Evaluation of the CR Neuromodulation Treatment for Tinnitus (RESET2)

• ClinicalTrials.gov Identifier: NCT01541969
• Recruitment Status: Completed
• First Posted: March 1, 2012
• Results First Posted: June 18, 2015
• Last Update Posted: August 22, 2016
• Sponsor: Nottingham University Hospitals NHS Trust
• Collaborators: University of Nottingham; University College, London
• Information provided by (Responsible Party): Nottingham University Hospitals NHS Trust

Study Description

Brief Summary:

The purpose of this study is to determine whether a new device delivering a sound-based intervention (termed acoustic coordinated reset neuromodulation) has significant clinical benefit for people with intrusive tinnitus. It is hypothesised that the particular pattern of sound stimulation delivered by the device acts to break up patterns of synchronous nerve firing in the brain that may be responsible for the sensation of tinnitus. We will also measure brain activity in a subset of participants to determine if the intervention results in changes in brainwave activity.

Condition or disease	Intervention/treatment	Phase
Tinnitus	Device: CR Neuromodulation; Device: Tinnitus masking	Phase 2; Phase 3

Detailed Description:

Tinnitus affects a large number of people in the UK population but is a poorly understood disorder with no form of treatment that benefits everyone. One theory about tinnitus is that it is caused by altered patterns of synchronous nerve firing in the brains hearing centres. It is believed that conditions such as hearing loss lead to changes in how areas of the brain responsible for hearing are 'wired up' causing large areas of the brain to fire at the same time; this is believed to be a mechanism responsible for the sensation of tinnitus. Research suggests that this type of synchronous activity may be interrupted by presenting very specific sequences of sounds to the ears over several months. If sound stimulation can be used to break up patterns of synchronous activity in the hearing brain, then it is argued that it should also be effective in treating tinnitus. The German company ANM have patented a very specific algorithm of sound simulation that is delivered via headphones from a pocket-sized device. This treatment is currently being marketed by the private healthcare sector in Germany and very recently in the UK. The purpose of this study is to independently test the effects of this new therapy on tinnitus severity and related brain activity. We will gather information using questionnaires and listening tests, and make recording of electrical brain activity using electroencephalography (EEG).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Systematic Evaluation of the Acoustic CR ® Neuromodulation Treatment for Tinnitus
• Study Start Date: August 2012
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: February 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: CR Neuromodulation; Adaptive NeuroModulation (ANM) T30 CR® Neurostimulator device. Participants receive the intervention according to the manufacturer/funder training given to the study team.	Device: CR Neuromodulation; Ear level device which delivers patterned sound stimulation. The experimental arm will use 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. For the first 12 weeks participants will be asked to wear the device every day for 6 hours, and in blocks of time not less than 1 hour. After 12 weeks participants will be unblinded and continue with the same experimental intervention. In weeks 13-36 participants will be asked to wear the device every day for 4 hours, in continuous blocks of at least 1 hour.; Other Name: Acoustic Coordinated Reset Neuromodualtion
Active Comparator: Tinnitus masking; Participants will receive the same Adaptive NeuroModulation (ANM) T30 CR® Neurostimulator device, but it will NOT be programmed according to the therapeutic algorithm (0-12 weeks).	Device: Tinnitus masking; The active comparator uses the same ear level device and also delivers patterned sound but the stimulus will be determined according to an algorithm predicted not to break up tinnitus generating activity in the brain. It may have a masking effect. For the first 12 weeks participants will be asked to wear the device every day for 6 hours, and in blocks of time not less than 1 hour. After 12 weeks, the participants will be unblinded and the device algorithm will be reprogrammed in the same way as the experimental intervention. In weeks 13-24 participants will be asked to wear the device for 6 hours per day, in continuous blocks of at least 1 hour. In weeks 25-36 they will be asked to continue using the device every day for 4 hours, in continuous blocks of at least 1 hour.; Other Name: Tinnitus masking only (by CR Neuromodulation device)

Outcome Measures

Primary Outcome Measures :

1. Tinnitus Handicap Questionnaire (THQ) [ Time Frame: Baseline (visit 2) and 12 weeks (visit 6) ]
   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.

Secondary Outcome Measures :

1. Tinnitus Handicap Inventory (THI) [ Time Frame: Baseline (visit 2) and 12 weeks (visit 6) ]
   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.
2. Tinnitus Functional Index (TFI) [ Time Frame: Baseline (visit 2) and 12 weeks (visit 6) ]
   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.
3. World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) [ Time Frame: Baseline (visit 2) and 12 weeks (visit 6) ]
   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.
4. Percent Change From Baseline in Normalized Oscillatory Power in the Delta Brainwave Pattern as Measured by Electroencephalography (EEG) [ Time Frame: Baseline (visit 2) and 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.

5. Tinnitus Handicap Questionnaire (THQ) [ Time Frame: Baseline (visit 2) and 36 weeks (visit 10) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Pure tone average <60 dB HL in the ear where tinnitus is perceived
• Must be able to hear all stimulation tones presented by the device
• Chronic subjective tinnitus for more than 3 months
• Dominant tinnitus frequency measured between 0.2 and 10 kHz
• At least mild tinnitus score on the Tinnitus Handicap Inventory
• Willing to wear the device for 4-6 hours daily during the trial
• Sufficient command of English language to read, understand and complete the questionnaires
• Able and willing to give informed consent

Exclusion Criteria:

• Objective tinnitus, Meniere's disease, craniomandibular induced Tinnitus
• Pulsatile tinnitus
• Intermittent tinnitus
• Severe anxiety
• Severe depression
• Catastrophic tinnitus
• Hearing-aids wearers for less than 9 months
• Hearing-aid wearers with audiological adjustments within last 3 months
• Absolute thresholds > 70 dB on individual frequencies up to 8 kHz (unable to sufficiently hear the stimulus)
• Taking part in another trial during the last 30 days before study start
• The individually tailored training stimulus is uncomfortable or not acceptable to the participant

Contacts and Locations

Locations

United Kingdom

University College London Ear Institute

London, United Kingdom, WC1X 8EE

NIHR Nottingham Hearing Biomedical Research Unit, University of Nottingham

Nottingham, United Kingdom, NG1 5DU

Sponsors and Collaborators

Nottingham University Hospitals NHS Trust

University of Nottingham

University College, London

Investigators

• Study Director: Deborah A Hall, PhD; NIHR Nottingham Hearing Biomedical Research Unit, Unviersity of Nottingham
• Principal Investigator: Derek J Hoare, PhD; NIHR Nottingham Hearing Biomedical Research Unit, University of Nottingham
• Principal Investigator: David McAlpine, PhD; University College London, Ear Institute

More Information

Additional Information:

Sponsor supported statement about study reporting 

Publications:

Hoare DJ, Edmondson-Jones M, Gander PE, Hall DA. Agreement and reliability of tinnitus loudness matching and pitch likeness rating. PLoS One. 2014 Dec 5;9(12):e114553. doi: 10.1371/journal.pone.0114553. eCollection 2014.

Hoare DJ, Pierzycki RH, Thomas H, McAlpine D, Hall DA. Evaluation of the acoustic coordinated reset (CR®) neuromodulation therapy for tinnitus: study protocol for a double-blind randomized placebo-controlled trial. Trials. 2013 Jul 10;14:207. doi: 10.1186/1745-6215-14-207.

Fackrell K, Hall DA, Barry JG, Hoare DJ. Psychometric properties of the Tinnitus Functional Index (TFI): Assessment in a UK research volunteer population. Hear Res. 2016 May;335:220-235. doi: 10.1016/j.heares.2015.09.009. Epub 2015 Sep 28.

Pierzycki RH, McNamara AJ, Hoare DJ, Hall DA. Whole scalp resting state EEG of oscillatory brain activity shows no parametric relationship with psychoacoustic and psychosocial assessment of tinnitus: A repeated measures study. Hear Res. 2016 Jan;331:101-8. doi: 10.1016/j.heares.2015.11.003. Epub 2015 Nov 14.

Fackrell K, Hall DA, Barry JG, Hoare DJ. Response to Letter: Psychometric properties of the Tinnitus Functional Index (TFI): Assessment in a UK research volunteer population. Hear Res. 2016 May;335:237-238. doi: 10.1016/j.heares.2016.03.014. Epub 2016 Mar 30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hall DA, Pierzycki RH, Thomas H, Greenberg D, Sereda M, Hoare DJ. Systematic Evaluation of the T30 Neurostimulator Treatment for Tinnitus: A Double-Blind Randomised Placebo-Controlled Trial with Open-Label Extension. Brain Sci. 2022 Feb 26;12(3). pii: 317. doi: 10.3390/brainsci12030317.

• Responsible Party: Nottingham University Hospitals NHS Trust
• ClinicalTrials.gov Identifier: NCT01541969
• Other Study ID Numbers: 11IH006
• First Posted: March 1, 2012
• Results First Posted: June 18, 2015
• Last Update Posted: August 22, 2016
• Last Verified: May 2015

Keywords provided by Nottingham University Hospitals NHS Trust:

Ear; Hearing

Additional relevant MeSH terms:

Tinnitus; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases