Neurofeedback for Tinnitus - Does Frequency Specificity Matter?

• ClinicalTrials.gov Identifier: NCT03550430
• Recruitment Status: Completed
• First Posted: June 8, 2018
• Last Update Posted: March 10, 2021
• Sponsor: Philipps University Marburg Medical Center
• Collaborators: Eriksholm Research Centre; Linkoeping University; University Hospital of Gießen and Marburg
• Information provided by (Responsible Party): Philipps University Marburg Medical Center

Study Description

Brief Summary:

This study will evaluate the efficacy of an alpha/delta ratio (ADR) neurofeedback training protocol on tinnitus distress. 1/3 of the participants in the study will undergo ADR neurofeedback training, 1/3 an active comparator, beta/theta ratio (BTR) neurofeedback training, whilst the final 1/3 of participants will fill in daily diaries of tinnitus complaints and symptoms for two weeks.

Condition or disease	Intervention/treatment	Phase
Tinnitus; Subjective Tinnitus; Chronic Tinnitus	Behavioral: alpha/delta neurofeedback; Behavioral: beta/theta neurofeedback; Other: Diary completion	Not Applicable

Detailed Description:

Tinnitus is hypothesized to originate as a result of a disturbance in the balance of excitatory and inhibitory neurons in central auditory structures. More specifically, inhibitory neurons hyperpolarize, by which their functional role is weakened . Consequently, this allows auditory neurons, deprived of input from a lesioned auditory system, to spontaneously synchronize their activity, resulting in the tinnitus percept.

In the normal functioning auditory system, neurons firing synchronously in the alpha frequency region (8 - 12 Hz) have a gating function of inhibiting task-irrelevant regions in the brain. In people with chronic tinnitus, it has been observed, that alpha activity over temporal regions is weakened, thus leading to the spontaneous activity characterizing the condition. By upregulating alpha activity with neurofeedback training, it is hypothesized that the excitatory/inhibitory balance in temporal regions can be restored, thus minimizing the tinnitus percept.

The coupling or exchange of information of distinct brain regions, leading to an integrated conscious perception, is assumed to be mediated by delta oscillations. In tinnitus, the distress associated with the condition arises as a consequence of coupling prefrontal areas, responsible for allocation of attentional resources with limbic (arousal) and temporal (auditory processing) regions. In neurofeedback, the downregulation of delta activity is hypothesized to lead to a de-coupling of the communication between the areas associated with the distress.

No studies to date have tested the specific role of alpha and delta in the origin and perpetuation of tinnitus distress and intrusiveness. The present study seeks to compensate for this, by comparing an alpha and delta neurofeedback ratio training protocol with one assumed to have no direct association with the pathophysiology of tinnitus.

In addition to the ten neurofeedback training sessions, all participants undergo diagnostic assessments at three time points throughout the trial (pre-neurofeedback training, post-neurofeedback training and at three months follow-up). For the first 40 participants, electroencephalographic (EEG) activity is recorded and cognitive capacity assessed with two attention tests, the Attention Network Test and Sustained Attention Response Task, respectively at all three time points. For the remaining 80 participants, the EEG recording is abandoned, and only cognitive capacity assessed in the pre- post, and follow-up phase of the study.

EEG recording and attention processes is similarly measured in a control group (n=40) at the pre-neurofeedback training stage. The group is comprised of healthy, age and gender matched participants. Their inclusion serve the purpose of comparing the brain activity, both at rest and during cognitive activity between people with- and people without tinnitus.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study Protocol for a Single-blind Randomized Controlled Trial, Assessing the Specificity of an Alpha/Delta Ratio Neurofeedback Training Protocol in Chronic Tinnitus.
• Actual Study Start Date: October 1, 2018
• Actual Primary Completion Date: August 31, 2020
• Actual Study Completion Date: August 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: ADR neurofeedback; Ten ADR neurofeedback training sessions. The first five sessions comprise four training blocks. The latter five sessions consists of five training blocks each. All training blocks are seven minutes in duration. Participants take between two to three sessions each week.	Behavioral: alpha/delta neurofeedback; neurofeedback training protocol seeking to decrease the alpha/delta ratio, by simultaneous rewarding alpha and inhibiting delta activity.
Active Comparator: BTR neurofeedback; Ten BTR neurofeedback training sessions. The first five sessions comprise four training blocks. The latter five sessions each consists of five training blocks. All training blocks are seven minutes in duration. Participants take between two to three sessions each week.	Behavioral: beta/theta neurofeedback; neurofeedback training protocol seeking to decrease the beta/theta ratio, by simultaneous rewarding beta and inhibiting theta activity.
Active Comparator: Diary Control Group; Daily diary completion for two weeks in the period between baseline and end-point assessments (total period baseline to end-point = four weeks).	Other: Diary completion; completion of diary relating to participants' experience of tinnitus intensity, interference, coping, harm and disability. Rated three times daily on numerical scale (0 - 10) for two weeks.

Outcome Measures

Primary Outcome Measures :

1. Tinnitus Handicap Inventory (THI; Newman, Sandridge, & Jacobson, 1998) [ Time Frame: 16 weeks ]
   Self-report measure of tinnitus handicap assessed pre-intervention, mid-treatment (five sessions), post-intervention and at three month follow-up. The Tinnitus Handicap Inventory is a 25 item questionnaire. Each item is scored 0 - 4 (0 = No, 2 = Sometimes, 4 = Yes), yielding a total between 0 (no handicap) - 100 (catastrophic impact).
2. Tinnitus Magnitude Index (TMI; Schmidt, Kerns, Griest, Theodoroff, Pietrzak, & Henry, 2014). [ Time Frame: 16 weeks ]

   TMI measures tinnitus intensity, three-item scale assessing self-reported severity, loudness and awareness.

   - Visual analogue scale ranges from 0-10 or 0-100, respectively: item 1 (loudness): Range 0 (not at all strong or loud) to 10 (extremely strong or loud) item 2 (awareness): 0 to 100 in increments of 10, with verbal anchors of 0="never aware" and 100="always aware" item 3 (severity): 0-100 with verbal anchors of 0="no tinnitus present" to 100="the worst tinnitus you can imagine"

   • for all items higher values indicate higher tinnitus magnitude
   • values of the three items can be summed up to a total score. For standardisation, items are converted from 0-100 to 0-10.

Secondary Outcome Measures :

1. Tinnitus Functional Index (TFI; Brüggemann, Szczepek, Kleinjung, Ojo, & Mazurek, 2017) [ Time Frame: 16 weeks ]
   The Tinnitus Functional Index (TFI) is a self-report measure of both perceived severity and negative impact of tinnitus. It covers multiple severity domains including but not exclusively quality of sleep, relaxation, sense of control. The TFI questionnaire consists of 25 items, predominantly scored between 0 - 10 bar item 1 and 3, which are expressed as percentages from 0 - 100%.
2. Brief Illness Perception Questionnaire (B-IPQ; Broadbent, Petrie, Main, & Weinman, 2006) [ Time Frame: 4 weeks ]
   The B-IPQ is a nine item self-report measure of individual cognitive and emotional representations of illness. It includes the following domains: consequences of the illness; perception of duration of illness; control over illness; treatment control; symptoms; understanding of illness; emotional response and causes.
3. Insomnia Severity Index (ISI; Bastien, Vallières, & Morin, 2001) [ Time Frame: 4 weeks ]
   A brief scanning measure of insomnia. It consists of 7 items assessing insomnia severity, interference in daily functioning, noticeability of impairment and distress/concern about sleep problems.
4. Credibility and Expectancy Questionnaire (CEQ; Devilly & Borkovec, 2000) [ Time Frame: 4 weeks ]
   a quick and easy-to-administer scale for measuring treatment expectancy and rationale credibility for use in clinical outcome studies
5. Sustained Attention Response Task (SART; Robertson, Manly, Andrade, Baddeley, & Yiend, 1997) [ Time Frame: 16 weeks ]
   measures the ability to sustain attention
6. Attention Network Test (ANT; Fan, McCandliss, Sommer, Raz, & Posner, 2002) [ Time Frame: 16 weeks ]
   assesses orienting, alerting and executive attention processing respectively
7. Patient Health Questionnaire (PHQ-9; Gräfe, Zipfel, Herzog, & Löwe, 2004) [ Time Frame: 16 weeks ]
   Assessment of depressive symptoms

Other Outcome Measures:

1. Satisfaction with treatment [ Time Frame: 3 months ]
   self-developed scale to assess satisfaction with neurofeedback

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:

• Chronic subjective tinnitus, i.e. tinnitus with a duration > 6 months
• At least mild tinnitus distress, corresponding to a score of ≥ 18 on the Tinnitus Handicap Inventory

Exclusion Criteria:

• Moderately severe or severe depression
• Objective tinnitus, where causes are classified according to whether they are vascular or non-vascular in origin
• Current use of psychotropic drugs for a mental health condition
• Bipolar disorder, Attention Deficit Hyperactivity Disorder (ADHD), Psychosis
• Substance abuse
• Current psychotherapeutic treatment for tinnitus, previous biofeedback- or neurofeedback treatment
• A history of seizures, strokes and/or brain hemorrhages

Contacts and Locations

Locations

Germany

Philipps University Marburg, Dept. of Psychology, Division of Clinical Psychology and Psychotherapy

Marburg, Hessen, Germany, 35037

Sponsors and Collaborators

Philipps University Marburg Medical Center

Eriksholm Research Centre

Linkoeping University

University Hospital of Gießen and Marburg

Investigators

• Principal Investigator: Cornelia Weise, Dr.; Philipps Universität Marburg

More Information

Publications:

Balkenhol T, Wallhausser-Franke E, Delb W. Psychoacoustic tinnitus loudness and tinnitus-related distress show different associations with oscillatory brain activity. PLoS One. 2013;8(1):e53180. doi: 10.1371/journal.pone.0053180. Epub 2013 Jan 10.

Dohrmann K, Weisz N, Schlee W, Hartmann T, Elbert T. Neurofeedback for treating tinnitus. Prog Brain Res. 2007;166:473-85. doi: 10.1016/S0079-6123(07)66046-4.

Weisz N, Dohrmann K, Elbert T. The relevance of spontaneous activity for the coding of the tinnitus sensation. Prog Brain Res. 2007;166:61-70. doi: 10.1016/S0079-6123(07)66006-3.

Weisz N, Hartmann T, Muller N, Lorenz I, Obleser J. Alpha rhythms in audition: cognitive and clinical perspectives. Front Psychol. 2011 Apr 26;2:73. doi: 10.3389/fpsyg.2011.00073. eCollection 2011.

Newman CW, Sandridge SA, Jacobson GP. Psychometric adequacy of the Tinnitus Handicap Inventory (THI) for evaluating treatment outcome. J Am Acad Audiol. 1998 Apr;9(2):153-60.

Schmidt CJ, Kerns RD, Griest S, Theodoroff SM, Pietrzak RH, Henry JA. Toward development of a tinnitus magnitude index. Ear Hear. 2014 Jul-Aug;35(4):476-84. doi: 10.1097/AUD.0000000000000017.

Bruggemann P, Szczepek AJ, Kleinjung T, Ojo M, Mazurek B. [Validation of the German Version of Tinnitus Functional Index (TFI)]. Laryngorhinootologie. 2017 Sep;96(9):615-619. doi: 10.1055/s-0042-122342. Epub 2017 May 12. German.

Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 2006 Jun;60(6):631-7. doi: 10.1016/j.jpsychores.2005.10.020.

Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307. doi: 10.1016/s1389-9457(00)00065-4.

Devilly GJ, Borkovec TD. Psychometric properties of the credibility/expectancy questionnaire. J Behav Ther Exp Psychiatry. 2000 Jun;31(2):73-86. doi: 10.1016/s0005-7916(00)00012-4.

Fan J, McCandliss BD, Sommer T, Raz A, Posner MI. Testing the efficiency and independence of attentional networks. J Cogn Neurosci. 2002 Apr 1;14(3):340-7. doi: 10.1162/089892902317361886.

Robertson IH, Manly T, Andrade J, Baddeley BT, Yiend J. 'Oops!': performance correlates of everyday attentional failures in traumatic brain injured and normal subjects. Neuropsychologia. 1997 Jun;35(6):747-58. doi: 10.1016/s0028-3932(97)00015-8.

Gräfe, K., Zipfel, S., Herzog, W., & Löwe, B. (2004). Screening psychischer Störungen mit dem "Gesundheitsfragebogen für Patienten (PHQ-D)". Diagnostica, 50(4), 171-181.

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

Jensen M, Huttenrauch E, Schmidt J, Andersson G, Chavanon ML, Weise C. Neurofeedback for tinnitus: study protocol for a randomised controlled trial assessing the specificity of an alpha/delta neurofeedback training protocol in alleviating both sound perception and psychological distress in a cohort of chronic tinnitus sufferers. Trials. 2020 May 5;21(1):382. doi: 10.1186/s13063-020-04309-y.

• Responsible Party: Philipps University Marburg Medical Center
• ClinicalTrials.gov Identifier: NCT03550430
• Other Study ID Numbers: Neurofeedback for tinnitus
• First Posted: June 8, 2018
• Last Update Posted: March 10, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual participant data for all primary and secondary outcome measures will be made available.
• Supporting Materials: Study Protocol
• Time Frame: Data available within one year of study completion
• Access Criteria: Data access request will be reviewed by the Principal Investigator. Requestors will be required to sign a data access agreement.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Philipps University Marburg Medical Center:

tinnitus distress; tinnitus intrusiveness; synchronization by loss of inhibition model (SLIM); neurofeedback; alpha/delta neurofeedback; beta/theta neurofeedback; electroencephalography (EEG); tinnitus intensity; tinnitus loudness

Additional relevant MeSH terms:

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