Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

An fMRI Investigation of the Effects of IV Lidocaine on Tinnitus

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: NCT04192773
Recruitment Status : Not yet recruiting
First Posted : December 10, 2019
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Dr. Bradley Welling, Massachusetts Eye and Ear Infirmary

Brief Summary:
This is an exploratory pilot open-label study to identify the signal changes on fMRI of patients with tinnitus and with temporary suppression of the tinnitus with IV lidocaine. Patients will include those with hearing loss (both unilateral and bilateral) and tinnitus, subjects with normal hearing and tinnitus, and control subjects with normal hearing and no tinnitus. Eligible subjects will have functional and subjective data collected at baseline, receive an IV lidocaine infusion, and have functional and subjective data collected post-infusion for comparison and identification of involved neural networks.

Condition or disease Intervention/treatment Phase
Tinnitus Drug: IV Lidocaine Early Phase 1

Detailed Description:

A total of 40 subjects will be enrolled in this study. Ten study volunteers will be enrolled in each of the following four groups:

  1. - Normal hearing (NH) without tinnitus (T-)
  2. - Normal hearing (NH) with tinnitus (T+)
  3. - Unilateral hearing loss (uHL) and ipsilateral unilateral tinnitus (uT+)
  4. - Bilateral hearing loss (bHL) and bilateral tinnitus (bT+)

Application of the study treatment may occur at the initial Screening Visit (pending all eligibility requirements can be confirmed) or at Visit 1. The first visit (not including IV lidocaine infusion) should take no more than 3 hours. The investigators will assess patient eligibility and obtain a baseline MRI, audiometry with high frequency, and middle ear muscle reflexes. Three questionnaires (THI, TFI, VAS) will also be given prior to IV lidocaine infusion to assess patients' perception of their tinnitus.

The patient visit and baseline screening may take up to 8 hours total. Patients may have completed the screening/baseline visit on a prior day, in which case the visit should take no more than 5 hours. At the screening/baseline visit, patient will be asked to complete three questionnaires; have an audiogram with high frequency and middle ear reflexes; a pregnancy test if the patient is a woman of childbearing age, and a baseline MRI to assess brain activity. We will also obtain a baseline EKG to evaluate the patient's heart and blood draw to check liver and kidney function. At the infusion visit, patients will receive IV lidocaine infusion for 30 minutes (500mg maximal dose) and an fMRI of the brain. After the infusion, the investigators will draw some blood samples to test for serum lidocaine levels, perform another audiogram with high frequency and middle ear reflexes, and administer the same three questionnaires (THI, TFI, VAS). The investigators will follow-up with patients via email 30 (±7) days after the infusion visit for any adverse event and ask them to complete the three questionnaires (THI, TFI, VAS).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: An fMRI Investigation of the Effects of IV Lidocaine on Tinnitus
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tinnitus

Arm Intervention/treatment
Experimental: IV lidocaine

1000mg/hour IV lidocaine administered for up to 30 minutes (500mg max). Patients will be continuously monitored by a nurse every 5 (±2) minutes to check specifically for vital signs (BP, HR, and RR), patient tinnitus levels, and reports of side effects.

The infusion is continued until any of the following criteria are met: 1) the patient has completed the 30-minute infusion; 2) the patient reports intolerable or concerning side effect, such as dizziness, nausea, or vomiting; 3) the patient experiences bradycardia <50 and a drop of systolic blood pressure (BP) more than 20 mmHg and diastolic pressure more than 10 mmHg during the infusion; 4) the patient reports that tinnitus is resolved, or 5) the patient wishes to stop the study.

Serum lidocaine levels will be drawn by a research nurse upon completion of MRI. The Tinnitus Handicap Inventory, the Tinnitus Functional Index, and the Visual Analog Scale will be administered after IV infusion.

Drug: IV Lidocaine
Using IV lidocaine as intervention and comparing fMRI pre- and post-lidocaine infusion




Primary Outcome Measures :
  1. Compare fMRI scans pre- and post-lidocaine administration to identify neural networks associated with chronic tinnitus. [ Time Frame: 60 MINUTES ]
    The investigators will scan the patient in fMRI prior to IV lidocaine administration. After the infusion, patient will get another fMRI scan to assess any neural changes in the primary auditory cortex and associated salience, limbic and cognitive regions.


Secondary Outcome Measures :
  1. Change in subjective assessment of tinnitus via Tinnitus Handicap Inventory (THI) questionnaire from baseline to post-infusion. [ Time Frame: 30 MINUTES ]
    Patients will be given the questionnaire at baseline to evaluate their tinnitus. The purpose of this questionnaire is to identify difficulties that patients may be experiencing because of their tinnitus. The patients can choose to answer "yes", "sometimes", and "no" to these questions. The higher scores mean worse outcome. The same questionnaire will be given after the infusion to compare questionnaire responses.

  2. Change in subjective assessment of tinnitus via Tinnitus Functional Index (TFI) questionnaire from baseline to post-infusion. [ Time Frame: 30 MINUTES ]
    Patients will be given the questionnaire at baseline to evaluate their tinnitus. Multiple questions probing how the patient's tinnitus has affected different social aspects of their lives are evaluated on the scale of 0 to 10. The higher scores indicate a worse outcome. The same questionnaire will be given after the infusion to compare questionnaire responses.

  3. Change in subjective assessment of tinnitus via Visual Analog Scale (VAS) questionnaire from baseline to post-infusion. [ Time Frame: 30 MINUTES ]
    Patients will be given the questionnaire at baseline to evaluate their tinnitus. The scale evaluates tinnitus loudness, annoyance felt by the patient due to the tinnitus, distress experienced by the patient, and his/her ability to cope with tinnitus. The scale is 10cm long, labeled with 'min' on the left side and 'max' on the right side. Higher scores on the first three categories mean worse outcomes and lower score on the ability to cope means worse outcome. The same questionnaire will be given after the infusion to compare questionnaire responses.

  4. Compare blood oxygen level (O2) dependent signal derived from pre- and post-infusion fMRI. [ Time Frame: 30 MINUTES ]
    The investigators will compare measured blood O2 level dependent activity on fMRI images pre- and post-infusion.



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

-Age ≥ 18

  • Ability to provide informed consent
  • English speaker
  • Falls under one of the four groups a. Normal Hearing without Tinnitus (NH/T-) i. Normal Hearing as defined as pure tone thresholds of 25 dB or less across all tested frequencies ii. Subjective confirmation of lack of tinnitus* 1. Never or rarely b. Normal Hearing with Tinnitus (NH/T+) i. Normal Hearing Normal Hearing as defined as pure tone thresholds of 25 dB or less across all tested frequencies ii. Subjective confirmation of tinnitus* 1. Often, always c. Unilateral hearing loss and ipsilateral unilateral tinnitus (uHL/uT+) i. Unilateral hearing loss as defined by pure tone thresholds of 50 dB or greater across 3 frequencies in the bad ear and 25 dB or less in good ear ii. Subjective confirmation of tinnitus in the good ear* 1. Often, always d. Bilateral hearing loss and bilateral tinnitus (bHL/bT+) i. Bilateral hearing loss as defined by pure tone thresholds of 50 dB or greater across 3 frequencies in both ears ii. Subjective confirmation of tinnitus in both ears*

    1. Often, always

      • Tinnitus will be confirmed via Likert-scale: Never - Rarely - Sometimes - Often - Always

Exclusion Criteria:

  • Currently undergoing tinnitus treatment with other pharmacologic agents

    a. Patients may be eligible if they complete a 60 day washout period from pharmacologic agents treating tinnitus

  • Inability to tolerate fMRI or other contraindications of fMRI including claustrophobia or presence of ferromagnetic objects in the body that cannot be removed.
  • Contraindications to IV lidocaine administration such known allergy to lidocaine
  • History of myocardial infarction or cardiac arrhythmias including Wolff-Parkinson-White, severe sinoatrial, atrioventricular or intraventricular heart block in the absence of a pacemaker
  • History of seizure disorder
  • Resting BP of <100/50
  • Currently taking antiarrhythmics
  • Have taken antibiotics within 48 hours of infusion
  • Known hepatic failure
  • Pregnant or lactating women
  • Patient with other neurological or psychiatric disorders, such as stroke, brain tumor, schizophrenia, bipolar disorder.
  • Patients who cannot fill out the questionnaires

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): NCT04192773


Contacts
Layout table for location contacts
Contact: Simonyan Lab 617-573-6016 simonyan_lab@meei.harvard.edu
Contact: Amy Quinkert, PhD 617-573-4192 amy_quinkert@meei.harvard.edu

Sponsors and Collaborators
Massachusetts Eye and Ear Infirmary
Investigators
Layout table for investigator information
Principal Investigator: Brad Welling, MD, PhD Massachusetts Eye and Ear
Layout table for additonal information
Responsible Party: Dr. Bradley Welling, Chief of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT04192773    
Other Study ID Numbers: 2019P000
First Posted: December 10, 2019    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: May 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Bradley Welling, Massachusetts Eye and Ear Infirmary:
tinnitus
normal control
hearing loss
IV lidocaine
fMRI
Additional relevant MeSH terms:
Layout table for MeSH terms
Tinnitus
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Lidocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action