weeks Active rTMS Treatment.Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.
|
Active Then Sham rTMS Treatment (4 Weeks)
Active rTMS Treatment for 4 weeks followed by 2 weeks wash-out and then 4 weeks sham.Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.One subject had a drop of THI larger than 20 points from baseline after first arm of treatment and did not get the second arm.
|
Sham Then Active rTMS Treatment (4 Weeks)
Sham treatment for 4 weeks followed by 2 weeks wash-out and then 4 weeks Active rTMS Treatment. Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.
|
|---|---|---|---|---|
|
First Treatment (2 or 4 Weeks)
STARTED
|
7
|
7
|
10
|
10
|
|
First Treatment (2 or 4 Weeks)
COMPLETED
|
7
|
7
|
9
|
6
|
|
First Treatment (2 or 4 Weeks)
NOT COMPLETED
|
0
|
0
|
1
|
4
|
|
Washout (2 Weeks)
STARTED
|
7
|
7
|
9
|
6
|
|
Washout (2 Weeks)
COMPLETED
|
7
|
7
|
9
|
6
|
|
Washout (2 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Treatment (2 or 4 Weeks)
STARTED
|
7
|
7
|
9
|
6
|
|
Second Treatment (2 or 4 Weeks)
COMPLETED
|
7
|
7
|
9
|
5
|
|
Second Treatment (2 or 4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Active Then Sham rTMS Treatment (2 Weeks)
Active rTMS Treatment for 2 weeks followed by 2 weeks wash-out and then 2 weeks sham. Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.
|
Sham Then Active rTMS Treatment (2 Weeks)
Sham treatment for 2 weeks followed by 2 weeks wash-out and then 2 weeks Active rTMS Treatment.Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.
|
Active Then Sham rTMS Treatment (4 Weeks)
Active rTMS Treatment for 4 weeks followed by 2 weeks wash-out and then 4 weeks sham.Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.One subject had a drop of THI larger than 20 points from baseline after first arm of treatment and did not get the second arm.
|
Sham Then Active rTMS Treatment (4 Weeks)
Sham treatment for 4 weeks followed by 2 weeks wash-out and then 4 weeks Active rTMS Treatment. Subjects who do not return to within 20 points of Baseline THI at the end of 2 weeks washout will have washout extended up to 2 additional 2-week washout-periods.At the end of 6 weeks total washout, if the subject's THI remains greater than 20 points difference from bsseline THI subject will be considered to have completed the study and will not complete the second cross study arm. Subject will go staight to end of study visit.
|
|---|---|---|---|---|
|
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
Collaborative Tinnitus Research at Washington University
Baseline characteristics by cohort
| Measure |
2 Week Treatment
n=14 Participants
Treatment (either active rTMS or sham)for 2 weeks followed by 2 week wash-out then treatment (opposite of first assignment)for 2 weeks
|
4 Week Treatment
n=20 Participants
Treatment (either active rTMS or sham)for 4 weeks followed by 2 week wash-out then treatment (opposite of first assignment)for 4 weeks
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
52 years
FULL_RANGE 5.1 • n=5 Participants
|
42 years
n=7 Participants
|
50 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
20 participants
n=7 Participants
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
2-weeks rTMS Active Treatment
n=14 Participants
Daily rTMS for about 1 hour with active device settings (stimulation intensity at 110% of motor threshold), for 2 weeks.
|
2-Weeks Sham rTMS Treatment
n=14 Participants
Daily sham-rTMS for about 1 hour with sham device settings for 2 weeks.
|
4-weeks rTMS Active Treatment
n=13 Participants
Daily rTMS for about 1 hour with active device settings (stimulation intensity at 110% of motor threshold), for 4 weeks.
|
4-weeks rTMS Sham Treatment
n=13 Participants
Daily sham-rTMS for about 1 hour with sham device settings for 4 weeks.
|
|---|---|---|---|---|
|
Change in THI (Tinnitus Handicap Inventory)
|
-5 units on a scale
Interval -14.0 to 0.0
|
-6 units on a scale
Interval -12.0 to -2.0
|
-10 units on a scale
Interval -12.0 to 3.0
|
-6 units on a scale
Interval -12.0 to 4.0
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
2-weeks rTMS Active Treatment
n=14 Participants
Daily rTMS for about 1 hour with active device settings (stimulation intensity at 110% of motor threshold), for 2 weeks.
|
2-Weeks Sham rTMS Treatment
n=14 Participants
Daily sham-rTMS for about 1 hour with sham device settings for 2 weeks.
|
4-weeks rTMS Active Treatment
n=13 Participants
Daily rTMS for about 1 hour with active device settings (stimulation intensity at 110% of motor threshold), for 4 weeks.
|
4-weeks rTMS Sham Treatment
n=13 Participants
Daily sham-rTMS for about 1 hour with sham device settings for 4 weeks.
|
|---|---|---|---|---|
|
Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater
|
1 participants
|
3 participants
|
3 participants
|
5 participants
|
Adverse Events
2 Weeks Treatment
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Four Week Treatment
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
2 Weeks Treatment
n=14 participants at risk
Treatment (either active rTMS or sham) for two weeks followed by 2 weeks wash-out then treatment (opposite of first assignment)for two weeks
|
Four Week Treatment
n=20 participants at risk
Treatment (either active rTMS or sham)for 4 weeks followed by 2 week wash-out then treatment (opposite of first assignment)for 4 weeks
|
|---|---|---|
|
Ear and labyrinth disorders
Worsening of Tinnitus
|
14.3%
2/14 • Number of events 4 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
5.0%
1/20 • Number of events 1 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
|
Ear and labyrinth disorders
Ear Pain
|
7.1%
1/14 • Number of events 1 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
5.0%
1/20 • Number of events 2 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
|
Reproductive system and breast disorders
Worsening of Menopausal Symptoms
|
25.0%
1/4 • Number of events 10 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
0.00%
0/7 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
|
Musculoskeletal and connective tissue disorders
Neck Stiffness or Pain
|
21.4%
3/14 • Number of events 7 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
5.0%
1/20 • Number of events 1 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
|
Nervous system disorders
Lightheaded feeling
|
7.1%
1/14 • Number of events 2 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
0.00%
0/20 • Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.
Subjects who had decrease in THI \> 20 pts were followed for up to 6 months. All subjects were followed thru for 4 weeks post treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place