A Phase 2 interventional study of DMSO-based otic solution with betahistine, dexamethasone, and lidocaine and DMSO-based transdermal cream with levocarnitine and N-acetylcysteine in Tinnitus, sponsored by Leading Edge Clinic. Enrolling by invitation at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-05-13.
Sponsored by Leading Edge Clinic · Phase 2, Interventional, and Treatment
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.
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.
444 studies on the registry are indexed under Tinnitus; 98 are open to participants now.
This study's planned enrollment of 20 is below the median of 60 across 368 interventional studies indexed under Tinnitus.
Browse Tinnitus studies →This is the only study on the registry with Leading Edge Clinic as lead sponsor.
Counted across the registry records on this site, refreshed daily.
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 therapy).
Willing and able to provide .
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 or allergy to dimethyl sulfoxide (DMSO) or any component of the study formulations (betahistine, dexamethasone, lidocaine, levocarnitine, N-acetylcysteine, or ).
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 · Drug: DMSO-based transdermal cream with levocarnitine and N-acetylcysteine
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.
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.
Proportion of participants with at least 50% reduction in Tinnitus Handicap Inventory (THI) score
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.
Time frame: Baseline to Day 30
Change in Tinnitus Handicap Inventory (THI) score over time
Change in total THI score from baseline to Day 30, Month 6, and Month 12. Higher scores indicate greater tinnitus-related handicap.
Time frame: Baseline to Day 30, Month 6, and Month 12
Change in tinnitus loudness on visual analog scale (VAS)
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.
Time frame: Baseline to Day 30, Month 6, and Month 12
Change in tinnitus annoyance/distress on visual analog scale (VAS)
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.
Time frame: Baseline to Day 30, Month 6, and Month 12
Change in sleep interference due to tinnitus on visual analog scale (VAS)
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.
Time frame: Baseline to Day 30, Month 6, and Month 12
Change in concentration difficulty due to tinnitus on visual analog scale (VAS)
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.
Time frame: Baseline to Day 30, Month 6, and Month 12
Patient Global Impression of Change (PGIC) in tinnitus symptoms
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.
Time frame: Day 30, Month 6, and Month 12
Change in concomitant symptom scores (vertigo, insomnia, headache, fatigue) on visual analog scales (VAS)
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.
Time frame: Baseline to Day 30
Incidence of treatment-emergent adverse events
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.
Time frame: From first dose through Day 30
Change in tympanic membrane temperature
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.
Time frame: Baseline to Day 30 (where measured)
Plan to share: No — No individual participant data (IPD) will be shared. Aggregate study results may be published in scientific journals and presented at conferences.
Start is estimated for May 2026; primary completion for Jul 2026, 2 months later.
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