Effects of Bisphosphonates on OI-Related Hearing Loss

NCT04152551 | Recruiting Phase 4 FDA Drug

• 1 other identifier: #2018-0700
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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 and age 18-100. 25 adults will be enrolled into the treatment arm and receive bisphosphonate treatment (must have at least mild hearing loss), while 25 adults will be enrolled into the control arm. 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.

Conditions

Osteogenesis Imperfecta

Keywords

hearing loss; bisphosphonate; skeletal dysplasia; brittle bone disorder; osteogenesis imperfecta; OI

Outcome Measures

Primary Outcomes (1)

• Pure Tone Averages

  Average hearing thresholds at 250, 500, 1000, 2000, 3000, 4000, 8000 Hertz

  Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months

Secondary Outcomes (10)

• Speech Recognition Scores

  Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months

• Word Recognition Scores

  Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months

• Hearing Handicap Inventory Raw Score

  Yearly (Baseline, 12, 24, 36, 48, 60 months)

• Tinnitus Handicap Inventory Score

  Yearly (Baseline, 12, 24, 36, 48, 60 months)

• Dizziness Handicap Inventory Score

  Yearly (Baseline, 12, 24, 36, 48, 60 months)

Study Arms (4)

Adult Treatment Arm

EXPERIMENTAL

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.

Drug: Risedronate Oral Tablet

Child (Bisphosphonate Arm)

NO INTERVENTION

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.

Child (Control Arm)

NO INTERVENTION

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.

Adult Control Arm

NO INTERVENTION

Observational arm. Adults (18+ years) with type 1 OI. Changes in hearing, quality of life, and bone density will be monitored.

Interventions

Risedronate Oral Tablet DRUG

Oral bisphosphonate

Also known as: actonel

Adult Treatment Arm

Eligibility Criteria

• Age: 6 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of OI type I
• Diagnosis of at least mild hearing loss (\>20dB pure tone average) by audiogram testing
• Vitamin D level \> 30
• Diagnosis of OI type I
• Diagnosis of OI
• Age 6-17 years
• Currently receiving bisphosphonate treatment as standard of care
• Diagnosis of OI
• Age 6-17 years
• NOT receiving bisphosphonate treatment and will not receive bisphosphonate treatment for the duration of the study

You may not qualify if:

• Family history of hearing-loss (not related to OI or occupational hearing loss)
• Pregnancy

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• The New York Community Trust: collaborator
• East River Medical Imaging: collaborator
• Northwell Health: collaborator

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

Related Publications (14)

• Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014 Jun;164A(6):1470-81. doi: 10.1002/ajmg.a.36545. Epub 2014 Apr 8.

  PMID: 24715559 BACKGROUND

• Pillion JP, Vernick D, Shapiro J. Hearing loss in osteogenesis imperfecta: characteristics and treatment considerations. Genet Res Int. 2011;2011:983942. doi: 10.4061/2011/983942. Epub 2011 Dec 14.

  PMID: 22567374 BACKGROUND

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

  PMID: 7285446 BACKGROUND

• Swinnen FK, De Leenheer EM, Coucke PJ, Cremers CW, Dhooge IJ. Audiometric, surgical, and genetic findings in 15 ears of patients with osteogenesis imperfecta. Laryngoscope. 2009 Jun;119(6):1171-9. doi: 10.1002/lary.20155.

  PMID: 19358256 BACKGROUND

• Berger G, Hawke M, Johnson A, Proops D. Histopathology of the temporal bone in osteogenesis imperfecta congenita: a report of 5 cases. Laryngoscope. 1985 Feb;95(2):193-9. doi: 10.1288/00005537-198502000-00014.

  PMID: 3918222 BACKGROUND

• Vincent R, Wegner I, Stegeman I, Grolman W. Stapedotomy in osteogenesis imperfecta: a prospective study of 32 consecutive cases. Otol Neurotol. 2014 Dec;35(10):1785-9. doi: 10.1097/MAO.0000000000000372.

  PMID: 24751750 BACKGROUND

• Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest. 1999 Nov;104(10):1363-74. doi: 10.1172/JCI6800.

  PMID: 10562298 BACKGROUND

• Rogers MJ, Frith JC, Luckman SP, Coxon FP, Benford HL, Monkkonen J, Auriola S, Chilton KM, Russell RG. Molecular mechanisms of action of bisphosphonates. Bone. 1999 May;24(5 Suppl):73S-79S. doi: 10.1016/s8756-3282(99)00070-8. No abstract available.

  PMID: 10321934 BACKGROUND

• Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008 Sep;83(9):1032-45. doi: 10.4065/83.9.1032.

  PMID: 18775204 BACKGROUND

• Kanzaki S, Ito M, Takada Y, Ogawa K, Matsuo K. Resorption of auditory ossicles and hearing loss in mice lacking osteoprotegerin. Bone. 2006 Aug;39(2):414-9. doi: 10.1016/j.bone.2006.01.155. Epub 2006 Mar 24.

  PMID: 16564235 BACKGROUND

• 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.

  PMID: 22935809 BACKGROUND

• 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.

  PMID: 27153329 BACKGROUND

• 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. No abstract available.

  PMID: 22708940 BACKGROUND

• 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.

  PMID: 24754836 BACKGROUND

MeSH Terms

Conditions

Osteogenesis Imperfecta; Hearing Loss; Mucopolysaccharidosis IV; Brittle Bone Disorder

Interventions

Risedronic Acid

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Cathleen Raggio, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Su Htwe

CONTACT

(212)774-2355; htwes@hss.edu

Erin Carter, MS, CGC

CONTACT

(212) 774-7332

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 25 adults with type 1 OI and diagnosed hearing loss will be treated with oral risedronate. 25 adults with type 1 OI will be enrolled into the control arm.

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: November 5, 2019
• Study Start: November 2, 2019
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)