Therapeutic Efficacy of Tiludronic Acid on Inner Ear Involvement in Advanced Otosclerosis (OTOPHOS)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Therapeutic Efficacy of Tiludronic Acid on Inner Ear Involvement in Advanced Otosclerosis|
- Hearing preservation on pure-tone audiometry at 2 years [ Time Frame: year 2 ] [ Designated as safety issue: No ]
Effect on hearing preservation as assessed by air conduction pure-tone average at 2 years.
Hearing deterioration is defined by a deterioration of pure-tone average by air conduction >20 dB at 500, 1000, 2000 and 4000 Hz between inclusion and the end of the observation period.
- hearing preservation at one year [ Time Frame: year 1 ] [ Designated as safety issue: No ]Effect on hearing preservation as assessed by air conduction pure-tone average at 1 year
- cochlear function [ Time Frame: years 1 and 2 ] [ Designated as safety issue: No ]Effect on cochlear function preservation as evaluated by bone conduction pure-tone average (500, 1000, 2000 and 4000 Hz) at 1 and 2 years.
- Stapedial reflex preservation [ Time Frame: years 1 and 2 ] [ Designated as safety issue: No ]Percentage of stapedial reflex preservation on the controlateral ear if unilateral otosclerosis at 1 and 2 years.
- Speech reception threshold and speech discrimination score [ Time Frame: years 1 and 2 ] [ Designated as safety issue: No ]Effect on speech reception threshold ans speech discrimination score at 1 and 2 years.
- Tinnitus and balance disorders [ Time Frame: years 1 and 2 ] [ Designated as safety issue: No ]Effect on the prevalence and the intensity of tinnitus and balance disorders as evaluated by questionnary at 1 and 2 years.
- Radiological bone density [ Time Frame: year 2 ] [ Designated as safety issue: No ]Effect on radiological bone density at fissula ante fenestram as assessed on high resolution temporal bone CT-scans before and after treatment by calculation of fissula ante fenestram / temporal bone squama cortex bone density ration on axial views.
- Tolerance [ Time Frame: month 3 ] [ Designated as safety issue: Yes ]Clinical tolerance during treatment
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||January 2017|
|Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Drug: tiludronic acid
400 mg / day for 3 months
Placebo Comparator: Control
400 mg / day for 3 month
Otosclerosis is a bone dystrophy localized to middle and inner ears with unknown etiology. It principally concerns adult patients between 30 and 50 years of age. Women present with this disease 2 times more frequently than men. Family cases are observed in 50% with a dominant autosomal transmission and low penetrance (40%). In its early stages, the disease is mainly located at the stapediovestibular joint leading to its ankylosis and a conductive hearing loss. In its advanced stages, the lesions extend around the cochlea and vestibule, induce a sensorineural hearing loss which can progress to severe and profound deafness, and prolonged balance disorders. On CT-scan, disease foci show a demineralization. Their density is inversely correlated to the hearing loss. In early stage, hearing function is currently rehabilitated by conventional hearing aids or surgery. In advanced forms, cochlear involvement is not accessible to surgery, and rehabilitation is insured by he hearing aids or cochlear implants. Vestibular dysfunction is dealt with by physiotherapy or symptomatic treatment. Drugs with anabolic activity in bone, such as sodium fluoride and etidronate (first generation bisphosphonate, Didronel ®), appear to reduce the hearing loss and to increase the radiological density of disease foci. However, their efficacy is low and poorly documented. Their effect on vestibular function is unknown.
Moreover, ototoxicity has been reported for etidronate. New biphosphonates such as tiludronic acid (Skelid ®) have a significantly more potent inhibition of bone resorption and do not have an ototoxic effect. They have been used for the treatment or the prevention of postmenopausal osteoporosis and in Paget's disease with mild to moderate adverse effects in the majority of cases.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01617057
|Paris, France, 92118|
|Principal Investigator:||Alexis BOZORG-GRAYELI, Pr||Hôpital Général, CHU de Dijon|