Trial Outcomes & Findings for Vagus Nerve Stimulation (VNS) Paired With Tones for Tinnitus (NCT NCT01962558)

Results Overview

Assess the number of serious adverse events during the study, and compare between groups to indicate if there are more in the treatment group than the control group.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

30 participants

Primary outcome timeframe

6-weeks

Results posted on

2018-04-06

Participant Flow

Sixty-two subjects were screened for inclusion into the study. Nine (9) did not meet inclusion criteria, 15 declined to participate, 3 had medical issues, and 5 were screened but were after the study limit of 30. Thirty subjects were enrolled and implanted with the study device.

Participant milestones

Participant milestones
Measure	VNS Treatment Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Overall Study STARTED	16	14
Overall Study Acute Study	16	14
Overall Study 12-Weeks	16	14
Overall Study COMPLETED	16	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vagus Nerve Stimulation (VNS) Paired With Tones for Tinnitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VNS Treatment n=16 Participants Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 Participants Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.	Total n=30 Participants Total of all reporting groups
Age, Continuous	55.9 years STANDARD_DEVIATION 7.6 • n=5 Participants	54.9 years STANDARD_DEVIATION 9.1 • n=7 Participants	55.6 years STANDARD_DEVIATION 8.4 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	4 Participants n=7 Participants	19 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	16 participants n=5 Participants	14 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 6-weeks

Assess the number of serious adverse events during the study, and compare between groups to indicate if there are more in the treatment group than the control group.

Outcome measures

Outcome measures
Measure	VNS Treatment n=16 Participants Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 Participants Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Number of Participants With Serious Adverse Events	1 participants	2 participants

SECONDARY outcome

Timeframe: 6-weeks

Assess the number of adverse events during the study, and compare between groups to indicate if there are more in the treatment group than the control group.

Outcome measures

Outcome measures
Measure	VNS Treatment n=16 Participants Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 Participants Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Number of Participants With Adverse Events	11 participants	9 participants

SECONDARY outcome

Timeframe: 6-weeks (pre-implant to after 6-weeks of VNS)

Asses the change in minimum masking level (MML) for both groups and compare between the groups.

Outcome measures

Outcome measures
Measure	VNS Treatment n=16 Participants Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 Participants Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Change in Minimum Masking Level (MML) in Units of dB (Decibels)	3.5 dB (decibels) Interval -0.4 to 7.5	-3.8 dB (decibels) Interval -11.9 to 4.1

SECONDARY outcome

Timeframe: 6-weeks (pre-implant to after 6-weeks of VNS)

Assess the change in THI score for both groups and compare between the groups. The THI is a questionnaire that asks subjects to assess their perception of their tinnitus by rating each question as a Yes (4 points), No (0 points) or Sometimes (2 points). There are 25 questions, scores are summed, so the scale ranges from 0 to 100. Scores are graded as: Grade 1 - Slight (0-16) Only heard in a quiet environment; Grade 2 - Mild (18-36) Easily masked by environmental sounds and easily forgotten with activities.; Grade 3 - Moderate (38-56) Noticed in presence of background noise, although daily activities can still be performed.; Grade 4 - Severe (58-76) Almost always heard, leads to disturbed sleep patterns and can interfere with daily activities.; Grade 5 - Catastrophic (78-100) Always heard, disturbed sleep patterns, difficulty with any activities.

Outcome measures

Outcome measures
Measure	VNS Treatment n=16 Participants Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 Participants Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Percent Change in Tinnitus Handicap Inventory (THI)	-17.7 percentage change of THI Interval -28.0 to -7.3	-7.3 percentage change of THI Interval -27.5 to 12.7

SECONDARY outcome

Timeframe: 6-weeks (pre-implant to after 6-weeks of VNS)

Assess the change in THQ score for both groups and compare between the groups. The THQ is a patient questionnaire with 27 questions with each question having a score from 1 to 100. Scoring includes three factors - Factor 1 (Social, Emotional, Behavioral), Factor 2 (Tinnitus and Hearing), Factor 3 (Outlook). Fifteen questions are included in Factor 1, 8 questions in Factor 2, and 4 questions in Factor 3. A total score is calculated by adding the scores for Factor 1 questions and multiplying by 15/27, adding the scores for Factor 2 and multiplying by 8/27, and adding the scores for Factor 3 and multiplying by 4/27. This is then summed for the total score. Total score ranges from 0 to 100, with higher scores indicating more severe tinnitus.

Outcome measures

Outcome measures
Measure	VNS Treatment n=16 Participants Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 Participants Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Change in Tinnitus Handicap Questionnaire (THQ)	-2.5 units on a scale Interval -8.3 to 3.3	-7.5 units on a scale Interval -15.8 to 0.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 6-weeks (pre-implant to after 6-weeks of VNS)

Assess the change in TFI score for both groups and compare between the groups. The TFI has eight subscales that address the intrusiveness of tinnitus, the sense of control the patient has, cognitive interference, sleep disturbance, auditory issues, relaxation issues, quality of life, and emotional distress. There are a total of 25 questions, with a range of 0 to 10 on each item (0 to 250) total. All valid answers are summed, divided by the number of questions which were answered, and multiplied by 10 (0-100 range). Score range from 0 to 100 with higher scores indicating worse tinnitus.

Outcome measures

Outcome measures
Measure	VNS Treatment n=16 Participants Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 Participants Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Change in Tinnitus Functional Index (TFI)	-2.03 units on a scale Interval -7.1 to 3.1	-7.5 units on a scale Interval -15.5 to 0.7

Adverse Events

VNS Treatment

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

VNS Control

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	VNS Treatment n=16 participants at risk Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 participants at risk Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Respiratory, thoracic and mediastinal disorders Hoarseness	6.2% 1/16 • Number of events 1	7.1% 1/14 • Number of events 1
Surgical and medical procedures Surgery	0.00% 0/16	7.1% 1/14 • Number of events 1

Other adverse events

Other adverse events
Measure	VNS Treatment n=16 participants at risk Vagus nerve stimulation and tones are used 2.5 hours per day for a 6-week period. VNS Treatment: VNS is given in brief bursts over a 2.5 hour period. The subject also has headphone connected to a computer, and hears audio tones through the headphones that occur during VNS.	VNS Control n=14 participants at risk Vagus nerve stimulation and tones are given daily over a 2.5 hour period, but not in the same way as the experimental group, and in such a way that it is believed to be ineffective but still provide both VNS and tones so that blinding is maintained. VNS Control: This is the sham-control group; subjects in this group will receive both tones and VNS, but in a manner that is expected to be ineffective.
Respiratory, thoracic and mediastinal disorders Coughing	12.5% 2/16 • Number of events 2	7.1% 1/14 • Number of events 1

Additional Information

VP Clinical Affairs

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Phone: 512-371-4160

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place