Effects of Bisphosphonates on OI-Related Hearing Loss

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Risedronate Oral Tablet
  Oral bisphosphonate

Первичные конечные точки

• Pure Tone Averages [Срок оценки: Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months]

Вторичные конечные точки (10)

• Speech Recognition Scores [Срок оценки: Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months]
• Word Recognition Scores [Срок оценки: Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months]
• Hearing Handicap Inventory Raw Score [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]
• Tinnitus Handicap Inventory Score [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]
• Dizziness Handicap Inventory Score [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]
• SF-36 Scale and Summary Scores [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]
• Pediatric Outcomes Data Collection Instrument (PODCI) Score [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]
• Adolescent Outcomes Questionnaire Score [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]
• DEXA Z-score [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]
• DEXA Bone Mineral Density [Срок оценки: Yearly (Baseline, 12, 24, 36, 48, 60 months)]

Критерии участия

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Hospital for Special Surgery — New York

Публикации

• 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
• 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
• Sillence D. Osteogenesis imperfecta: an expanding panorama of variants. Clin Orthop Relat Res. 1981 Sep;(159):11-25. PMID 7285446
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT04152551 · #2018-0700

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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