Effects of Bisphosphonates on OI-Related Hearing Loss

Study Overview
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Brief Summary
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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.

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

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Drug: Risedronate Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult Treatment Arm<br>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<br>* Oral bisphosphonate<br>* Other names: actonel;|
| No Intervention: Child (Bisphosphonate Arm)<br>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)<br>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. | |
| No Intervention: Adult Control Arm<br>Observational arm. Adults (18+ years) with type 1 OI. Changes in hearing, quality of life, and bone density will be monitored. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Hearing Handicap Inventory Raw Score | Score 0-40. Lower score is better. Adults (self-reported) | Yearly (Baseline, 12, 24, 36, 48, 60 months) | 
| Tinnitus Handicap Inventory Score | Score 0-100. Lower score is better. Adults (self-reported). | Yearly (Baseline, 12, 24, 36, 48, 60 months) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| DEXA Z-score | Higher score is better. Relative Bone Density | Yearly (Baseline, 12, 24, 36, 48, 60 months) | 
| DEXA Bone Mineral Density | Higher score is better. Bone Mineral Density (grams/centimeter^2) | Yearly (Baseline, 12, 24, 36, 48, 60 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OI, hearing loss, bisphosphonate, skeletal dysplasia, brittle bone disorder, osteogenesis imperfecta