Oral Statins for Hearing Loss

Overseen By Donna Whitlon, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Northwestern University

Must be taking: Oral steroids

Must not be taking: Ototoxic medications, Statins, Antidepressants, others

Disqualifiers: Diabetes, Heart disease, Psychiatric syndromes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

A small clinical trial for idiopathic sudden sensorineural hearing loss (ISSNHL). Will the addition of an oral statin to the standard treatment (oral methylprednesolone and the salvage therapy of intratympanic dexamethasone) improve the treatment outcome for patients with ISSNHL? This study will compare the two treatments and quantitatively evaluate hearing and speech discrimination and have the patients subjectively evaluate tinnitus.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used statins in the last 12 months or have had oral steroid treatment in the last 30 days. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug for hearing loss?

Research shows that dexamethasone, when administered directly into the ear, can help prevent the worsening of hearing loss in conditions like Ménière's disease, with some patients even experiencing improvement. This suggests that steroids like dexamethasone may have potential in treating hearing loss. ^{1 2 3 4 5}

How is the drug used in the Oral Statins for Hearing Loss trial different from other treatments for hearing loss?

The treatment in the trial uses oral steroids like dexamethasone and methylprednisolone, which are typically used for their anti-inflammatory effects, and this approach is unique because it explores the potential of these drugs to protect hearing by reducing inflammation, unlike traditional treatments that may not focus on inflammation control. ^{1 4 6 7 8}

Research Team

Donna Whitlon, Ph.D.

Principal Investigator

Northwestern University

Eligibility Criteria

Adults aged 18-80 with sudden one-sided hearing loss, diagnosed within the first two weeks of symptoms. Participants must have a significant level of hearing loss and be fluent in English. Excluded are those with prior similar events, certain diseases (like diabetes or severe neurological conditions), history of substance abuse, recent steroid use, ear anomalies, or who've taken statins or ototoxic drugs recently.

Inclusion Criteria

Your average hearing loss is 30 decibels or more across three specific frequencies.

I speak and understand English very well.

Seen in the clinic within the first 14 days after the onset of symptoms

Exclusion Criteria

You are allergic or sensitive to any parts of the study medication.

I have taken statins in the past year.

I have a genetic condition that affects my hearing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive oral methylprednisolone and either a statin or placebo for 7 days, with potential intratympanic dexamethasone if no improvement after 2 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including hearing tests and tinnitus evaluation

up to 4 months

2 visits (in-person)

Treatment Details

Interventions

• dexamethasone
• methylprednisolone
• Placebo
• Statin

Trial Overview The trial is testing if adding an oral statin to standard treatment for sudden sensorineural hearing loss improves outcomes. Standard treatment includes methylprednisolone and intratympanic dexamethasone as salvage therapy. Hearing improvement and tinnitus will be measured.

Participant Groups

Group I: Statin Experimental Treatment 3 Interventions

Methylprednisolone+statin (identity and dose to be determined before Trial Begins) Oral methyprednisolone, tapering dose over 11 days, beginning at 16 mg 4 x a day; Oral statin 1 dose per day for 7 days, beginning with the first dose of methylprednisolone: If no improvement after two weeks, offer up to 2 doses intratympanic dexamethasone (10 mg/cc) 10 days apart.

Group II: Placebo Placebo Group 3 Interventions

Methylprednisolone+ placebo. Oral methyprednisolone, tapering dose over 11 days, beginning at 16 mg 4 x a day; Oral placebo 1 dose per day for 7 days, beginning with the first dose of methylprednisolone If no improvement after two weeks, offer up to 2 doses intratympanic dexamethasone (10 mg/cc) 10 days apart.

dexamethasone is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Decadron for:

• Allergic reactions
• Blood diseases
• Eye diseases
• Skin diseases
• Respiratory diseases
• Rheumatic diseases
• Gastrointestinal diseases

Approved in European Union as Dexamethasone for:

• Cerebral edema
• Acute asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic reactions
• Skin diseases
• Eye diseases

Approved in Canada as Dexamethasone for:

• Allergic reactions
• Blood diseases
• Eye diseases
• Skin diseases
• Respiratory diseases
• Rheumatic diseases

Approved in Japan as Dexamethasone for:

• Cerebral edema
• Acute asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic reactions
• Skin diseases
• Eye diseases

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

In a 12-month study of 17 patients with refractory autoimmune hearing loss, low-dose methotrexate (MTX) was found to be well tolerated and led to hearing improvement in 65% of participants.

MTX also showed positive effects on vertigo symptoms, with 5 out of 9 patients with Meniere's disease experiencing improvement, suggesting it may be a beneficial treatment for autoimmune-related hearing issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open trial of methotrexate as treatment for autoimmune hearing loss. Matteson, EL., Fabry, DA., Facer, GW., et al.[2022]

A 68-year-old male patient with inner ear inflammation and chronic sinusitis experienced significant improvement in hearing loss and sinus symptoms after switching from oral steroids to topical betamethasone, highlighting a potential alternative treatment for those with adverse reactions to systemic steroids.

Audiometry results showed a notable recovery in hearing, with improvements from 50 dB to 20 dB in the right ear and from 70 dB to 35 dB in the left ear, suggesting that topical steroid therapy can effectively address inner ear conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical ocular drug delivery to inner ear disease and sinusitis. Mimura, T., Funatsu, H., Usui, T., et al.[2014]

In a study of 67 patients with idiopathic sensorineural hearing loss, pulse therapy with intravenous methylprednisolone did not show a significant advantage over traditional oral prednisolone in improving hearing outcomes.

Both treatment methods resulted in similar levels of hearing improvement, indicating that pulse therapy may not be more effective than standard oral prednisolone for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulse steroid therapy in idiopathic sudden sensorineural hearing loss: A randomized controlled clinical trial. Eftekharian, A., Amizadeh, M.[2022]

Polymer-eluted dexamethasone (DXM) effectively protects hair cells from TNFalpha-induced loss by altering gene expression, promoting cell survival in an in vitro model using organ of Corti explants.

The study demonstrated that while the polymer alone did not provide protection, the combination of the polymer with DXM significantly reduced hair cell loss, suggesting potential for use in cochlear implants to preserve hearing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biopolymer-released dexamethasone prevents tumor necrosis factor alpha-induced loss of auditory hair cells in vitro: implications toward the development of a drug-eluting cochlear implant electrode array. Dinh, C., Hoang, K., Haake, S., et al.[2013]

In a study of 105 patients with Ménière's disease, intratympanic dexamethasone treatment resulted in hearing stagnation in 68.6% of cases, indicating its effectiveness in preventing further hearing loss.

Additionally, 12.4% of patients experienced actual hearing improvement after treatment, demonstrating a significant correlation between dexamethasone administration and positive auditory outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratympanically administered steroid for progressive sensorineural hearing loss in Ménière's disease. Molnár, A., Maihoub, S., Tamás, L., et al.[2020]

Systemic administration of dexamethasone before cochlear implantation significantly enhances the distribution of the steroid in the inner ear, particularly in areas critical for hearing, such as the organ of Corti and stria vascularis.

The findings support the use of systemic steroids during cochlear implant surgeries to improve hearing preservation, as they show increased uptake in the cochlea despite local administration typically yielding higher drug levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochlear implant surgery facilitates intracochlear distribution of perioperative systemic steroids. Creber, NJ., Eastwood, HT., Hampson, AJ., et al.[2023]

In a study of 35 adult patients undergoing cochlear implantation, those receiving intravenous dexamethasone showed a high rate of partial hearing preservation (77.8%), indicating its effectiveness in maintaining residual hearing post-surgery.

The combination of intravenous dexamethasone and oral prednisone also resulted in significant hearing preservation (61.5%), while the control group without steroid treatment had a higher incidence of no measurable hearing (38.5%) after 12 months, highlighting the potential benefits of steroid therapy in cochlear implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Effect of Steroid Therapy on Preserving Residual Hearing after Cochlear Implantation with the Advanced Bionics HiRes Ultra 3D Cochlear Implant System. Skarzynska, MB., Kolodziejak, A., Gos, E., et al.[2022]

Dexamethasone (Dex) effectively inhibits the activity of the diastrophic dysplasia sulfate transporter (DTDST) in otosclerotic stapes, suggesting a potential mechanism for reducing bone turnover in otosclerosis.

The inhibition of DTDST by Dex is linked to a decrease in interleukin-6 (IL-6) secretion specifically in otosclerotic cells, indicating that glucocorticoids may help manage inflammation and bone remodeling in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucocorticoids inhibit diastrophic dysplasia sulfate transporter activity in otosclerosis by interleukin-6. Imauchi, Y., Lombès, M., Lainé, P., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Open trial of methotrexate as treatment for autoimmune hearing loss. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Topical ocular drug delivery to inner ear disease and sinusitis. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

Pulse steroid therapy in idiopathic sudden sensorineural hearing loss: A randomized controlled clinical trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Biopolymer-released dexamethasone prevents tumor necrosis factor alpha-induced loss of auditory hair cells in vitro: implications toward the development of a drug-eluting cochlear implant electrode array. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Intratympanically administered steroid for progressive sensorineural hearing loss in Ménière's disease. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Cochlear implant surgery facilitates intracochlear distribution of perioperative systemic steroids. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The Clinical Effect of Steroid Therapy on Preserving Residual Hearing after Cochlear Implantation with the Advanced Bionics HiRes Ultra 3D Cochlear Implant System. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Glucocorticoids inhibit diastrophic dysplasia sulfate transporter activity in otosclerosis by interleukin-6. [2018]