The goal of this clinical trial is to test a compounded dimethyl sulfoxide (DMSO)-baseddual-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 havebothersome 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 canalliquid and a DMSO-based transdermal cream applied to the skin around the ears and upperneck. The ear drops are used every 4 days, and the cream is applied once daily atbedtime. Both formulations are prepared by a licensed compounding pharmacy.The main question is whether at least half of the participants achieve a 50% or greaterreduction in their Tinnitus Handicap Inventory (THI) score from baseline to Day 30.Researchers will also look at changes in tinnitus loudness and annoyance, sleep andconcentration, other symptoms such as vertigo, insomnia, headache, and fatigue, and anyside effects.After an initial in-person ear, nose, and throat (ENT) evaluation, all study visits areconducted by telemedicine. Participants complete electronic questionnaires through asecure, 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.
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.
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.
Nationwide Telemedicine Study (Leading Edge Clinic)
Ithaca, New York, United States
Scott D Marsland, MS Nursing, Principal Investigator
Leading Edge Clinic