Clinical trial NCT03550430: Neurofeedback for Tinnitus - Does Frequency Specificity Matter?
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tinnitus
Subjective Tinnitus
Chronic Tinnitus
Keywords: tinnitus distress
tinnitus intrusiveness
synchronization by loss of inhibition model (SLIM)
neurofeedback
alpha/delta neurofeedback
beta/theta neurofeedback
electroencephalography (EEG)
tinnitus intensity
tinnitus loudness
Lead sponsor: Philipps University Marburg
Sponsor class: OTHER
Collaborators: name: Eriksholm Research Centre
name: Linkoeping University
name: University Hospital of Gießen and Marburg
First posted: 2018-06-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Tinnitus Handicap Inventory (THI; Newman, Sandridge, & Jacobson, 1998)
timeFrame: 16 weeks
measure: Tinnitus Magnitude Index (TMI; Schmidt, Kerns, Griest, Theodoroff, Pietrzak, & Henry, 2014).
timeFrame: 16 weeks
Secondary outcomes:
measure: Tinnitus Functional Index (TFI; Brüggemann, Szczepek, Kleinjung, Ojo, & Mazurek, 2017)
timeFrame: 16 weeks
measure: Brief Illness Perception Questionnaire (B-IPQ; Broadbent, Petrie, Main, & Weinman, 2006)
timeFrame: 4 weeks
measure: Insomnia Severity Index (ISI; Bastien, Vallières, & Morin, 2001)
timeFrame: 4 weeks
measure: Credibility and Expectancy Questionnaire (CEQ; Devilly & Borkovec, 2000)
timeFrame: 4 weeks
measure: Sustained Attention Response Task (SART; Robertson, Manly, Andrade, Baddeley, & Yiend, 1997)
timeFrame: 16 weeks
measure: Attention Network Test (ANT; Fan, McCandliss, Sommer, Raz, & Posner, 2002)
timeFrame: 16 weeks
measure: Patient Health Questionnaire (PHQ-9; Gräfe, Zipfel, Herzog, & Löwe, 2004)
timeFrame: 16 weeks
Other outcomes:
measure: Satisfaction with treatment
timeFrame: 3 months
Locations:
city: Marburg
country: Germany
facility: Philipps University Marburg, Dept. of Psychology, Division of Clinical Psychology and Psychotherapy
state: Hessen
Study officials:
affiliation: Philipps Universität Marburg
name: Cornelia Weise, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: Gräfe, K., Zipfel, S., Herzog, W., & Löwe, B. (2004). Screening psychischer Störungen mit dem "Gesundheitsfragebogen für Patienten (PHQ-D)". Diagnostica, 50(4), 171-181.
citation: 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.