ANZCTR - Registration

The ANZCTR website is back online for trial registration and updates. We apologise for any inconvenience caused while the site was inactive.

Please note that the ANZCTR will be unattended from Friday 18th April until Tuesday 22nd April due to the Easter long weekend. Submissions and updates will not be processed during that time.

Reset your password and enable multi-factor authentication (MFA)

For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.

Go to the Login page, click ‘reset password’ and follow the instructions.
Check your email for the link to set a new password.
Create a new password that meets requirements. New passwords must include at least one lowercase letter, one uppercase letter, one number and one special character (e.g. !#$%&@).
Return to the Login page and enter your new password. A verification code will be sent to your email.
Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12621000749808p

Ethics application status

Not yet submitted

Date submitted

15/04/2021

Date registered

15/06/2021

Date last updated

15/06/2021

Date data sharing statement initially provided

15/06/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Pharmacokinetics and safety of intratympanic adenosine receptor ligands

Scientific title

Pharmacokinetics and safety of intratympanic adenosine receptor ligands in adults undergoing elective translabyrinthine resection of vestibular schwannoma

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1265-4238

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Hearing loss

Condition category

Condition code

Ear

Deafness

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This is a phase I/IIA study, examining the pharmacokinetics and safety of intratympanic delivery of adenosine receptor ligands. Two ligands, Regadenoson and Istradefylline, already FDA approved for separate clinical uses, have demonstrated efficacy in animal models in prevention of hearing loss associated with trauma and certain chemotherapeutics. Regadenoson has been approved for use as a pharmacological stress agent for radionuclide myocardial perfusion imaging. Istradefylline is used in Parkinson’s disease as adjunctive treatment to levodopa/carbidopa
The intervention is to place the adenosine ligand within the middle ear at the commencement of a long neurosurgical operation. During the operation for resection of a vestibular schwannoma, the inner ear is opened routinely. We are then able to sample the perilymph, to assess the penetration of the adenosine ligand through the round window into the desired site of action, without added morbidity to the patient. As the patient is under an anaesthetic and is closely monitored we will be able to assess any safety concerns.
The dosage will be determined by a clinical pharmacologist based on prior in-vitro as well as animal studies. The adenosine ligand will be prepared for topical application in a polaxomer 407 gel by a pharmacist. The topical application will be transtympanically by an ENT surgeon.
There are two adenosine ligands being studied, Istradefyline and Regadenoson. One of these will be randomly assigned to each patient.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Incidence of adverse events as assessed by patient medical records.

Timepoint [1]

48 hours post intervention

Secondary outcome [1]

Establishing the pharmacokinetics of adenosine ligands delivered intratympanically, in particular its absorption through the round window into the perilymph We will measure Cmax, Tmax, AUC, clearance and T1/2 for plasma and perilymph

Timepoint [1]

Baseline, 30, 60, 120, 240 minutes post intervention

Eligibility

Key inclusion criteria

Patients undergoing elective translabyrithine resection of vestibular schwannoma

Minimum age

18 Years

Maximum age

99 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

i. Unstable cardiac disease (Arrhythmias, recent MI/stent)
ii. Renal impairment (Creatinine >100 umol/L)

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Not applicable

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Not applicable

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Phase 1 / Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

5/07/2021

Actual

Date of last participant enrolment

Anticipated

3/07/2023

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Canterbury

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Eisdell Moore Centre

Address [1]

22-30 Park Avenue, Grafton, Auckland 1023

Country [1]

New Zealand

Primary sponsor type

Charities/Societies/Foundations

Name

Eisdell Moore Centre

Address

22-30 Park Avenue, Grafton, Auckland, 1023

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Not yet submitted

Ethics committee name [1]

Health Research Council of New Zealand

Ethics committee address [1]

Level 3 - ProCARE Building, Grafton Mews, at 110 Stanley Street (GPS: 50 Grafton Road), Grafton, Auckland 1010

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

25/06/2021

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Sensorineural hearing loss following chemotherapy or ear surgery is common and significantly impairs patients’ quality of life. A number of otoprotective agents have shown promise in animal models and the next step is to translate these into clinical use. 
We have identified two otoprotective agents which act on the adenosine A2a receptor (A2AR) both of which are FDA approved and have established safety profiles. Istradefylline, used in Parkinson’s disease, reduces deafferentation of inner hair cells and improves the survival of afferent synapses after excitotoxic injury. Regadenoson, used as a cardiac stimulant in myocardial perfusion tests, also has strong anti-inflammatory effects in the cochlea.
Intratympanic administration of these drugs minimises any potential systemic side effects and provides adequate concentrations in the cochlea, especially the basal cochlea which is more susceptible to injury. Slow release of the drug within the middle ear permits better diffusion across the round window membrane. Poloxamer 407 gel has been used as a slow delivery vehicle both in animal studies and clinically. We plan to suspend the adenosine receptor ligands in this delivery vehicle. 
We aim to study the pharmacokinetic properties of both of these agents. First, in vitro experiments will measure drug elution from the gel over time to establish peak drug concentrations and duration. Then in patients already having their inner ear opened we will deliver a trans-tympanic injection of these agents and measure both the perilymph and plasma levels at different time points to help establish therapeutic concentrations and safety profiles.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Michael Bergin

Address

Department of Otolaryngology Head and Neck Surgery, Christchurch Hospital, Private Bag 4710, Christchurch 8140

Country

New Zealand

Phone

+64 0276074601

Fax

[email protected]

Contact person for public queries

Name

Michael Bergin

Address

Department of Otolaryngology Head and Neck Surgery, Christchurch Hospital, Private Bag 4710, Christchurch 8140

Country

New Zealand

Phone

+64 0276074601

Fax

[email protected]

Contact person for scientific queries

Name

Michael Bergin

Address

Department of Otolaryngology Head and Neck Surgery, Christchurch Hospital, Private Bag 4710, Christchurch 8140

Country

New Zealand

Phone

+64 0276074601

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

Yes

Will there be any conditions when requesting access to individual participant data?

Persons/groups eligible to request access:
• Data will be available to researchers only who provide a methodologically sound proposal

Conditions for requesting access:
• -

What individual participant data might be shared?

• Individual participant date underlying published results only

What types of analyses could be done with individual participant data?

• Only to achieve the aims of the approved proposal

When can requests for individual participant data be made (start and end dates)?

From:
The data will be retained for 10 years post the conclusion of the study. We aim to recruit till 03/07/23 and thus data will be available from then till 03/07/33.

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?

• The data will be retained by the primary investigator on a password protected personal computer. Contact with the leadinvestigator (Michael Bergin at [email protected]) requesting the data will thus need to be obtained

Are there extra considerations when requesting access to individual participant data?

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
11377	Study protocol					Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically