Bisphosphonates for Hearing Loss

Overseen By Su Htwe

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Hospital for Special Surgery, New York

Must be taking: Bisphosphonates

Disqualifiers: Family history hearing-loss, Pregnancy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 63 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if bisphosphonates, specifically Risedronate Oral Tablet, can effectively treat hearing loss in individuals with Osteogenesis Imperfecta (OI type I), a condition often leading to early hearing issues. The trial includes adults with OI type I and mild hearing loss who will receive the treatment, along with a control group who will not. It also observes children with OI, both those already on bisphosphonate treatment and those who are not. Suitable candidates are adults with OI experiencing mild hearing loss or children with OI, regardless of whether they are receiving this treatment for bone issues. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for Risedronate Oral Tablet?

Research shows that Risedronate, the treatment under study, is generally well-tolerated. In studies on hearing issues like otosclerosis, patients maintained stable hearing over a year of using Risedronate, suggesting it does not worsen hearing problems.

The FDA has approved Risedronate for treating osteoporosis, indicating its safety for addressing bone loss in postmenopausal women. This approval provides extra confidence in its safety.

Common side effects in other uses include stomach upset and joint pain, but serious reactions are rare. For any concerns, discussing them with the research team or a doctor is advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using risedronate for hearing loss, particularly in patients with osteogenesis imperfecta (OI), because it represents a novel approach compared to traditional hearing loss treatments. Most standard treatments for hearing loss, like hearing aids or cochlear implants, focus on amplifying sound or directly stimulating the auditory nerve. Risedronate, however, is a bisphosphonate that targets bone metabolism, potentially addressing the underlying bone fragility in OI that could be affecting hearing. This unique mechanism offers the possibility of not just improving hearing but also enhancing overall bone health, which is particularly beneficial for individuals with OI.

What evidence suggests that bisphosphonate treatment might be effective for hearing loss?

Research has shown that medications called bisphosphonates, such as risedronate, effectively treat hearing problems related to otosclerosis. This condition resembles the hearing loss experienced by people with osteogenesis imperfecta (OI). Studies have found that bisphosphonates can help maintain stable hearing levels in cases of otosclerosis-related hearing loss. Additionally, patients using bisphosphonates have reported improvements in issues like tinnitus, a ringing in the ears. While more research is needed to understand their direct effects on hearing loss related to OI, the success in treating otosclerosis provides a strong basis for their potential use. In this trial, adult participants with type 1 OI and at least mild hearing loss will receive risedronate to evaluate its effects on hearing, quality of life, and bone density. This treatment has already shown promise in managing hearing loss in similar conditions. ^{1 3 6 7 8}

Who Is on the Research Team?

Cathleen Raggio, MD

Principal Investigator

Hospital for Special Surgery, New York

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

My family has a history of hearing loss not due to OI or work.

ALL ARMS: Pregnancy

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Risedronate Oral Tablet

Trial Overview

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.

How Is the Trial Designed?

Group I: Adult Treatment Arm Experimental Treatment 1 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 Arm Active Control 1 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 Control 1 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 Control 1 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.

Who Is Running the Clinical Trial?

Hospital for Special Surgery, New York

Lead Sponsor

Trials

257

Recruited

61,800+

Northwell Health

Collaborator

Trials

481

Recruited

470,000+

East River Medical Imaging

Collaborator

Trials

1

Recruited

100+

The New York Community Trust

Collaborator

Trials

7

Recruited

1,200+

Published Research Related to This Trial

External auditory canal osteonecrosis is a rare but serious complication associated with antiresorptive medications like denosumab and bisphosphonates, as demonstrated in two case studies involving patients with postmenopausal osteoporosis.

Both patients showed exposed bone in the external auditory canal but had stable conditions after stopping the medication and receiving conservative management, highlighting the importance of early diagnosis and ENT referral when symptoms arise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Cases of External Auditory Canal Osteonecrosis in Patients on Antiresorptive Therapy for Osteoporosis. Kumar, S., Diamond, T., Walton, J.[2023]

Long-term use of bisphosphonates for osteoporosis treatment is linked to a small but significant increase in the risk of cholesteatoma in the external auditory canal, particularly with higher doses and longer treatment durations, based on a study of 131,794 patients in Denmark.

Despite the increased risk of cholesteatoma, the overall incidence remains low, with no cases of bone destruction observed during the 7-year study period, indicating that while there are risks, they are relatively rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External auditory canal and middle ear cholesteatoma and osteonecrosis in bisphosphonate-treated osteoporosis patients: a Danish national register-based cohort study and literature review. Thorsteinsson, AL., Vestergaard, P., Eiken, P.[2021]

In a study involving 30 participants (15 with gastro-oesophageal reflux disease and 15 healthy controls), risedronate tablets showed similar rapid oesophageal transit, disintegration, and gastric emptying times in both groups, indicating that the medication is safe for use even in patients with GERD.

The design of the risedronate tablet, including its oval shape and film-coating, helps to promote quick movement through the oesophagus and reduces the risk of prolonged contact, which is beneficial for patients at risk of oesophageal irritation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oesophageal transit, disintegration and gastric emptying of a film-coated risedronate placebo tablet in gastro-oesophageal reflux disease and normal control subjects. Perkins, AC., Wilson, CG., Frier, M., et al.[2019]

In a study involving 80 healthy, postmenopausal women, risedronate (5 mg) did not cause any oesophageal or gastroduodenal ulcers, indicating its safety for upper gastrointestinal health.

In contrast, the aspirin group experienced significant gastrointestinal injuries, including gastric ulcers and erosions, highlighting risedronate's favorable gastrointestinal profile compared to aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled, randomized, evaluator-blinded endoscopy study of risedronate vs. aspirin in healthy postmenopausal women. Lanza, FL., Rack, MF., Li, Z., et al.[2019]

Risedronate, an oral bisphosphonate, effectively inhibits bone resorption and improves bone health, showing significant pain reduction and decreased alkaline phosphatase levels in patients with Paget's disease after just 3 months of treatment at 30 mg/day.

In postmenopausal women, risedronate at doses of 5 mg/day for up to 2 years increased bone mass, and 2.5 mg/day helped prevent bone loss during glucocorticoid treatment, with a safety profile similar to placebo regarding gastrointestinal and other adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risedronate. Goa, KL., Balfour, JA.[2018]

Bisphosphonates, while effective in inhibiting bone resorption, can lead to painful bone exposures in the jaws, with a significant incidence observed in patients treated for multiple myeloma and metastatic cancers, particularly with Zometa and Aredia.

Pre-therapy dental care is crucial in reducing the incidence of bisphosphonate-related jaw complications, and for those affected, a treatment regimen of antibiotics and antiseptic mouthwash is highly effective in managing pain, achieving a 90.1% success rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. Marx, RE., Sawatari, Y., Fortin, M., et al.[2022]

The study confirms that osteonecrosis of the auditory canal, a rare condition, can occur in patients taking bisphosphonates, a class of drugs commonly used to treat osteoporosis and other bone diseases.

This finding is supported by reports found in databases of adverse drug reactions, highlighting the need for awareness among healthcare providers regarding this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bisphosphonate-associated osteonecrosis of the auditory canal. Kharazmi, M., Hallberg, P., Persson, U., et al.[2013]

In a retrospective study of 10 patients with otosclerosis-related sensorineural hearing loss, treatment with third-generation bisphosphonates (risedronate or zoledronate) resulted in stabilization of hearing loss over an average follow-up of 13 months, with no major complications reported.

Out of the 19 ears treated, 2 patients showed actual improvement in hearing, indicating that these bisphosphonates may not only halt progression but could also enhance hearing outcomes in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third-generation bisphosphonates for treatment of sensorineural hearing loss in otosclerosis. Quesnel, AM., Seton, M., Merchant, SN., et al.[2021]

Local delivery of bisphosphonates, specifically through methods like placing alginate beads on the round window membrane or using microfluidic pump infusion, significantly improves drug localization and concentration in the cochlea compared to systemic delivery.

The study found no significant ototoxicity associated with either local or systemic delivery of the bisphosphonate 6-FAM-ZOL, suggesting that this treatment approach could be safe for patients with cochlear otosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Ototoxic Local Delivery of Bisphosphonate to the Mammalian Cochlea. Kang, WS., Sun, S., Nguyen, K., et al.[2018]

In a study involving 25 elderly volunteers, the new film-coated tablet formulation of risedronate showed significantly faster esophageal transit compared to the original gelatin capsule, with mean transit times of 3.3 seconds for tablets versus 23.8 seconds for capsules.

The film-coated tablets eliminated delays in esophageal transit seen in 28% of participants with the capsule formulation, indicating a safer and more effective option for patients, especially those with swallowing difficulties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations. Perkins, AC., Wilson, CG., Frier, M., et al.[2019]

Citations

1.

academic.oup.com

academic.oup.com/jbmrplus/article/9/10/ziaf134/8237221

Osteonecrosis of the external auditory canal in two patients on ...

In Case B, risedronate was commenced with reduction of bone markers and early healing of the auditory canal at 4 mo.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8823176/

Bisphosphonate therapy in otosclerosis: A scoping review

To date, the efficacy of bisphosphonate therapy for sensorineural hearing loss caused by otosclerosis remains inconclusive. CONFLICT OF INTEREST.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3442123/

Third generation bisphosphonates for treatment of ...

This pilot study demonstrates stable sensorineural hearing during an average 13 month follow up after zoledronate or risedronate treatment in otosclerosis ...

4.

link.springer.com

link.springer.com/article/10.1007/s00405-024-08935-z

Effectiveness of bisphosphonate for alleviating tinnitus ...

We demonstrated significant tinnitus improvement in cases treated with bisphosphonate compared to the control group.

5.

researchgate.net

researchgate.net/publication/384017829_Effectiveness_of_bisphosphonate_for_alleviating_tinnitus_associated_with_otosclerosis_a_prospective_case-control_study

Effectiveness of bisphosphonate for alleviating tinnitus ...

Conclusion Treatment with third‐generation bisphosphonates is associated with stability in otosclerosis‐related sensorineural hearing over 5‐ to ...

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/risedronate-oral-route/description/drg-20067115

Risedronate (oral route) - Side effects & dosage

Risedronate delayed-release tablets and tablets are used to prevent and treat osteoporosis (thinning of the bone) in women after menopause.

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2010/022560Orig1s000MedR.pdf

022560Orig1s000 - accessdata.fda.gov

• Risedronate 35 mg DR oral tablet after a 6 hour fast within 5 minutes after completing a standard dinner. No additional food was allowed for at least 4 ...

8.

ctv.veeva.com

ctv.veeva.com/study/effects-of-bisphosphonates-on-oi-related-hearing-loss

Effects of Bisphosphonates on OI-Related Hearing Loss

Changes in hearing, quality of life, and bone density will be monitored. Treatment: Drug: Risedronate Oral Tablet. Child (Bisphosphonate Arm).