Effect of Aspirin and Folic Acid for Sudden Sensorineural Hearing Loss (SERORL)

Assistance Publique - Hôpitaux de Paris

Status and phase: Begins enrollment in 1 month; Phase 3

Conditions: Sudden Sensorineural Hearing Loss

Treatments: Drug: Aspirin + Acid folic; Drug: Placebo Aspirin + Placebo Acid folic

Study type: Interventional

Funder types: Other

Identifiers

NCT07113158

2024-513710-35 (EudraCT Number)

APHP230836

Details and patient eligibility

About

The annual incidence of sudden sensorineural hearing loss (SSNHL) is 5 to 20 per 100 000 persons. The pathophysiology of SSNHL and acute vestibulo-cochlear syndromes (VCS) is unknown in more than 70% of cases.

Hypothesis : an inner ear microvascular disease represents the key element in the pathogenesis of SSNHL and acute VCS.

Plasma serotonin has among other tissular effect a vasospastic on microcirculation such as the inner ear microvascularisation. Increased plasma homocysteine has a deleterious effect on vascular endothelium. Inner ear microvascularisation sensitized by an increased homocysteine level and the vascular wall would vasoconstrict under serotonin stimulation inducing ischemia of the vestibular and/or cochlear organs.

Full description

Sudden sensorineural hearing loss (SSNHL) is defined as sensorineural hearing loss of 30dB or greater over at least three contiguous audiometric frequencies occurring over 72 hr 9,10. SSNHL is a relatively common disorder in otologic and audiologic practices (1.5-1.7 per 100 new patients presenting in ENT practice. Most patients with sudden SSNHL have no identifiable cause for hearing loss and are classified as "idiopathic". Despite extensive research, the etiology and therapeutic management of SSNHL and acute VCS remain elusive. Regardless of the etiology, complete or partial recovery of hearing thresholds following SSNHL may not occur. Factors influencing hearing recovery include the age at onset of hearing loss, severity and frequencies affected, the presence of vertigo, and the delay of treatment. The incidence of SSNHL is 5-20 per 100, 000. The true incidence of SSNHL may be higher than these estimates because affected individuals who recover spontaneously do not present for medical care. Although individuals of all ages can be affected, the peak incidence is between the fifth and sixth decade of life. Men and women are equally affected. Nearly all cases of SSNHL are unilateral; less than 2% of patients have bilateral involvement and typically bilateral involvement is sequential. Accompanying symptoms include tinnitus (41% to 90%) and dizziness (29% to 56%) New vestibular function assessment now allows us to specify the vestibular damage associated with SSNHL. Until now, the association with dizziness was a poor prognostic factor for hearing. In a recent study in 2023, more than 60% of patients treated for SSNHL had associated vestibular damage even if they did not complain of vestibular symptoms. 20. Vestibular involvement has often been under-diagnosed and could be a way of targeting more precisely the pathophysiological mechanisms behind SSNHL. Vestibular and cochlear damage can be secondary to a pressure disorder of the endolymphatic system (endolymphatic atelectasis or endolymphatic hydrops) or to microvascular damage of cochlear and/or vestibular arteries (e.g. cochlear artery syndrome), but also to inflammatory damage of the labyrinth. 3D-Flair Endolymph magnetic resonance imaging highlighted the different mechanisms involved in deafness: endolymphatic hydrops or atelectasis, microvascular or inflammatory involvement the presence or absence of a rupture of the blood-labyrinth barrier. For all these disorders, increase serum homocysteine and plasma serotonin levels would be a predisposing factor, weakening the microvascularisation inner ear's vascular endothelium.

Enrollment: 142 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Unilateral SSNHL defined as a sudden hearing loss of 30dB or greater at least three contiguous audiometric frequencies (between 125hz and 8000Hz) occurring within a 72 hr period and for less than 15 days.
• Individuals affiliated to a social security regimen
• Individuals able to participate and to follow up during the study period

Exclusion criteria

• Contra-indications to Aspirin, contra-indications to oral corticosteroid therapy, contra-indications to dexamethasone, allergy to vitamin B9
• Evident cause of acute SSNHL including tumor of the ponto-cerebellous angle, infectious labyrinthitis, mechanical and acoustic trauma, malformation of the inner ear, neurological disorder.
• Patient already including in another clinical trial
• Person under legal protection (under guardianship or curatorship)
• Patients taking serotonin reuptake inhibitors
• Patients already taking aspirin or other anticoagulant or antiplatelet agent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

142 participants in 2 patient groups, including a placebo group

Investigational medicinal products

Experimental group

Description:

Aspirin 100 mg/day and Acid Folic 5 mg/day + gold standard treatment (oral corticosteroid therapy 1 mg/kg +/- 3 trans-tympanic injections of dexamethasone) * Corticosteroid therapy 1mg/kg/day for 7 days * 3 trans-tympanic injections of corticosteroids if hearing loss persists at D15 Duration of treatment: 3 months

Treatment:

Drug: Aspirin + Acid folic

Comparator treatment

Placebo Comparator group

Description:

The Placebo Aspirin 100 mg/j + Placebo folic acid 5 mg/j + reference treatment (oral corticosteroid therapy 1mg/kg +/- 3 trans-tympanic injections of dexamethasone) * Corticosteroid therapy 1mg/kg/day for 7 days * 3 trans-tympanic injections of corticosteroids if hearing loss persists at D15 Duration of treatment: 3 months

Treatment:

Drug: Placebo Aspirin + Placebo Acid folic