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

NCT07567274 | Enrolling By Invitation Phase 2

• 1 other identifier: IMIRB-202600105
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tinnitus

Keywords

Chronic subjective tinnitus; Refractory tinnitus; Tinnitus; Long COVID; Post-acute sequelae of SARS-CoV-2 (PASC); Post-COVID-19 vaccine injury; COVID-19 vaccine-associated tinnitus; Dimethyl sulfoxide; DMSO; DMSO dual-route therapy; Otic DMSO; Transdermal DMSO; Compounded otic drops; Compounded transdermal cream; Tinnitus Handicap Inventory; THI; Telemedicine clinical trial; Indigenous medicine; Botanical medicine

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Day 30

Secondary Outcomes (9)

• Change in Tinnitus Handicap Inventory (THI) score over time

  Baseline to Day 30, Month 6, and Month 12

• Change in tinnitus loudness on visual analog scale (VAS)

  Baseline to Day 30, Month 6, and Month 12

• Change in tinnitus annoyance/distress on visual analog scale (VAS)

  Baseline to Day 30, Month 6, and Month 12

• Change in sleep interference due to tinnitus on visual analog scale (VAS)

  Baseline to Day 30, Month 6, and Month 12

• Change in concentration difficulty due to tinnitus on visual analog scale (VAS)

  Baseline to Day 30, Month 6, and Month 12

Study Arms (1)

DMSO Dual-Route Therapy

EXPERIMENTAL

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

Interventions

DMSO-based otic solution with betahistine, dexamethasone, and lidocaine DRUG

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.

DMSO Dual-Route Therapy

DMSO-based transdermal cream with levocarnitine and N-acetylcysteine DRUG

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.

DMSO Dual-Route Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Leading Edge Clinic: lead
• Rebuild Medicine Inc: collaborator

Study Sites (1)

Nationwide Telemedicine Study (Leading Edge Clinic)

Ithaca, New York, 14851, United States

Location

Related Publications (2)

• Newman CW, Jacobson GP, Spitzer JB. Development of the Tinnitus Handicap Inventory. Arch Otolaryngol Head Neck Surg. 1996 Feb;122(2):143-8. doi: 10.1001/archotol.1996.01890140029007.

  PMID: 8630207 BACKGROUND

• Caro AZ. Dimethyl sulfoxide therapy in subjective tinnitus of unknown origin. Ann N Y Acad Sci. 1975 Jan 27;243:468-74. doi: 10.1111/j.1749-6632.1975.tb25389.x.

  PMID: 1055561 BACKGROUND

MeSH Terms

Conditions

Tinnitus; Post-Acute COVID-19 Syndrome

Interventions

Betahistine; Dexamethasone; Lidocaine; Carnitine; Acetylcysteine

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Scott D Marsland, MS Nursing

  Leading Edge Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intervention Model: Single Group Assignment. This is a prospective, single-arm trial in which all enrolled participants receive the same DMSO-based dual-route therapy (otic liquid plus transdermal cream) for 30 days, with no control or comparison group.

Study Record Dates

• First Submitted: May 1, 2026
• First Posted: May 5, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)