Effects of Bisphosphonates on OI-Related Hearing Loss

Overview

Osteogenesis Imperfecta-related hearing loss usually occurs in individuals with mild (type I) OI and is much earlier in onset than age-related hearing loss, with the majority of individuals experiencing some minor hearing loss in their 20s. Bisphosphonates have been successfully used to treat otosclerosis, a common cause of hearing loss similar to OI-related hearing loss. As many individuals with OI-related hearing loss also present with otosclerosis and because of their mechanistic similarities, the investigators propose studying the effects of bisphosphonate treatment on individuals diagnosed with both OI type I and hearing loss, thereby determining its effectiveness as a potential treatment for hearing loss. The investigators will enroll 50 individuals diagnosed with type I OI, ages 18-100, who have documented hearing loss. The investigators will enroll 25 children (6-17 years of age) diagnosed with OI who are currently receiving bisphosphonate treatment as part of their care for orthopedic symptoms. The investigators will also observe 25 children (6-17 years of age) diagnosed with OI who are NOT currently receiving bisphosphonate treatment. The study duration is 63 months (approximately 5 years). Enrollment is anticipated to begin in November 2019.

Full Title of Study: “Effects of Bisphosphonates on OI-Related Hearing Loss: A Pilot Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2024

Interventions

  • Drug: Risedronate Oral Tablet
    • Oral bisphosphonate

Arms, Groups and Cohorts

  • Experimental: Adult Treatment Arm
    • Intervention treatment arm. Adults (18+ years) with type 1 OI. Must have at least mild hearing loss. Will receive Risedronate (35mg, 0-2x/week as clinically indicated) for duration of study. Changes in hearing, quality of life, and bone density will be monitored.
  • No Intervention: Child (Bisphosphonate Arm)
    • Observational (no investigational intervention) arm. Children (6-17 years) with any type of OI who are already receiving bisphosphonate treatment as standard of care treatment for orthopedic symptoms. Changes in hearing, quality of life, and bone density will be observed for the duration of the study.
  • No Intervention: Child (Control Arm)
    • Observational arm. Children (6-17 years) with any type of OI who are not receiving bisphosphonate treatment. Changes in hearing, quality of life, and bone density will be observed for the duration of the study.

Clinical Trial Outcome Measures

Primary Measures

  • Pure Tone Averages
    • Time Frame: Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months
    • Average hearing thresholds at 250, 500, 1000, 2000, 3000, 4000, 8000 Hertz

Secondary Measures

  • Speech Recognition Scores
    • Time Frame: Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months
    • Lowest volume participant can hear and understand speech (decibels)
  • Word Recognition Scores
    • Time Frame: Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months
    • Percent of words participants correctly repeat in word recognition test (%)
  • Hearing Handicap Inventory Raw Score
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Score 0-40. Lower score is better. Adults (self-reported)
  • Tinnitus Handicap Inventory Score
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Score 0-100. Lower score is better. Adults (self-reported).
  • Dizziness Handicap Inventory Score
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Score 0-100. Lower score is better. Adults (self-reported). Incidence and impact of vertigo in study population.
  • SF-36 Scale and Summary Scores
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Score 0-100. Higher score is better. Adults (self-reported) quality-of-life survey.
  • Pediatric Outcomes Data Collection Instrument (PODCI) Score
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Score 0-100. Lower score is better. Children (ages 6-10 years), parent-reported. Assessment of overall health and functioning.
  • Adolescent Outcomes Questionnaire Score
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Score 0-100. Lower score is better. Children (ages 11-17 years), parent- or self-reported. Assessment of overall health and functioning.
  • DEXA Z-score
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Higher score is better. Relative Bone Density
  • DEXA Bone Mineral Density
    • Time Frame: Yearly (Baseline, 12, 24, 36, 48, 60 months)
    • Higher score is better. Bone Mineral Density (grams/centimeter^2)

Participating in This Clinical Trial

Inclusion Criteria (Adult Treatment Arm):

  • Diagnosis of OI type I – Diagnosis of at least mild hearing loss (>20dB pure tone average) by audiogram testing – 18+ – Vitamin D level > 30 Inclusion Criteria (Child Observational Bisphosphonate Arm) – Diagnosis of OI – Age 6-17 years – Currently receiving bisphosphonate treatment as standard of care Inclusion Criteria (Child Observational No Treatment Arm) – Diagnosis of OI – Age 6-17 years – NOT receiving bisphosphonate treatment and will not receive bisphosphonate treatment for the duration of the study Exclusion Criteria (ALL ARMS): – Family history of hearing-loss (not related to OI or occupational hearing loss) – Pregnancy

Gender Eligibility: All

Minimum Age: 6 Years

Maximum Age: 100 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Hospital for Special Surgery, New York
  • Collaborator
    • The New York Community Trust
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Cathleen Raggio, MD, Principal Investigator, Hospital for Special Surgery, New York
  • Overall Contact(s)
    • Holly LoTurco, BS, (212)774-2355, loturcoh@hss.edu

References

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Sillence D. Osteogenesis imperfecta: an expanding panorama of variants. Clin Orthop Relat Res. 1981 Sep;(159):11-25.

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Quesnel AM, Seton M, Merchant SN, Halpin C, McKenna MJ. Third-generation bisphosphonates for treatment of sensorineural hearing loss in otosclerosis. Otol Neurotol. 2012 Oct;33(8):1308-14. doi: 10.1097/MAO.0b013e318268d1b3.

Kang WS, Nguyen K, McKenna CE, Sewell WF, McKenna MJ, Jung DH. Measurement of Ototoxicity Following Intracochlear Bisphosphonate Delivery. Otol Neurotol. 2016 Jul;37(6):621-6. doi: 10.1097/MAO.0000000000001042.

Ting TH, Zacharin MR. Hearing in bisphosphonate-treated children with osteogenesis imperfecta: our experience in thirty six young patients. Clin Otolaryngol. 2012 Jun;37(3):229-33. doi: 10.1111/j.1749-4486.2012.02476.x.

Patel RM, Nagamani SC, Cuthbertson D, Campeau PM, Krischer JP, Shapiro JR, Steiner RD, Smith PA, Bober MB, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Lee BH, Hart T, Sutton VR. A cross-sectional multicenter study of osteogenesis imperfecta in North America – results from the linked clinical research centers. Clin Genet. 2015 Feb;87(2):133-40. doi: 10.1111/cge.12409. Epub 2014 May 30.

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