DMSO Dual-Route Therapy for Refractory Tinnitus in Long-COVID and Post-COVID-19 Vaccine Injury (DART-TINN)

May 8, 2026 updated by: Leading Edge Clinic

Single-Arm Pilot Study of Compounded DMSO-Based Dual-Route Therapy for Refractory Subjective Tinnitus in PASC and Post-COVID-19 Vaccine Injury

The goal of this clinical trial is to test a compounded dimethyl sulfoxide (DMSO)-based dual-route therapy for adults with refractory subjective tinnitus linked to long-COVID (post-acute sequelae of SARS-CoV-2) or post-COVID-19 vaccine injury. Participants have bothersome tinnitus that has not improved with at least two prior standard treatments.

All participants will receive two study treatments for 30 days: a DMSO-based ear canal liquid and a DMSO-based transdermal cream applied to the skin around the ears and upper neck. The ear drops are used every 4 days, and the cream is applied once daily at bedtime. Both formulations are prepared by a licensed compounding pharmacy.

The main question is whether at least half of the participants achieve a 50% or greater reduction in their Tinnitus Handicap Inventory (THI) score from baseline to Day 30. Researchers will also look at changes in tinnitus loudness and annoyance, sleep and concentration, other symptoms such as vertigo, insomnia, headache, and fatigue, and any side effects.

After an initial in-person ear, nose, and throat (ENT) evaluation, all study visits are conducted by telemedicine. Participants complete electronic questionnaires through a secure, HIPAA-compliant system over 12 months of follow-up.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Subjective non-pulsatile tinnitus is a common and often debilitating symptom in patients with post-acute sequelae of SARS-CoV-2 (PASC, long-COVID) and post-COVID-19 vaccine injury. Mechanisms are thought to include neuroinflammation, microvascular dysfunction, oxidative stress, and mitochondrial impairment within cochlear and central auditory pathways. A substantial proportion of patients remain highly symptomatic despite standard therapies such as sound therapy, cognitive behavioral approaches, antidepressants, and corticosteroids. No FDA-approved curative pharmacologic therapy exists for chronic subjective tinnitus.

Dimethyl sulfoxide (DMSO) is a tree-derived solvent with anti-inflammatory, antioxidant, vasodilatory, and penetration-enhancing properties. A foundational open-label study in the 1970s reported that DMSO-based formulations combined with vasoactive and anti-inflammatory agents improved or resolved subjective tinnitus in most treated patients, but this approach has not been systematically evaluated in modern refractory PASC or vaccine-injury cohorts. This pilot trial modernizes that historical concept using current compounding standards and telemedicine-enabled follow-up.

This is a prospective, single-arm, open-label pilot study of approximately 20 adults with refractory subjective tinnitus attributed to PASC or post-COVID-19 vaccine injury. All participants receive a dual-route regimen for 30 days: (1) a DMSO-based otic liquid instilled into the external auditory canal every 4 days, and (2) a DMSO-based transdermal cream applied once daily to the bilateral mastoid regions, periauricular skin, and upper posterior neck. Both formulations are compounded by a licensed pharmacy according to protocol specifications. Standard tinnitus counseling and sound therapy are allowed, but no new tinnitus-specific medications may be started during the 30-day treatment window.

The primary objective is to estimate the proportion of participants achieving at least a 50% reduction in Tinnitus Handicap Inventory (THI) score from baseline to Day 30. Secondary objectives include changes in THI score at later time points, visual analog scale (VAS) ratings of tinnitus loudness, annoyance, sleep interference, and concentration, patient global impression of change, and VAS measures of concomitant symptoms such as vertigo, insomnia, headache, and fatigue. Safety and tolerability are assessed by monitoring adverse events, including expected DMSO-related effects such as transient odor or skin irritation. Exploratory measures may include changes in tympanic membrane temperature and audiometric parameters where available.

Screening and informed consent are performed via telemedicine, followed by a required baseline in-person ENT evaluation with otoscopy, audiometry, and completion of the THI and other questionnaires. During the 30-day treatment period, participants have regular telemedicine check-ins and complete electronic questionnaires through a secure, HIPAA-compliant REDCap-based platform. Follow-up assessments occur at approximately 6 and 12 months to evaluate durability of tinnitus response and longer-term safety. As a pilot study, analyses are descriptive and use paired pre- and post-treatment comparisons to generate effect-size estimates and feasibility data for future controlled trials.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Ithaca, New York, United States, 14851
        • Nationwide Telemedicine Study (Leading Edge Clinic)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Inclusion Criteria:

Adults 18 to 70 years of age.

Chronic subjective non-pulsatile tinnitus for at least 6 months.

Bothersome tinnitus defined by a Tinnitus Handicap Inventory (THI) score ≥ 20 at screening.

Documented history of post-acute sequelae of SARS-CoV-2 (PASC, long COVID) or post-COVID-19 vaccine injury, with tinnitus onset or clear worsening temporally associated with that event.

Failure of at least two prior tinnitus therapies (for example, sound therapy, counseling or cognitive-behavioral approaches, pharmacologic treatments, or steroid therapy).

Willing and able to provide informed consent.

Able to complete telemedicine visits and electronic questionnaires in English and to attend a baseline in-person otolaryngology (ENT) evaluation.

Exclusion Criteria:

Objective or pulsatile tinnitus, or tinnitus primarily synchronous with the heartbeat.

Active middle-ear infection, acute otitis media, tympanic membrane perforation, or current otorrhea.

Recent exposure (within the past 3 months) to known ototoxic medications associated with new or rapidly worsening tinnitus.

Known hypersensitivity or allergy to dimethyl sulfoxide (DMSO) or any component of the study formulations (betahistine, dexamethasone, lidocaine, levocarnitine, N-acetylcysteine, or excipients).

Pregnancy or breastfeeding.

Uncontrolled or severe psychiatric illness (for example, active psychosis, acute suicidality) that, in the opinion of the investigator, would interfere with participation or completion of questionnaires.

Inability to comply with study procedures, including telemedicine visits, electronic data capture, or topical/otic dosing instructions.

Any other otologic or neurologic condition judged by the investigator to confound tinnitus assessment or pose unacceptable risk with DMSO-based therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DMSO Dual-Route Therapy
All participants receive compounded DMSO-based dual-route therapy consisting of a DMSO-based otic liquid applied to the external auditory canal every 4 days and a DMSO-based transdermal cream applied once daily to the mastoid and periauricular regions and upper posterior neck for 30 days.
Drug: DMSO-based otic solution with betahistine, dexamethasone, and lidocaine
Compounded otic liquid containing dimethyl sulfoxide (DMSO) 50% (v/v), betahistine dihydrochloride 8 mg/mL, dexamethasone sodium phosphate 0.2 mg/mL, and lidocaine hydrochloride 1%. Instill 2 mL into the external auditory canal of the affected ear(s) every 4 days (total of 8 applications over 30 days). Formulation is prepared by a licensed compounding pharmacy according to protocol specifications.
Drug: DMSO-based transdermal cream with levocarnitine and N-acetylcysteine
Compounded transdermal cream containing dimethyl sulfoxide (DMSO) 60% (w/w), levocarnitine 10% (w/w), and N-acetylcysteine 10% (w/w). Apply approximately 1.5 mL (pea- to quarter-sized amount) once daily at bedtime to the bilateral mastoid regions, periauricular skin, and upper posterior neck, with occlusion for 60 minutes or overnight, then wash off in the morning. Formulation is prepared by a licensed compounding pharmacy according to protocol specifications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants with at least 50% reduction in Tinnitus Handicap Inventory (THI) score
Time Frame: Baseline to Day 30
The Tinnitus Handicap Inventory (THI) is a 25-item validated questionnaire (total score 0-100) that measures tinnitus-related handicap. Responders are defined as participants with a reduction of at least 50% in total THI score from baseline to Day 30.
Baseline to Day 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Tinnitus Handicap Inventory (THI) score over time
Time Frame: Baseline to Day 30, Month 6, and Month 12
Change in total THI score from baseline to Day 30, Month 6, and Month 12. Higher scores indicate greater tinnitus-related handicap.
Baseline to Day 30, Month 6, and Month 12
Change in tinnitus loudness on visual analog scale (VAS)
Time Frame: Baseline to Day 30, Month 6, and Month 12
Participants rate tinnitus loudness on a 0-10 visual analog scale (0 = no tinnitus, 10 = worst imaginable). Change is calculated as follow-up minus baseline at each time point.
Baseline to Day 30, Month 6, and Month 12
Change in tinnitus annoyance/distress on visual analog scale (VAS)
Time Frame: Baseline to Day 30, Month 6, and Month 12
Participants rate how annoying or distressing their tinnitus is on a 0-10 visual analog scale (0 = not at all annoying, 10 = extremely annoying). Change is calculated as follow-up minus baseline.
Baseline to Day 30, Month 6, and Month 12
Change in sleep interference due to tinnitus on visual analog scale (VAS)
Time Frame: Baseline to Day 30, Month 6, and Month 12
Participants rate how much tinnitus interferes with sleep on a 0-10 visual analog scale (0 = no interference, 10 = extreme interference). Change is calculated as follow-up minus baseline.
Baseline to Day 30, Month 6, and Month 12
Change in concentration difficulty due to tinnitus on visual analog scale (VAS)
Time Frame: Baseline to Day 30, Month 6, and Month 12
Participants rate how much tinnitus interferes with concentration on a 0-10 visual analog scale (0 = no interference, 10 = extreme interference). Change is calculated as follow-up minus baseline.
Baseline to Day 30, Month 6, and Month 12
Patient Global Impression of Change (PGIC) in tinnitus symptoms
Time Frame: Day 30, Month 6, and Month 12
Participants rate overall change in their tinnitus on a 7-point Patient Global Impression of Change scale (1 = very much improved, 7 = very much worse). Outcomes will be summarized as the proportion reporting "much improved" or "very much improved" and as distribution across all categories.
Day 30, Month 6, and Month 12
Change in concomitant symptom scores (vertigo, insomnia, headache, fatigue) on visual analog scales (VAS)
Time Frame: Baseline to Day 30
Participants rate vertigo, insomnia, headache, and fatigue on separate 0-10 visual analog scales (0 = no symptom, 10 = worst imaginable). Change in each symptom score from baseline to Day 30 will be summarized descriptively.
Baseline to Day 30
Incidence of treatment-emergent adverse events
Time Frame: From first dose through Day 30
Number and proportion of participants experiencing treatment-emergent adverse events, including expected DMSO-related effects (e.g., garlic-like odor, transient warmth or flushing, skin irritation) and any serious or unexpected events. Events will be coded and summarized by severity and relationship to study treatment.
From first dose through Day 30
Change in tympanic membrane temperature
Time Frame: Baseline to Day 30 (where measured)
In participants with local ENT follow-up, tympanic membrane temperature is measured at baseline and Day 30. Change in temperature will be summarized descriptively as an exploratory biomarker of local vascular and inflammatory effects.
Baseline to Day 30 (where measured)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leading Edge Clinic

Collaborators

Rebuild Medicine Inc

Investigators

  • Principal Investigator: Scott D Marsland, MS Nursing, Leading Edge Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 15, 2026

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

May 1, 2026

First Submitted That Met QC Criteria

May 1, 2026

First Posted (Actual)

May 5, 2026

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMIRB-202600105

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No individual participant data (IPD) will be shared. Aggregate study results may be published in scientific journals and presented at conferences.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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