Bisphosphonates for Hearing Loss
Recruiting in Palo Alto (17 mi)
Overseen byCathleen Raggio, MD
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Hospital for Special Surgery, New York
Must be taking: Bisphosphonates
Disqualifiers: Family history hearing-loss, Pregnancy
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, if you are a child currently receiving bisphosphonate treatment, you will continue with it as part of the study.
What data supports the effectiveness of the drug Risedronate Oral Tablet for hearing loss?
Research suggests that bisphosphonates, like Risedronate, may help with hearing loss related to otosclerosis (a bone condition in the ear) by improving hearing outcomes without causing harm to the ear.
12345How is the drug Risedronate unique for treating hearing loss?
Risedronate is unique for treating hearing loss because it is a bisphosphonate, typically used for bone conditions like osteoporosis, and works by inhibiting bone resorption (breakdown). This is different from other hearing loss treatments, which usually do not involve bone-targeting drugs.
678910Eligibility Criteria
This trial is for individuals with type I Osteogenesis Imperfecta (OI) and hearing loss. Adults aged 18+ with mild hearing loss and children aged 6-17, whether currently on bisphosphonates or not, can join. Participants must have a Vitamin D level >30. Those with family history of non-OI related hearing loss or pregnant individuals cannot participate.Inclusion Criteria
My child is between 6 and 17 years old.
I am between 6 and 17 years old.
I have been diagnosed with mild hearing loss.
+8 more
Exclusion Criteria
My family has a history of hearing loss not due to OI or work.
ALL ARMS: Pregnancy
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Adults with type 1 OI receive Risedronate treatment; children observed for changes in hearing, quality of life, and bone density
63 months
Yearly visits for assessments
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 months
Participant Groups
The study tests the effects of Risedronate Oral Tablet, a bisphosphonate, on OI-related hearing loss in adults and observes its use in children already receiving it for orthopedic symptoms. It's a comparison between treated adults/children and untreated controls over approximately 5 years.
4Treatment groups
Experimental Treatment
Active Control
Group I: Adult Treatment ArmExperimental Treatment1 Intervention
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.
Group II: Adult Control ArmActive Control1 Intervention
Observational arm. Adults (18+ years) with type 1 OI. Changes in hearing, quality of life, and bone density will be monitored.
Group III: Child (Control Arm)Active Control1 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.
Group IV: Child (Bisphosphonate Arm)Active Control1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hospital for Special SurgeryNew York, NY
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Who Is Running the Clinical Trial?
Hospital for Special Surgery, New YorkLead Sponsor
Northwell HealthCollaborator
East River Medical ImagingCollaborator
The New York Community TrustCollaborator
References
Bisphosphonate-associated osteonecrosis of the auditory canal. [2013]Only rare cases of osteonecrosis of the auditory canal associated with bisphosphonates, have been published. Our results confirm that similar reports can also be encountered in databases of adverse drug reactions.
Third-generation bisphosphonates for treatment of sensorineural hearing loss in otosclerosis. [2021]To evaluate hearing outcomes in patients treated with third generation bisphosphonates for otosclerosis-related sensorineural hearing loss (SNHL).
External auditory canal and middle ear cholesteatoma and osteonecrosis in bisphosphonate-treated osteoporosis patients: a Danish national register-based cohort study and literature review. [2021]Long-term treatment with bisphosphonates against osteoporosis may cause atypical femur fractures and osteonecrosis of the jaw. Eight cases of bisphosphonate-associated osteonecrosis of the external auditory canal area are published. Based on Danish national registers, we report a time- and dose-dependent increased risk of cholesteatoma in osteoporosis patients treated with bisphosphonates.
Two Cases of External Auditory Canal Osteonecrosis in Patients on Antiresorptive Therapy for Osteoporosis. [2023]Bisphosphonates and denosumab have demonstrated overwhelmingly favorable skeletal benefit/risk profile in managing postmenopausal osteoporosis. External auditory canal osteonecrosis is a rare skeletal complication of antiresorptives previously described in 11 patients with bisphosphonate exposure and 1 bisphosphonate-naïve patient on denosumab. We present 2 patients who developed external auditory canal osteonecrosis while taking antiresorptives for postmenopausal osteoporosis; a 79-year-old asymptomatic bisphosphonate-naïve woman with 2-year exposure to denosumab, and a 64-year-old woman with otalgia after 5 years of risedronate and 5 years of denosumab treatment. Neither patient had previous exposure to glucocorticoids or local radiotherapy. Otoscopy performed by an ear/nose/throat (ENT) surgeon revealed exposed areas of bone in external auditory canal in both patients. Computed tomography of temporal bones found no evidence of bone erosion. Bone turnover markers were suppressed. Both patients ceased denosumab and were managed conservatively, with stable external auditory canal findings after 12 months. Although external auditory canal osteonecrosis is a rare skeletal complication of antiresorptive use, development of localizing symptoms in the ear should alert physicians to this rare clinical entity and prompt ENT surgical referral for early diagnosis and initiation of management.
Non-Ototoxic Local Delivery of Bisphosphonate to the Mammalian Cochlea. [2018]Local delivery of bisphosphonates results in superior localization of these compounds for the treatment of cochlear otosclerosis, without ototoxicity.
Oesophageal transit, disintegration and gastric emptying of a film-coated risedronate placebo tablet in gastro-oesophageal reflux disease and normal control subjects. [2019]Risedronate sodium is a pyridinyl bisphosphonate, proven effective for the treatment and prevention of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and Paget's disease of the bone.
Placebo-controlled, randomized, evaluator-blinded endoscopy study of risedronate vs. aspirin in healthy postmenopausal women. [2019]Bisphosphonates are effective treatments for osteoporosis. Since some primary amino bisphosphonates are associated with oesophageal injury, we conducted a study of the upper gastrointestinal effects of risedronate, a pyridinyl bisphosphonate.
Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations. [2019]Risedronate sodium is an orally active antiresorptive agent and a member of the pyridinyl class of bisphosphonates. It has been approved for the treatment of Paget's disease of the bone and is under development as a chronic therapy for the treatment and prevention of osteoporosis. A novel cellulose film-coated tablet formulation was developed to optimize esophageal transit of this bisphosphonate. The aim of the present study was to compare the esophageal transit of the film-coated tablet formulation of risedronate with its original gelatin capsule dose form. A total of 25 elderly, healthy volunteers (mean 66 years), who were dysphagia-free, participated in this randomized cross-over study. On separate occasions, volunteers swallowed radiolabeled placebo formulations with 50 ml water. Dynamic images with participants in a sitting position were recorded for 10 min using a gamma camera. Scintigraphic imaging showed a delay in esophageal transit (greater than 15 s) in 28% of patients in the capsule group but in none of the tablet group (P
Risedronate. [2018]Risedronate is a pyridinyl bisphosphonate that can be administered orally in lower dosages than other antiresorptive bisphosphonates. Like others of its class risedronate inhibits osteoclast-mediated bone resorption. In experimental models of osteoporosis, risedronate inhibited bone loss and improved trabecular architecture. In patients with Paget's disease, pain diminished or disappeared and serum alkaline phosphatase levels decreased after treatment with oral risedronate 30 mg/day for
Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. [2022]Bisphosphonates inhibit bone resorption and thus bone renewal by suppressing the recruitment and activity of osteoclasts thus shortening their life span. Recently three bisphosphonates, Pamidronate (Aredia; Novartis Pharmaceuticals, East Haven, NJ), Zoledronate (Zometa; Novartis Pharmaceuticals), and Alendronate (Fosamax; Merck Co, West Point, VA) have been linked to painful refractory bone exposures in the jaws.