Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Investigating Disinhibitory Brain Mechanism in Tinnitus and Hearing Loss (IGNITE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04862572
Recruitment Status : Not yet recruiting
First Posted : April 28, 2021
Last Update Posted : April 28, 2021
Sponsor:
Collaborator:
Nottingham University Hospitals NHS Trust
Information provided by (Responsible Party):
University of Nottingham

Brief Summary:

Tinnitus, the perception of sound in the absence of an external acoustic stimulus. Tinnitus is often perceived inside the head rather than the ear and is a common condition with a prevalence estimated between 10 and 15% in adults. Between 1 and 3% of this population are having a significant impact on their quality of life. Despite its high prevalence, the underlying mechanisms of tinnitus still remain unclear.

The majority of tinnitus cases associated with some degree of hearing loss, making hearing loss the biggest risk factor for tinnitus. Recently, it has been suggested that hearing deficits, such as speech-in-noise difficulty, can exist in the absence of any overt hearing loss within the audiometric range (0.125-8 kHz). This is referred to as "hidden hearing loss" and has been suggested to be associated with hearing loss at above-audiometric (> 8 kHz) frequencies.

This project is aimed at studying the underlying mechanisms of tinnitus and the possible relation with overt or hidden hearing loss. Specifically, the investigators want to test the hypothesis that tinnitus is caused by maladaptive plasticity arising as a result of auditory input deprivation. This idea is supported by the finding that tinnitus may disappear when the hearing, and thus auditory input, recover. Disruptions at lower levels of the auditory pathway could lead to alterations in synaptic transmission and neurotransmitter release in more central regions of the auditory system (e.g., in the auditory cortex). This may create an imbalance between neuronal excitation and inhibition, and re-routing of auditory pathways, leading to abnormal neural excitability and connectivity.

In this study, the investigators question whether auditory cortex disinhibition is specifically related to tinnitus, or is a consequence of hearing loss. To answer this question, the investigators propose to conduct a study that aims to investigate the inhibition mechanism by quantifying GABA concentration level, neural activity and functional connectivity strength of auditory cortex using non-invasive imaging techniques, namely Magnetic Resonance Spectroscopy (MRS) and functional Magnetic Resonance Imaging (fMRI). The investigators expected to possibly provide a tinnitus biomarker, and this may help to direct future treatments.


Condition or disease Intervention/treatment Phase
Tinnitus Hearing Loss Other: MRI scanning Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Cross sectional case-control multimodal MRI, audio- and psychometric study
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Investigating Disinhibitory Brain Mechanism in Tinnitus and Hearing Loss: Is There a Maladaptive Signature of Auditory Cortex GABA Loss and Dysconnectivity?
Estimated Study Start Date : April 2021
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: People with tinnitus
People with tinnitus will undergo all interventions (audiology test, MRI scans, tinnitus-related questionnaires).
Other: MRI scanning

In the audiological assessment, participants will undergo various audiometric test, such as pure tone audiometry with extended high-frequency range, speech audiometry, tympanometry, and auditory reflex threshold. These tests are all noninvasive and aim to assess participants hearing threshold, speech-in-noise difficulty, whether or not they have conductive hearing loss, and test efferent auditory function. The appointment will take around 60-90 minutes. An experienced audiologist on-site will be in charge of this procedure.

In the MRI appointment, participant will undergo MRI scanning. Before the MRI scan, a researcher with experienced radiographer will re-check that the participant is safe to be scanned, with the standard University of Nottingham safety questionnaire. This rechecking step is necessary to make sure that participants are still eligible for the scanning. An experience radiographer will be in charge of this procedure.

Other Name: Audiological assessment

Experimental: People without tinnitus
People with tinnitus will undergo most of all interventions (audiology test, MRI scans) except filling up the tinnitus-related questionnaires.
Other: MRI scanning

In the audiological assessment, participants will undergo various audiometric test, such as pure tone audiometry with extended high-frequency range, speech audiometry, tympanometry, and auditory reflex threshold. These tests are all noninvasive and aim to assess participants hearing threshold, speech-in-noise difficulty, whether or not they have conductive hearing loss, and test efferent auditory function. The appointment will take around 60-90 minutes. An experienced audiologist on-site will be in charge of this procedure.

In the MRI appointment, participant will undergo MRI scanning. Before the MRI scan, a researcher with experienced radiographer will re-check that the participant is safe to be scanned, with the standard University of Nottingham safety questionnaire. This rechecking step is necessary to make sure that participants are still eligible for the scanning. An experience radiographer will be in charge of this procedure.

Other Name: Audiological assessment




Primary Outcome Measures :
  1. GABA neurotransmitter level measured using MRS and neural activity and connectivity strength in auditory resting-state networks using functional MRI scan. [ Time Frame: During 3-6 months after the data has been collected ]

    Primary test:

    • Univariate group comparison between-group differences in imaging outcomes: auditory cortex GABA, local functional connectivity density (REHO), interhemispheric auditory cortices functional connectivity, cross-modal functional connectivity between auditory and visual cortex, auditory cortex neural activity (using BOLD response) to visual attention task.
    • Between-group test for differences in correlation: GABA and hearing loss, auditory cortex functional connectivity and hearing loss.


Secondary Outcome Measures :
  1. Measures of GABA level in the auditory cortex and correlation with tinnitus severity scores and tinnitus negative affect scores. [ Time Frame: During 3-6 months after the data has been collected ]

    Secondary test:

    • Within-group correlation analysis of GABA level with audiometric results indexing sensory deafferentation.
    • Regression analysis of GABA level with tinnitus severity.

  2. Measures of neural activity, and connectivity changes in brain-wide and correlation of these measures with tinnitus severity scores and tinnitus negative affect scores. [ Time Frame: During 3-6 months after the data has been collected ]

    Secondary test:

    • Within-group correlation analysis of functional connectivity and neural activity to attention) with audiometric results indexing sensory deafferentation.
    • Regression analysis of functional connectivity and neural activity with tinnitus severity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Are age 18-80 years.
  • Are eligible to be scanned using MRI and to undergo audiometry and psychometry.
  • Are able to give informed consent.
  • Must have a good comprehension of English in order to complete the hearing-related questionnaires

Exclusion Criteria:

  • Pregnant women will be excluded based on MRI safety recommendations.
  • Past medical history of acoustic neuroma and Ménière's disease.
  • Significant past medical history that may affect brain GABA and functional metrics such as stroke, multiple sclerosis, epilepsy, diabetes, cardiovascular, major neurodegenerative or psychiatric conditions, cancer requiring systemic chemotherapy or brain radiotherapy.
  • Individuals who had in last 3 months and/or currently taking a sedating or GABA enhancing or psychoactive drugs (opioids, anti-depressants).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04862572


Contacts
Layout table for location contacts
Contact: Anissa Ramadhani +44 (0)115 748 4389 anissa.ramadhani@nottingham.ac.uk
Contact: Katrin Krumbholz, Dr. +44 (0)115 748 6941 katrin.krumbholz@nottingham.ac.uk

Sponsors and Collaborators
University of Nottingham
Nottingham University Hospitals NHS Trust
Investigators
Layout table for investigator information
Study Director: Dorothee Auer, Prof. University of Nottingham
Principal Investigator: Anissa Ramadhani University of Nottingham
Additional Information:
Publications:
Hoffman, H. J., & Reed, G. W. (2004). Epidemiology of tinnitus. Tinnitus: Theory and management, 16, 16-41.

Layout table for additonal information
Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT04862572    
Other Study ID Numbers: 21020
First Posted: April 28, 2021    Key Record Dates
Last Update Posted: April 28, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: In accordance with the University of Nottingham's, the Government's, and our funders' policies the research data may be shared with researchers in other universities and organizations, including those in other countries, for research in health and social care. Data sharing in this way is usually anonymized. Although the detail of what and how to share them will need to be followed up.
Supporting Materials: Analytic Code
Time Frame: Data will become available 3 months after the last data acquisition. They will be available up to 3 years.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Nottingham:
Tinnitus
Hearing loss
Inhibition
Functional connectivity
Structural connectivity
Additional relevant MeSH terms:
Layout table for MeSH terms
Hearing Loss
Deafness
Tinnitus
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases