Effects of Bisphosphonates on OI-Related Hearing Loss

Osteogenesis Imperfecta Clinical Trial

Official title:

Effects of Bisphosphonates on OI-Related Hearing Loss: A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04152551
• Other study ID #: #2018-0700
• Status: Recruiting
• Phase: Phase 4
• Start date: November 2, 2019
• Est. completion date: November 2024

Study information

• Verified date: April 2024
• Source: Hospital for Special Surgery, New York
• Contact: Su Htwe
• Phone: (212)774-2355
• Email: htwes[@]hss.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 100 Years

Eligibility

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 (Adult Control Arm):

• Diagnosis of OI type I 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

Related Conditions & MeSH terms

• Deafness
• Hearing Loss
• Osteogenesis Imperfecta

Intervention

Drug:
• Risedronate Oral Tablet
Oral bisphosphonate

Locations

Country	Name	City	State
United States	Hospital for Special Surgery	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Hospital for Special Surgery, New York	East River Medical Imaging, Northwell Health, The New York Community Trust

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. Erratum In: Am J Med Genet A. 2015 May;167A(5):1178. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

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