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Effect of rTMS on Resting State Brain Activity in Tinnitus

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ClinicalTrials.gov Identifier: NCT00926237
Recruitment Status : Completed
First Posted : June 23, 2009
Results First Posted : November 20, 2020
Last Update Posted : November 20, 2020
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
University of Arkansas

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Condition Tinnitus
Interventions Device: Sham rTMS - Sham repetitive transcranial magnetic stimulation
Device: Active 1 Hz rTMS - Active repetitive transcranial magnetic stimulation delivered at 1 Hz frequency
Device: Active 10 Hz rTMS - active repetitive transcranial magnetic stimulation delivered at 10 Hz frequency
Enrollment 58
Recruitment Details A total of 58 participants were enrolled. Recruitment used a waitlist of subjects who already expressed interest in tinnitus studies and from advertisement.
Pre-assignment Details 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.
Arm/Group Title Sham Followed by Active 1Hz Then 10Hz rTMS Sham Followed by Active 10Hz Then 1Hz rTMS
Hide Arm/Group Description

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

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

Period Title: Overall Study
Started 19 [1] 20 [2]
Completed 17 19
Not Completed 2 1
Reason Not Completed
Withdrawal by Subject             2             1
[1]
Two subjects withdrew after receiving sham rTMS but before receiving active rTMS.
[2]
One subjects withdrew after receiving sham rTMS but before receiving active rTMS.
Arm/Group Title All Subjects Enrolled in the Study
Hide Arm/Group Description Baseline information is reported for all subjects enrolled.
Overall Number of Baseline Participants 58
Hide Baseline Analysis Population Description
Numbers are reported for all persons enrolled in the study, not just those for subjects who were assigned to a treatment arm.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants
55  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants
Female
11
  19.0%
Male
47
  81.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants
Hispanic or Latino
2
   3.4%
Not Hispanic or Latino
55
  94.8%
Unknown or Not Reported
1
   1.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants
American Indian or Alaska Native
1
   1.7%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
56
  96.6%
More than one race
1
   1.7%
Unknown or Not Reported
0
   0.0%
Baseline analogue ratings of tinnitus awareness   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 39 participants
58.72  (22.56)
[1]
Measure Description: Baseline ratings are the average of the baseline assessments on separate days. Analogue ratings of tinnitus awareness range from 0 (no tinnitus) to 100 (painfully loud tinnitus).
[2]
Measure Analysis Population Description: Baseline ratings are reported only for the 39 subjects who were assigned to a treatment arm and completed all baseline assessments
1.Primary Outcome
Title Change From Baseline on the Analogue Rating of Tinnitus Awareness.
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Sham rTMS Sham Washout 1 Hz Active rTMS 1 Hz Washout 10 Hz Active rTMS 10 Hz Washout
Hide Arm/Group Description:
This comparison examined change in analogue ratings of tinnitus awareness between the baseline and the sham rTMS treatment condition.
This comparison examined change in analogue ratings of tinnitus awareness between baseline and the sham washout period of 21 days.
This comparison examined change in analogue ratings of tinnitus awareness between the baseline and the 1 Hz active rTMS condition.
This comparison examined change in analogue ratings of tinnitus awareness between baseline and the 1 Hz washout period lasting 21 days.
This comparison examined change in analogue ratings of tinnitus awareness between the baseline and the 10 Hz active rTMS condition.
This comparison examined change in analogue ratings of tinnitus awareness between baseline and the 10 Hz washout period of 21 days.
Overall Number of Participants Analyzed 36 36 36 36 36 36
Mean (Standard Error)
Unit of Measure: units on a scale
-4.08  (3.72) -4.70  (3.90) -9.82  (3.72) -9.89  (3.91) -10.85  (3.85) -9.43  (4.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sham rTMS, 1 Hz Active rTMS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .04
Comments t value = -1.40
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.74
Estimation Comments 1Hz active rTMS - Sham rTMS
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sham rTMS, 10 Hz Active rTMS
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .02
Comments t value = -2.03
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.77
Estimation Comments 10 Hz active rTMS - Sham rTMS
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sham Washout, 10 Hz Washout
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .20
Comments t value = -1..28
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.73
Estimation Comments 10 Hz washout - sham washout period
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sham Washout, 1 Hz Washout
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .19
Comments t value = -1.29
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.19
Estimation Comments 1Hz washout - sham washout
Time Frame 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Subjects Who Received Sham Followed by Active 1 Hz rTMS Then Active 10 Hz rTMS. Subjects Who Received Sham Followed by Active 10 Hz rTMS Then Active 1 Hz rTMS
Hide Arm/Group Description 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 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.
All-Cause Mortality
Subjects Who Received Sham Followed by Active 1 Hz rTMS Then Active 10 Hz rTMS. Subjects Who Received Sham Followed by Active 10 Hz rTMS Then Active 1 Hz rTMS
Affected / at Risk (%) Affected / at Risk (%)
Total   1/27 (3.70%)   0/31 (0.00%) 
Hide Serious Adverse Events
Subjects Who Received Sham Followed by Active 1 Hz rTMS Then Active 10 Hz rTMS. Subjects Who Received Sham Followed by Active 10 Hz rTMS Then Active 1 Hz rTMS
Affected / at Risk (%) Affected / at Risk (%)
Total   1/27 (3.70%)   0/31 (0.00%) 
Cardiac disorders     
Death  [1]  1/27 (3.70%)  0/31 (0.00%) 
Indicates events were collected by systematic assessment
[1]
Drowning. Not study related.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Subjects Who Received Sham Followed by Active 1 Hz rTMS Then Active 10 Hz rTMS. Subjects Who Received Sham Followed by Active 10 Hz rTMS Then Active 1 Hz rTMS
Affected / at Risk (%) Affected / at Risk (%)
Total   12/27 (44.44%)   8/31 (25.81%) 
Cardiac disorders     
Increase heart rate  [1]  1/27 (3.70%)  0/31 (0.00%) 
Eye disorders     
eye muscle twitching  [2]  0/27 (0.00%)  2/31 (6.45%) 
General disorders     
Illness  [3]  11/27 (40.74%)  7/31 (22.58%) 
Musculoskeletal and connective tissue disorders     
Jaw pain  [4]  3/27 (11.11%)  1/31 (3.23%) 
Nervous system disorders     
Tinnitus increase  [5]  1/27 (3.70%)  0/31 (0.00%) 
Skin and subcutaneous tissue disorders     
Headache  [6]  4/27 (14.81%)  4/31 (12.90%) 
Indicates events were collected by systematic assessment
[1]
Report of increase heart rate prior to session.
[2]
report of eye muscles twitching after intevention
[3]
reported illness not due to intervention (Flu, orthopedic, back pain, injury)
[4]
In the 1 Hz first arm 3/3 reports of jaw pain were coded as related to the study intervention; whereas in the 10 Hz first arm 0/1 reports were study related.
[5]
In the 1 Hz first arm 1/1 reports of tinnitus increase were coded as related to the study intervention; whereas in the 10 Hz first arm there were no such reports.
[6]
In the 1 Hz first arm 4/4 reports of headache were coded as related to the study intervention; whereas in the 10 Hz first arm 1/4 reports of headache were study related.
Limited recruitment and retention into maintenance (n=3 with complete data) precluded meaningful data analysis.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Mark Mennemeier
Organization: University of Arkansas for Medical Sciences
Phone: 205 410 2413
EMail: msmennemeier@uams.edu
Layout table for additonal information
Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT00926237    
Other Study ID Numbers: 109033
First Submitted: June 19, 2009
First Posted: June 23, 2009
Results First Submitted: October 5, 2020
Results First Posted: November 20, 2020
Last Update Posted: November 20, 2020