Ototoxic Hearing LossPhase 2NCT05129748
Efficacy of Sodium Thiosulfate and Mannitol in Reducing Ototoxicity in Adult Patients Receiving Cisplatin Chemotherapy
A Phase 2 study testing Sodium Thiosulfate + Mannitol in people with Ototoxic Hearing Loss, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
One common side effect of cisplatin chemotherapy is ototoxicity. The drugs sodium thiosulfate and mannitol may protect against cisplatin-induced hearing loss. Specifically, sodium thiosulfate has been found to protect the cells in the inner ear, and may therefore prevent hearing loss. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ototoxic Hearing Loss
- What is being tested?
- Sodium Thiosulfate + Mannitol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 1 siteCanada
- Study dates
- 15 Feb 2023to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undertaking systemic cisplatin therapy as part of their cancer treatment
- Age ≥ 18
- Willing to provide informed consent
- ECOG performance status 0-2
- For female of child-bearing potential, a negative pregnancy test (beta-HCG) prior to study treatment is required
- Any patient who is of reproductive age should provide written agreement to use adequate contraception for the duration of the trial
Who cannot join
- Age less than 18
- Preexisting severe to profound sensorineural hearing loss (unilateral or bilateral) (speech reception threshold >70dB, or word recognition score <50%) as confirmed with an audiogram
- History of Meniere's or fluctuating hearing loss
- Asymmetrical hearing loss (bone conduction threshold difference of: (a) 20 dB threshold difference at a single frequency, (b) 15 dB threshold difference at 2 frequencies, (c) 10 dB threshold difference at 3 frequencies
- Abnormal renal function (creatinine clearance <60 ml/min)
- Abnormal liver function (liver function tests (ALT and ALP) >2.5 times upper limit of normal without liver metastasis and >5 times upper limit of normal with liver metastasis
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- Previous hypersensitivity to STS or mannitol
- Pregnant and/or nursing women
- Patient unable to follow the protocol for any reason
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario
Yasmeen Aboulhawa, yasmeen.aboulhawa@sri.utoronto.ca
Trung Le
About this study
Official title: A Multicenter Randomized Phase II Clinical Trial of the Efficacy of Sodium Thiosulfate and Mannitol in Reducing Ototoxicity in Adult Patients Receiving Cisplatin Chemotherapy
One common side effect of cisplatin chemotherapy is ototoxicity. The drugs sodium thiosulfate and mannitol may protect against cisplatin-induced hearing loss. Specifically, sodium thiosulfate has been found to protect the cells in the inner ear, and may therefore prevent hearing loss. Mannitol can help sodium thiosulfate enter the inner ear, and ponteially increase the effectiveness of sodium thiosulfate. This study aims to assess the efficacy of sodium thiosulfate and mannitol to reduce the hearing impairment caused by cisplatin chemotherapy.
Read the detailed description
Randomized phase II clinical trial: with 1:1 randomization between cisplatin alone, and cisplatin + sodium thiosulfate and mannitol. Participants will first be recruited into a 2-year pilot feasibility study of 24 patients (12 in each arm). The pilot study will be performed to evaluate the feasibility of the trial as defined by the following factors: treatment outcomes, occurrence of adverse events, logistics of treatment delivery, as well as dropout and recruitment rates. The results from the pilot study will support the safety, efficacy, and effectiveness of the sodium thiosuldate and mannitol treatment, confirm feasibility using the factors mentioned above, and serve as an earlier-phase developmental function to enhance the probability of success of the subsequent clinical trial. Participants will complete various pre-treatment hearing tests. Participants will receive sodium thiosulfate and mannitol 4 - 8 hours following chemotherapy treatment. The control group will not receive the experimental intervention. Follow-up hearing tests will be performed at select time intervals following completion of their cancer treatment.
- Conditions
- Ototoxic Hearing Loss
- Being tested
- Sodium Thiosulfate + Mannitol
- Keywords
- Hearing Loss, Deafness, Cisplatin-induced Ototoxicity, Sensorineural hearing loss, Ear diseases, Sodium Thiosulfate
- Medical subject headings
- Hearing Loss, Deafness, Hearing Loss, Sensorineural, Ear Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium Thiosulfate + MannitolDrug
Drug delivery will be sequential, where Mannitol will be infused over 30 minutes and Sodium Thiosulfate will be infused over 15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol | Experimental | Participants will receive the standard of care (cisplatin-based chemotherapy) plus the experimental treatment of Sodium Thiosulfate and Mannitol. Both drugs will be administered IV 4 - 8 hours following chemotherapy treatment, as part of post-chemotherapy hydration. Receives: Drug: Sodium Thiosulfate + Mannitol |
| Standard Cisplatin-based Chemotherapy | No intervention | Participants will receive the standard of care (cisplatin-based chemotherapy) only. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in hearing threshold with sodium thiosulfate and mannitol administration
The primary outcome measure of this study will be a comparison of hearing loss between the control and experimental groups. More specifically, each ear will be scored as having hearing loss if there is a greater than 10dB hearing loss in three contiguous frequencies. This will be measured via threshold hearing tests.
Measured: 2 months
Secondary outcomes (4)
To monitor potential oncological impact of sodium thiosulfate and mannitol on long-term renal clearance
Participants will be monitored for renal function via serum creatinine (umol/L) and creatinine clearance (ml/min).
Measured: 12 months
To monitor potential oncological impact of sodium thiosulfate and mannitol on disease free survival
Participants will be monitored for disease free survival via cancer staging details and clinical prognosis
Measured: 12 months
To monitor potential oncological impact of sodium thiosulfate and mannitol on overall survival
Participants will be monitored for overall survival via time in months
Measured: 12 months
To assess the short and long-term adverse event reporting from combination of sodium thiosulfate, mannitol and cisplatin.
To determine the causality of adverse events and serious adverse events and grading according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2021
- Study start15 Feb 2023
- Primary completionJan 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ototoxic Hearing LossStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 randomization between cisplatin alone, and cisplatin, sodium thiosulfate and mannitol.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05129748
- Sponsor's protocol ID
- 1818
- Status last verified
- Apr 2023
- First submitted
- 3 Nov 2021
- Last updated
- 14 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Phase II Clinical Trial of the Efficacy of Sodium Thiosulfate and Mannitol in Reducing Ototoxicity in Adult Patients Receiving Cisplatin Chemotherapy
- ClinicalTrials.gov ID
- NCT05129748
- Acronym / sponsor ID
- 1818
- Conditions
- Ototoxic Hearing Loss
- Keywords
- Hearing Loss, Deafness, Cisplatin-induced Ototoxicity, Sensorineural hearing loss, Ear diseases, Sodium Thiosulfate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 15 Feb 2023 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 22 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One common side effect of cisplatin chemotherapy is ototoxicity. The drugs sodium thiosulfate and mannitol may protect against cisplatin-induced hearing loss. Specifically, sodium thiosulfate has been found to protect the cells in the inner ear, and may therefore prevent hearing loss. Mannitol can help sodium thiosulfate enter the inner ear, and ponteially increase the effectiveness of sodium thiosulfate. This study aims to assess the efficacy of sodium thiosulfate and mannitol to reduce the hearing impairment caused by cisplatin chemotherapy.
Detailed description
Randomized phase II clinical trial: with 1:1 randomization between cisplatin alone, and cisplatin + sodium thiosulfate and mannitol. Participants will first be recruited into a 2-year pilot feasibility study of 24 patients (12 in each arm). The pilot study will be performed to evaluate the feasibility of the trial as defined by the following factors: treatment outcomes, occurrence of adverse events, logistics of treatment delivery, as well as dropout and recruitment rates. The results from the pilot study will support the safety, efficacy, and effectiveness of the sodium thiosuldate and mannitol treatment, confirm feasibility using the factors mentioned above, and serve as an earlier-phase developmental function to enhance the probability of success of the subsequent clinical trial. Participants will complete various pre-treatment hearing tests. Participants will receive sodium thiosulfate and mannitol 4 - 8 hours following chemotherapy treatment. The control group will not receive the experimental intervention. Follow-up hearing tests will be performed at select time intervals following completion of their cancer treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 1:1 randomization between cisplatin alone, and cisplatin, sodium thiosulfate and mannitol.
| Arm | Type | Receives |
|---|---|---|
| Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol | Experimental | Drug: Sodium Thiosulfate + MannitolParticipants will receive the standard of care (cisplatin-based chemotherapy) plus the experimental treatment of Sodium Thiosulfate and Mannitol. Both drugs will be administered IV 4 - 8 hours following chemotherapy treatment, as part of post-chemotherapy hydration. |
| Standard Cisplatin-based Chemotherapy | No intervention | –Participants will receive the standard of care (cisplatin-based chemotherapy) only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients undertaking systemic cisplatin therapy as part of their cancer treatment
- Age ≥ 18
- Willing to provide informed consent
- ECOG performance status 0-2
- For female of child-bearing potential, a negative pregnancy test (beta-HCG) prior to study treatment is required
Key exclusion criteria (9 listed)
- Age less than 18
- Preexisting severe to profound sensorineural hearing loss (unilateral or bilateral) (speech reception threshold >70dB, or word recognition score <50%) as confirmed with an audiogram
- History of Meniere's or fluctuating hearing loss
- Asymmetrical hearing loss (bone conduction threshold difference of: (a) 20 dB threshold difference at a single frequency, (b) 15 dB threshold difference at 2 frequencies, (c) 10 dB threshold difference at 3 frequencies
- Abnormal renal function (creatinine clearance <60 ml/min)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium Thiosulfate + MannitolDrug delivery will be sequential, where Mannitol will be infused over 30 minutes and Sodium Thiosulfate will be infused over 15 minutes. | Drug | Standard Cisplatin-based Chemotherapy + Sodium Thiosulfate + Mannitol |
Primary outcome
Improvement in hearing threshold with sodium thiosulfate and mannitol administration
Time frame: 2 months
The primary outcome measure of this study will be a comparison of hearing loss between the control and experimental groups. More specifically, each ear will be scored as having hearing loss if there is a greater than 10dB hearing loss in three contiguous frequencies. This will be measured via threshold hearing tests.
4 secondary outcomes
To monitor potential oncological impact of sodium thiosulfate and mannitol on long-term renal clearance
Time frame: 12 months
To monitor potential oncological impact of sodium thiosulfate and mannitol on disease free survival
Time frame: 12 months
To monitor potential oncological impact of sodium thiosulfate and mannitol on overall survival
Time frame: 12 months
To assess the short and long-term adverse event reporting from combination of sodium thiosulfate, mannitol and cisplatin.
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Individual participant dataSharing planned: No
Related trials for Ototoxic Hearing Loss
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Ototoxic Hearing Loss, Ototoxicity, Drug-Induced
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The Effect of Cancer Treatments on Speech Perception in Noise, Cognition, and Hearing-Related Quality of Life
Cancer, Hearing Loss Ototoxic
RecruitingObservational study
Ototoxicity in Patients With MoM Hip Bearings
Ototoxic Hearing Loss, Cobalt Poisoning
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium Thiosulfate + Mannitol in people with Ototoxic Hearing Loss, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yasmeen Aboulhawa (1-416-480-6100 ext. 85392, yasmeen.aboulhawa@sri.utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in hearing threshold with sodium thiosulfate and mannitol administration (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.