Trial Outcomes & Findings for Evaluation of the CR Neuromodulation Treatment for Tinnitus (NCT NCT01541969)
NCT ID: NCT01541969
Last Updated: 2016-08-22
Results Overview
Change in the global score on a 27 item, multi-attribute questionnaire measure of the functional impact of tinnitus (0-100 scale). Change was computed as 'visit 2' - 'visit 6' and so a positive change score indicates a reduction of tinnitus symptoms.
COMPLETED
PHASE2/PHASE3
100 participants
Baseline (visit 2) and 12 weeks (visit 6)
2016-08-22
Participant Flow
First patient first visit, 28 May 2012 Last patient last visit, 26 February 2014
217 screen fails: Ménière(6), neuroma(2), TMJ(3), hearing loss(2), new hearing-aid user(11), recent hearing-aid adjustments(2), severe anxiety(4), severe depression(5), pulsatile TI(7), somatic TI(17), intermittent TI(7), slight TI(35), catastrophic TI(6), pitch match not possible(7), pitch out of fitting range(56), prescription tones inaudible(47)
Participant milestones
| Measure |
CR Neuromodulation
Acoustic Co-ordinated Reset (CR) Neuromodulation includes an ear level device which delivers patterned sound stimulation. Participants were asked to wear the device for 4-6 hours per day (0-12 weeks) and for at least 4 hours daily (12-36 weeks)
The experimental arm received the intervention in a double-blind RCT (0-12 weeks), with the device fitted according to audiologist training given by the manufacturer/funder. An individually specified sound stimulation algorithm is hypothesised to interrupt tinnitus generating activity in the brain.
After the first 12 weeks, the participants entered into the open-label extension (unblinded, 12-36 weeks) in which they continued with the same experimental intervention.
|
Tinnitus Masking
The active control group had the same ear level device which delivers patterned sound stimulation. Participants were asked to wear the device for 4-6 hours per day (0-36 weeks).
The active comparator group received the intervention in a double-blind RCT (0-12 weeks). They received the same device as the treatment group but the sound stimulation was determined according to an algorithm predicted not to break up tinnitus generating activity in the brain. The device may have a tinnitus masking effect in the active comparator group.
After the first 12 weeks, the participants entered into the open-label extension (unblinded, 12-36 weeks) in which they received the verum experimental intervention.
|
|---|---|---|
|
Double-blind (0-12 Weeks)
STARTED
|
50
|
50
|
|
Double-blind (0-12 Weeks)
COMPLETED
|
44
|
48
|
|
Double-blind (0-12 Weeks)
NOT COMPLETED
|
6
|
2
|
|
Open Label Extension (12-36 Weeks)
STARTED
|
44
|
48
|
|
Open Label Extension (12-36 Weeks)
COMPLETED
|
33
|
35
|
|
Open Label Extension (12-36 Weeks)
NOT COMPLETED
|
11
|
13
|
Reasons for withdrawal
| Measure |
CR Neuromodulation
Acoustic Co-ordinated Reset (CR) Neuromodulation includes an ear level device which delivers patterned sound stimulation. Participants were asked to wear the device for 4-6 hours per day (0-12 weeks) and for at least 4 hours daily (12-36 weeks)
The experimental arm received the intervention in a double-blind RCT (0-12 weeks), with the device fitted according to audiologist training given by the manufacturer/funder. An individually specified sound stimulation algorithm is hypothesised to interrupt tinnitus generating activity in the brain.
After the first 12 weeks, the participants entered into the open-label extension (unblinded, 12-36 weeks) in which they continued with the same experimental intervention.
|
Tinnitus Masking
The active control group had the same ear level device which delivers patterned sound stimulation. Participants were asked to wear the device for 4-6 hours per day (0-36 weeks).
The active comparator group received the intervention in a double-blind RCT (0-12 weeks). They received the same device as the treatment group but the sound stimulation was determined according to an algorithm predicted not to break up tinnitus generating activity in the brain. The device may have a tinnitus masking effect in the active comparator group.
After the first 12 weeks, the participants entered into the open-label extension (unblinded, 12-36 weeks) in which they received the verum experimental intervention.
|
|---|---|---|
|
Double-blind (0-12 Weeks)
Dominant pitch match not possible
|
0
|
1
|
|
Double-blind (0-12 Weeks)
Pitch shifted out of fitting range
|
1
|
1
|
|
Double-blind (0-12 Weeks)
Withdrawal by Subject
|
2
|
0
|
|
Double-blind (0-12 Weeks)
Lost to Follow-up
|
1
|
0
|
|
Double-blind (0-12 Weeks)
Adverse Event
|
2
|
0
|
|
Open Label Extension (12-36 Weeks)
Pitch shifted out of fitting range
|
1
|
1
|
|
Open Label Extension (12-36 Weeks)
Prescription adjusted: tones inaudible
|
1
|
0
|
|
Open Label Extension (12-36 Weeks)
Withdrawal by Subject
|
1
|
1
|
|
Open Label Extension (12-36 Weeks)
Lost to Follow-up
|
6
|
8
|
|
Open Label Extension (12-36 Weeks)
Adverse Event
|
2
|
3
|
Baseline Characteristics
Evaluation of the CR Neuromodulation Treatment for Tinnitus
Baseline characteristics by cohort
| Measure |
CR Neuromodulation
n=50 Participants
see Protocol section for details
|
Tinnitus Masking
n=50 Participants
see Protocol section for details
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.1 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
51.8 years
STANDARD_DEVIATION 12.2 • n=7 Participants
|
50.5 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Hearing level (better ear)
|
13.1 decibel hearing level (dB HL)
STANDARD_DEVIATION 10.2 • n=5 Participants
|
14.3 decibel hearing level (dB HL)
STANDARD_DEVIATION 12.0 • n=7 Participants
|
13.7 decibel hearing level (dB HL)
STANDARD_DEVIATION 11.2 • n=5 Participants
|
|
Hearing level (worse ear)
|
18.5 decibel hearing level (dB HL)
STANDARD_DEVIATION 12.4 • n=5 Participants
|
18.7 decibel hearing level (dB HL)
STANDARD_DEVIATION 12.4 • n=7 Participants
|
18.6 decibel hearing level (dB HL)
STANDARD_DEVIATION 12.3 • n=5 Participants
|
|
Tinnitus Handicap Inventory
|
40.0 units on a scale
STANDARD_DEVIATION 17.4 • n=5 Participants
|
40.9 units on a scale
STANDARD_DEVIATION 15.8 • n=7 Participants
|
40.2 units on a scale
STANDARD_DEVIATION 16.4 • n=5 Participants
|
|
Beck Anxiety Inventory
|
4.7 units on a scale
STANDARD_DEVIATION 4.7 • n=5 Participants
|
5.4 units on a scale
STANDARD_DEVIATION 6.6 • n=7 Participants
|
5.1 units on a scale
STANDARD_DEVIATION 5.7 • n=5 Participants
|
|
Beck Depression Inventory
|
8.7 units on a scale
STANDARD_DEVIATION 6.4 • n=5 Participants
|
9.0 units on a scale
STANDARD_DEVIATION 7.3 • n=7 Participants
|
8.7 units on a scale
STANDARD_DEVIATION 6.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (visit 2) and 12 weeks (visit 6)Population: We have analyzed both complete case and multiple imputed data for the mean change in global THQ score from baseline (visit 2) to 12 weeks (visit 6). Here we report complete case data.
Change in the global score on a 27 item, multi-attribute questionnaire measure of the functional impact of tinnitus (0-100 scale). Change was computed as 'visit 2' - 'visit 6' and so a positive change score indicates a reduction of tinnitus symptoms.
Outcome measures
| Measure |
CR Neuromodulation
n=42 Participants
see Protocol section for details
|
Tinnitus Masking
n=44 Participants
see Protocol section for details
|
|---|---|---|
|
Tinnitus Handicap Questionnaire (THQ)
|
3.75 units on a scale
Standard Deviation 13.29
|
4.02 units on a scale
Standard Deviation 9.56
|
SECONDARY outcome
Timeframe: Baseline (visit 2) and 12 weeks (visit 6)Population: We have analyzed both complete case and multiple imputed data for the mean change in global THI score from baseline (visit 2) to 12 weeks (visit 6). Here we report complete case data.
Change in the global score on a 25 item, multi-attribute questionnaire measure of the functional impact of tinnitus (0-100 scale). Change was computed as 'visit 2' - 'visit 6' and so a positive change score indicates a reduction of tinnitus symptoms.
Outcome measures
| Measure |
CR Neuromodulation
n=43 Participants
see Protocol section for details
|
Tinnitus Masking
n=45 Participants
see Protocol section for details
|
|---|---|---|
|
Tinnitus Handicap Inventory (THI)
|
2.84 units on a scale
Standard Deviation 14.89
|
1.64 units on a scale
Standard Deviation 10.81
|
SECONDARY outcome
Timeframe: Baseline (visit 2) and 12 weeks (visit 6)Population: We have analyzed both complete case and multiple imputed data for the mean change in global TFI score from baseline (visit 2) to 12 weeks (visit 6). Here we report complete case data.
Change in the global score on a 25 item, multi-attribute questionnaire measure of the functional impact of tinnitus (0-100 scale). Change was computed as 'visit 2' - 'visit 6' and so a positive change score indicates a reduction of tinnitus symptoms.
Outcome measures
| Measure |
CR Neuromodulation
n=43 Participants
see Protocol section for details
|
Tinnitus Masking
n=45 Participants
see Protocol section for details
|
|---|---|---|
|
Tinnitus Functional Index (TFI)
|
2.38 units on a scale
Standard Deviation 19.70
|
4.45 units on a scale
Standard Deviation 14.85
|
SECONDARY outcome
Timeframe: Baseline (visit 2) and 12 weeks (visit 6)Population: We have analyzed both complete case and multiple imputed data for the mean change in Q1 score from baseline (visit 2) to 12 weeks (visit 6). Here we report complete case data.
The WHOQOL-BREF is a 26-item, multi-attribute questionnaire measure of health related quality of life. Outcome was measured as a change on Question 1: 'How would you rate your quality of life (over the past 4 weeks)?' There are 5 response options (Very poor=1; Poor=2; Neither poor nor good=3; Good=4; Very good=5). Change was computed as 'visit 2' - 'visit 6' and so a positive change score indicates a reduction in self-perceived quality of life.
Outcome measures
| Measure |
CR Neuromodulation
n=43 Participants
see Protocol section for details
|
Tinnitus Masking
n=45 Participants
see Protocol section for details
|
|---|---|---|
|
World Health Organization Quality of Life Questionnaire (WHOQOL-BREF)
|
-0.21 units on a scale
Standard Deviation 0.64
|
-0.11 units on a scale
Standard Deviation 0.61
|
SECONDARY outcome
Timeframe: Baseline (visit 2) and 12 weeks (visit 6)Population: The EEG assessment was offered only to the first 50 participants enrolled at the Nottingham site. We have analyzed only complete case data for the mean change in delta band power from baseline (visit 2) to 12 weeks (visit 6).
Non-invasive recording to measure rhythmic patterns of spontaneous brain activity at rest. An a priori hypothesis targeted normalized delta rhythm. Band powers were calculated as percent change in delta brainwave pattern relative to change in total (1-90 Hz) EEG band. Comparison made between 'visit 2' and 'visit 6'. We used a Neuroscan system (SynAmps2 model 8050, Compumedics Neuroscan, Charlotte, NC, USA) and custom cap with 66 equidistant scalp electrodes (Easycap, GmbH, Germany). A central frontal electrode was used as ground and a nose-tip electrode as reference. Electrode impedances were maintained at 5 kΩ prior to recordings. Recording was done with an offline filter of 0.5 to 200 Hz pass-band and 1 kHz sampling rate. Recording was over a continuous 10-minute period. Participants were seated in a quiet, darkened soundproof booth and were instructed to relax, keep eyes open and fix gaze on a marker point.
Outcome measures
| Measure |
CR Neuromodulation
n=20 Participants
see Protocol section for details
|
Tinnitus Masking
n=22 Participants
see Protocol section for details
|
|---|---|---|
|
Percent Change From Baseline in Normalized Oscillatory Power in the Delta Brainwave Pattern as Measured by Electroencephalography (EEG)
|
0.001 Percent change
Standard Deviation 0.01
|
0.004 Percent change
Standard Deviation 0.013
|
SECONDARY outcome
Timeframe: Baseline (visit 2) and 36 weeks (visit 10)Population: We have analyzed both complete case and multiple imputed data for the mean change in global THQ score from baseline (visit 2) to 36 weeks (visit 10). Here we report complete case data.
Change in the global score on a 27 item, multi-attribute questionnaire measure of the functional impact of tinnitus (0-100 scale). Change was computed as 'visit 2' - 'visit 10' and so a positive change score indicates a reduction of tinnitus symptoms.
Outcome measures
| Measure |
CR Neuromodulation
n=30 Participants
see Protocol section for details
|
Tinnitus Masking
n=33 Participants
see Protocol section for details
|
|---|---|---|
|
Tinnitus Handicap Questionnaire (THQ)
|
5.41 units on a scale
Standard Deviation 15.64
|
6.01 units on a scale
Standard Deviation 10.52
|
Adverse Events
Acoustic CR Neuromodulation
Tinnitus Masking
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Acoustic CR Neuromodulation
n=50 participants at risk
see Protocol section for details
|
Tinnitus Masking
n=50 participants at risk
see Protocol section for details
|
|---|---|---|
|
Ear and labyrinth disorders
Tinnitus worsened
|
8.0%
4/50 • Number of events 4 • Adverse events data were collected across the 36 weeks.
The definition of an adverse event in the context of this study is: (1) since wearing the ear-level device tinnitus intrusiveness increased and made the condition unbearable, (2) a disease or symptoms (unrelated to tinnitus) that was present at baseline and wosened following the start of the study.
|
6.0%
3/50 • Number of events 3 • Adverse events data were collected across the 36 weeks.
The definition of an adverse event in the context of this study is: (1) since wearing the ear-level device tinnitus intrusiveness increased and made the condition unbearable, (2) a disease or symptoms (unrelated to tinnitus) that was present at baseline and wosened following the start of the study.
|
Additional Information
Professor Deborah Hall, Professor of Hearing Sciences
University of Nottingham
Results disclosure agreements
- Principal investigator is a sponsor employee The manufacturer acknowledges and accepts the right of the investigator to publish the results of the research, however, the Investigator shall send a draft manuscript of the publication or abstract of the study findings to the manufacturer 30 days in advance of submission to a scientific journal for approval. Adaptive Neuromodulation GmbH was the manufacturer at the start of the trial, subsequently passing to NeuroTherapies Reset (Brook Henderson Group) during open-label extension.
- Publication restrictions are in place
Restriction type: OTHER