Therapeutic Efficacy of Tiludronic Acid on Inner Ear Involvement in Advanced Otosclerosis (OTOPHOS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01617057
First received: June 8, 2012
Last updated: March 12, 2014
Last verified: March 2014
  Purpose

The aim of this study is to assess the efficacy of a biphosphonate (tiludronic acid, Skelid®, Sanofi-Aventis) in the treatment of inner ear involvement in advanced otosclerosis


Condition Intervention Phase
Otosclerosis
Drug: tiludronic acid
Drug: Placebo
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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


Enrollment: 31
Study Start Date: May 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Skelid
tiludronic acid
Drug: tiludronic acid
400 mg / day for 3 months
Other Name: tiludronic acid
Placebo Comparator: Control
Placebo
Drug: Placebo
400 mg / day for 3 month
Other Name: Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 and 75 years
  • French citizen
  • Signed consent for participation
  • No dental infection
  • No programmed dental surgery during the treatment
  • Effective contraception for women of childbearing potential
  • Patient with advanced otosclerosis defined by:
  • Slowly progressive uni or bilateral hearing loss
  • No past medical history of chronic otitis media
  • No past medical history of other causes of cochlear damage (significant surgical trauma with a 30 dB deterioration of bone conduction at 4000 Hz in postoperative period, sound trauma, barotrauma, ototoxic drugs)
  • Normal tympanic membranes
  • A conductive or mixed hearing loss
  • A moderate to severe hearing loss on at least one ear (average of thresholds at 500, 1000, 2000 and 4000 Hz) on air conduction between 30 and 90 dB.
  • Normal tympanometry or with a decreased peak
  • Absent ipsilateral stapedial reflex
  • As possible, intraoperative confirmation of stapediovestibular ankylosis
  • radiological confirmation if CT-scan before inclusion available

Exclusion Criteria:

  • Individuals not covered by the french public health insurance
  • Pure-tone average < 30 dB ou > 90 dB
  • Programmed stapes surgery during the observation period
  • Previous treatment by biphosphonate
  • Known intolerance to tiludronate
  • Other contraindications to tiludronate treatment:
  • allergy to biphosphonates
  • hypersensitivity to one of the excipients
  • severe renal failure (creatinine clearance < 30 mL/min)
  • juvenile Paget's disease
  • pregnancy and breastfeeding
  • galactose intolerance, lactase insufficiency, glucose-galactose malabsorption
  • Ongoing chemotherapy or radiotherapy or patient achieves of a cancer
  • Long-term systemic steroid treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617057

Locations
France
Beaujon Hospital
Paris, France, 92118
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Alexis BOZORG-GRAYELI, Pr Hôpital Général, CHU de Dijon
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01617057     History of Changes
Other Study ID Numbers: P081235
Study First Received: June 8, 2012
Last Updated: March 12, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
otosclerosis
inner ear
tiludronic acid

Additional relevant MeSH terms:
Otosclerosis
Ear Diseases
Otorhinolaryngologic Diseases
Tiludronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014