Effects of Bisphosphonates on OI-Related Hearing Loss

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StatusRecruiting

Keywords

Abstract

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.

Dates

Last Verified:	01/31/2020
First Submitted:	10/17/2019
Estimated Enrollment Submitted:	10/31/2019
First Posted:	11/04/2019
Last Update Submitted:	02/13/2020
Last Update Posted:	02/17/2020
Actual Study Start Date:	11/01/2019
Estimated Primary Completion Date:	10/31/2024
Estimated Study Completion Date:	10/31/2024

Condition or disease

Osteogenesis Imperfecta

Intervention/treatment

Drug: Adult Treatment Arm

Phase

Phase 4

Arm Groups

Arm	Intervention/treatment
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.	Drug: Adult Treatment Arm Oral bisphosphonate
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.

Eligibility Criteria

Ages Eligible for Study	6 Years To 6 Years
Sexes Eligible for Study	All
Accepts Healthy Volunteers	Yes
Criteria	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

Outcome

Primary Outcome Measures

1. Pure Tone Averages [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 Outcome Measures

1. Speech Recognition Scores [Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months]

Lowest volume participant can hear and understand speech (decibels)

2. Word Recognition Scores [Baseline, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months]

Percent of words participants correctly repeat in word recognition test (%)

3. Hearing Handicap Inventory Raw Score [Yearly (Baseline, 12, 24, 36, 48, 60 months)]

Score 0-40. Lower score is better. Adults (self-reported)

4. Tinnitus Handicap Inventory Score [Yearly (Baseline, 12, 24, 36, 48, 60 months)]

Score 0-100. Lower score is better. Adults (self-reported).

5. Dizziness Handicap Inventory Score [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.

6. SF-36 Scale and Summary Scores [Yearly (Baseline, 12, 24, 36, 48, 60 months)]

Score 0-100. Higher score is better. Adults (self-reported) quality-of-life survey.

7. Pediatric Outcomes Data Collection Instrument (PODCI) Score [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.

8. Adolescent Outcomes Questionnaire Score [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.

9. DEXA Z-score [Yearly (Baseline, 12, 24, 36, 48, 60 months)]

Higher score is better. Relative Bone Density

10. DEXA Bone Mineral Density [Yearly (Baseline, 12, 24, 36, 48, 60 months)]

Higher score is better. Bone Mineral Density (grams/centimeter^2)