Clinical trial NCT04934371: Treatment of Tinnitus With Noninvasive Neuromodulation and Listening Therapy
Official title: Treatment of Tinnitus With Noninvasive Neuromodulation and Listening Therapy: A Double-blind, Sham-controlled, Crossover Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Tinnitus, Subjective
Hyperacusis
Hearing Disorders
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2021-06-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each patient will undergo tDCS and active listening therapy. This will be double-blinded randomized-sham controlled intervention during which excitatory/anodal tDCS or sham will be administered alongside active listening therapy 5 times a week for 2 weeks. After 2-month follow up participants will be crossed-over to the other treatment type. (Model AB- BA
Primary purpose: TREATMENT

Brief summary: The goal of this study is to use non-invasive transcranial direct current stimulation (tDCS) combined with active listening therapy to treat tinnitus and hyperacusis and related conditions.

Detailed description: Tinnitus is characterized by the subjective perception of sound in the ears or in the brain without external stimulus. In about 30-50% of patients, tinnitus co-occurs with hyperacusis, which is abnormal sensitivity to sounds even at low levels. Chronic tinnitus and hyperacusis can be devastating since a significant proportion of sufferers develop sleep disturbances, psychiatric conditions, and a small fraction commit suicide. Tinnitus is often accompanied by difficulty concentrating and impairment on tasks that require sustained attention and executive control. Currently there is no satisfactory treatment for tinnitus and hyperacusis, contributing to patients' distress. Thus, there is an urgent need for interventions that would suppress the symptoms and possibly cure the disorder. Although, the pathophysiology of tinnitus and hyperacusis is not well understood, neurobiological research suggests that tinnitus and hyperacusis can be attributed to maladaptive neuroplasticity triggered by damage in the auditory system. Most symptoms of tinnitus have been attributed to the hyperactivity and reorganization in the auditory cortex (AC) and dorsolateral prefrontal brain regions (DLPFC). This suggests that electrical stimulation to the abnormally activated regions might modulate these overactive regions and reduce tinnitus and hyperacusis. TDCS is a noninvasive neurostimulation technique that uses weak electric currents (1-2 mA) applied to the scalp to modulate brain responsiveness by temporarily altering neuronal resting membrane potentials. It is proposed that this approach has a potential therapeutic value in treating tinnitus and hyperacusis.

Our proposed project examines whether application of tDCS to AC and DLPFC combined with active listening therapy serves to promote adaptive neuroplasticity and reduce subjective perception of sound and emotional distress.

The Aims are to: (1) Determine whether tDCS can lead to significant improvement in tinnitus and hyperacusis symptoms pre- versus post-stimulation and

(2) Examine electrophysiological responses and functional connectivity in the fronto-temporal-parietal network of brain regions in response to tDCS vs. sham.

The expected outcomes from this research will provide evidence to support the design and implementation of individualized tDCS protocols to potentiate treatment protocols that address the core deficits in tinnitus and hyperacusis. Our data will contribute to a more detailed understanding of the neurobiology of tinnitus and the mechanisms that contribute to the subjective, emotional and cognitive symptoms. The results of our study have a potential to develop effective treatment for the rehabilitation of tinnitus and contribute to the clinical practice.

Summary of study sequence and procedures:

Week 1: Baseline screening, hearing assessment, tinnitus assessment (2 hours), one magnetic resonance imaging (MRI) scan (45minutes), one electrophysiology recording (EEG-ERP)( 1 hour) Weeks 2-4: tDCS with active listening therapy Part 1

* 2 weeks of 1-hour sessions using non-invasive brain stimulation paired with active listening therapy

Weeks 5 and 6: rest-period, post-treatment assessment, one MRI scan (45 min), one EEG-ERP session (1hour)

Weeks 7 to 9: tDCS with active listening therapy Part 2 (1 hour each sessions)

* 2 weeks of 1-hour sessions using non-invasive brain stimulation paired with active listening therapy

Weeks 10 and 12: rest period and post-treatment assessment one MRI scan (45 min), one EEG-ERP session (1hour)

Week 18: 2-month follow-up, tinnitus assessment, one MRI scan (45 min), one EEG-ERP session (1 hour)

Eligibility criteria: Inclusion Criteria:

* chronic tinnitus and or hyperacusis (\> 8 months)
* adults (18-80 years old)

Exclusion Criteria:

* implanted metal or devices including cochlear implants,
* bullet wounds, head/neck tattoo,
* metal in the eyes,
* other diagnosed neurological disorders (e.g., stroke, Parkinson's, dementia, brain tumors),
* head trauma or brain surgery, psychiatric disorders,
* personal or family history of epilepsy, other seizure disorders
* Individuals with a history of Meniere's Disease, pulsatile tinnitus, otosclerosis, and
* chronic headaches.
* conductive hearing loss, or
* fluctuating hearing thresholds
* pure tone averages \>70dB HL

Primary outcomes:
measure: Mean change in tinnitus severity and annoyance on the tinnitus hearing survey (THS)
timeFrame: through study completion, an average of 1 year
measure: Mean change in the Sound Tolerance Questionnaire ratings
timeFrame: through study completion, an average of 1 year
measure: mean change on the Tinnitus Functional Index (TFI) scores
timeFrame: through study completion, an average of 1 year
measure: mean change on the Tinnitus Primary Function Questionnaire (TPFQ)
timeFrame: through study completion, an average of 1 year
measure: Mean change in tinnitus and hyperacusis ratings on the Visual Analog Scale
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: change in electrophysiological measures
timeFrame: through study completion, an average of 1 year
measure: change in functional connectivity measured with fMRI
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
Study officials:
affiliation: University of Arizona
name: Aneta Kielar, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arul-Anandam AP, Loo C, Sachdev P. Transcranial direct current stimulation - what is the evidence for its efficacy and safety? F1000 Med Rep. 2009 Jul 27;1:58. doi: 10.3410/M1-58.
citation: Baguley DM. Hyperacusis. J R Soc Med. 2003 Dec;96(12):582-5. doi: 10.1177/014107680309601203. No abstract available.
citation: Cardon E, Joossen I, Vermeersch H, Jacquemin L, Mertens G, Vanderveken OM, Topsakal V, Van de Heyning P, Van Rompaey V, Gilles A. Systematic review and meta-analysis of late auditory evoked potentials as a candidate biomarker in the assessment of tinnitus. PLoS One. 2020 Dec 17;15(12):e0243785. doi: 10.1371/journal.pone.0243785. eCollection 2020.
citation: Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006 Apr;117(4):845-50. doi: 10.1016/j.clinph.2005.12.003. Epub 2006 Jan 19.
citation: Henry JA, Griest S, Zaugg TL, Thielman E, Kaelin C, Galvez G, Carlson KF. Tinnitus and hearing survey: a screening tool to differentiate bothersome tinnitus from hearing difficulties. Am J Audiol. 2015 Mar;24(1):66-77. doi: 10.1044/2014_AJA-14-0042.