Serial Audiometry in a Clinical Trial of AIED Treatment

Niparko, John K.; Wang, Nae Yuh; Rauch, Steven D.; Russell, Gregory B.; Espeland, Mark A.; Pierce, June J; Bowditch, Stephen; Masuda, Ann; Gulya, A. Julianna; Gantz, Bruce J.; Hughes, Gordon B.; Brookhouser, Patrick E.; Hannley, Maureen; Telian, Steven A.; Harris, Jeffrey P.

doi:10.1097/01.mao.0000185081.28598.5c

Cited by 55 publications

(52 citation statements)

References 15 publications

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“…Inclusion criteria were described previously 15,16 and were based on the AIED serial audiometry trial inclusion criteria. 17 Patients had SNHL of greater than 30 dB at 1 or more frequencies, with evidence of active decline in at least 1 ear of 15 dB at 1 frequency on their audiogram or 10 dB at 2 or more frequencies developing in more than 3 days but less than 90 days. 17 If the hearing loss evolved in less than 3 days, the patient displayed features suggestive of an autoimmune disorder.…”

Section: Human Subjectsmentioning

confidence: 99%

“…17 Patients had SNHL of greater than 30 dB at 1 or more frequencies, with evidence of active decline in at least 1 ear of 15 dB at 1 frequency on their audiogram or 10 dB at 2 or more frequencies developing in more than 3 days but less than 90 days. 17 If the hearing loss evolved in less than 3 days, the patient displayed features suggestive of an autoimmune disorder. All patients were demonstrated to have no evidence of retrocochlear pathologic conditions, as determined by magnetic resonance imaging.…”

Section: Human Subjectsmentioning

confidence: 99%

“…15,17 Quantitative real-time PCR conditions were as follows: 30 minutes at 48°C (1 cycle), 10 minutes at 95°C (1 cycle…”

Section: Quantitative Real-time Pcr Of Dexamethasone-treated and Untrmentioning

confidence: 99%

See 2 more Smart Citations

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Svrakic¹,

Pathak²,

Goldofsky³

et al. 2012

Arch Otolaryngol Head Neck Surg

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Section: Human Subjectsmentioning

confidence: 99%

Section: Human Subjectsmentioning

confidence: 99%

See 1 more Smart Citation

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Svrakic¹,

Pathak²,

Goldofsky³

et al. 2012

Arch Otolaryngol Head Neck Surg

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“…Finally, even gains in steroid-sensitive AIED patients using corticosteroid therapy may be limited. In the serial audiometry trial for AIED, the average hearing improvement in AIED patients after 1 month of corticosteroid therapy was 4.1 dB for PTA and 7% for WRS (1). During the anakinra trial, the average PTA improvement was 12 dB in anakinra responders compared with 3 dB in nonresponders ( Figure 2A).…”

Section: Discussionmentioning

confidence: 90%

Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease

Vambutas¹,

Lesser²,

Mullooly³

et al. 2014

J. Clin. Invest.

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BACKGROUND. Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals. METHODS.We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (≤10%) and an acceptable (≥30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period. RESULTS.Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84-day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1β plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1β plasma levels. CONCLUSION.We demonstrated that IL-1β inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1β plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1β inhibition is warranted.

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“…Because hearing loss is often suspected to result from immune processes [1], glucocorticoids (prednisone, prednisolone, dexamethasone) are frequently used to treat such hearing disorders as sudden or rapidly progressive hearing loss [2,3,4], Ménière’s disease [5], and autoimmune inner ear disease [6,7]. The glucocorticoids have traditionally been prescribed because of the perceived necessity for their immunosuppressive and anti-inflammatory functions in the ear.…”

Section: Introductionmentioning

confidence: 99%

Blocking the Glucocorticoid Receptor with RU-486 Does Not Prevent Glucocorticoid Control of Autoimmune Mouse Hearing Loss

Trune

Kempton²

2009

Audiol Neurotol

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Background/Aims: Glucocorticoids effectively manage autoimmune hearing loss, although the cochlear mechanisms involved are unknown. Previous studies of steroid-responsive hearing loss in autoimmune (lupus) mice showed glucocorticoids and mineralocorticoids were equally effective, suggesting the ion homeostasis functions of glucocorticoids may be as relevant as immunosuppression for control of autoimmune-induced inner ear disease. Therefore, to better characterize the role of the glucocorticoid receptor in autoimmune hearing loss therapy, its function was blocked with the antagonist RU-486 (mifepristone) during glucocorticoid (prednisolone) treatments. Methods: Following baseline auditory brainstem response (ABR) thresholds, MRL/MpJ-Fas^lpr autoimmune mice were implanted with pellets providing combinations of 1.25 mg/kg of RU-486, 4 mg/kg of prednisolone, or their respective placebos. After 1 month, animals were retested with ABR and blood was collected for immune complex analyses. Results: Mice receiving no prednisolone (placebo + placebo and placebo + RU-486) showed continued declines in hearing. On the other hand, mice receiving prednisolone (prednisolone + placebo and prednisolone + RU-486) had significantly better hearing (p < 0.05) than the non-prednisolone groups. Immune complexes were significantly elevated in the placebo + RU-486 group, suggesting RU-486 effectively blocked glucocorticoid receptor-mediated immune suppression. These results showed that blockage of the glucocorticoid receptor with RU-486 did not prevent prednisolone’s effects in the ear, suggesting its ion homeostasis actions via the mineralocorticoid receptor were more relevant in hearing control. Conclusion: The mineralocorticoid receptor-mediated actions of glucocorticoids are potentially relevant in steroid-responsive hearing disorders, implying disrupted cochlear ion transport functions may underlie the vascular problems proposed in some forms of immune-mediated hearing loss.

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Serial Audiometry in a Clinical Trial of AIED Treatment

Cited by 55 publications

References 15 publications

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease

Blocking the Glucocorticoid Receptor with RU-486 Does Not Prevent Glucocorticoid Control of Autoimmune Mouse Hearing Loss

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