Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000318280
Ethics application status
Approved
Date submitted
22/02/2018
Date registered
5/03/2018
Date last updated
4/10/2023
Date data sharing statement initially provided
4/10/2023
Date results information initially provided
4/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Intranasal insulin for treatment of delirium.
Scientific title
A phase 2 single site, double blind randomised placebo controlled trial of intranasal insulin for the management of delirium in patients over 65 years old.
Secondary ID [1] 294093 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Delirium 306673 0
Condition category
Condition code
Neurological 305773 305773 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nebulised intranasal insulin.

Drug: insulin detemir.
Dose: 20 international units twice daily.
Device: Nasal drug delivery device (ViaNase delivery device, Kurve Technology, Bothell, Washington).
Administration: 20 seconds both nostrils twice daily (8am and 8pm) assisted by registered nurse.
Duration: Commence within 48 hours of presentation to hospital. Stop when delirium resolved (48hours delirium free) or discharged from hospital.
Monitoring adherence: nurses will document on electronic medical record whether medication was able to be administered. Study team will audit successful doses administered for each patient.
Intervention code [1] 300373 0
Treatment: Drugs
Comparator / control treatment
Saline.

Drug: Normal saline (0.9% sodium chloride).
Dose: 0.2mL twice daily
Device: Nasal drug delivery device (ViaNase delivery device, Kurve Technology, Bothell, Washington).
Administration: 20 seconds both nostrils twice daily (8am and 8pm) assisted by registered nurse.
Duration: Commence within 48 hours of presentation to hospital. Stop when delirium resolved (48hours delirium free) or discharged from hospital.
Monitoring adherence: nurses will document on electronic medical record whether medication was able to be administered. Study team will audit successful doses administered for each patient.
Control group
Placebo

Outcomes
Primary outcome [1] 304848 0
Duration of delirium assessed using the Confusion Assessment Method (CAM) assessed by trained study researcher or expert Geriatrician assessment.
Timepoint [1] 304848 0
Time point: The CAM will be conducted daily until delirium resolves (48hours CAM negative). Patients discharged with delirium will continue to be reviewed daily by a researcher in the home environment for up to one week.
Secondary outcome [1] 343351 0
Length of hospital stay.
Based on a review of electronic medical records which state the date and time of presentation to and discharge from the hospital.
Timepoint [1] 343351 0
At discharge from hospital.
Secondary outcome [2] 343352 0
Severity of delirium, measured by Delirium Index (DI).
Timepoint [2] 343352 0
Daily until delirium resolves.
Secondary outcome [3] 343353 0
Adherence to study medication measured by the percentage of doses successfully administered.
Timepoint [3] 343353 0
Following resolution of delirium or discharge from hospital.
Secondary outcome [4] 343354 0
Hospital complications: measured by the sum of hospital-acquired complications during admission. Relevant hospital-acquired complications prespecified from Australia Commission on Safety and Quality in Health Care list. These will include pressure injuries, falls (with or without injury), healthcare-associated infection, respiratory complications (aspiration pneumonia) and new persistent incontinence.
Timepoint [4] 343354 0
At discharge from hospital
Secondary outcome [5] 343355 0
Mortality rates.
This will be assessed based on hospital medical records during the inpatient admission. For post-discharge follow up, a telephone call will be made to the person responsible and hospital medical records will also be reviewed.
Timepoint [5] 343355 0
During admission and follow up 6 months post-discharge from hospital.
Secondary outcome [6] 343358 0
New admission to a residential aged care facility.
This will be classified as discharge to a residential aged care facility in a participant living at home prior to enrolment in the trial. Data will be obtained from electronic medical records during admission and phone call on follow up.
Timepoint [6] 343358 0
During admission and follow up 6 months post-discharge from hospital.
Secondary outcome [7] 343359 0
Cognitive function at 6 months follow up measured by Mini-Mental Status Examination, Digit Span, Mental Control, Trail making test A and B, clock drawing test, verbal fluency and five word memory test.
Timepoint [7] 343359 0
6 months post-discharge from hospital follow up.
Secondary outcome [8] 343360 0
Independence at 6 months follow up measured by Barthel Index and Instrumental ADL index.
Timepoint [8] 343360 0
6 months post-discharge from hospital follow up.
Secondary outcome [9] 343449 0
Use of antipsychotics measured by total equivalence dose of antipsychotic administered during admission and median daily dose administered.
The medication type, dose and frequency of administration will be recorded and converted into an equivalence antipsychotic based on previously published data.
Timepoint [9] 343449 0
Review at discharge from hospital.

Eligibility
Key inclusion criteria
Prevalent delirium (presenting to hospital with delirium), regardless of cause diagnosed using the confusion assessment method.
Receiving inpatient care at the Prince of Wales Hospital.
Age >65 years.
Enrolment within 48hours of admission.
Informed consent obtained.
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Haemodynamic instability requiring inotropic support.
Expected prognosis is less than 7 days lifespan by admitting medical consultant opinion.
Allergy to insulin detemir formulation.
Structural abnormality precluding the use of a nasal drug delivery device.
Consent unable to be obtained.
Previous enrolment in the trial.
Proven or suspected COVID-19

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the allocation schedule who is at a central administration site (pharmacy).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomization using a computer algorithm.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power analysis (with a 5% significance and 80% power) was performed using published data which shows the mean duration of delirium clustered around 7 days in Geriatric ward populations. Power calculation demonstrates reducing delirium duration by two days (from 8 days to 6 days) requires 36 in each arm for a total of 72 patients. Allowing for a 30% dropout rate, a total of 100 participants will be sought.

Statistical analysis plans will be sealed prior to unblinding.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/03/2018
Actual
12/03/2018
Date of last participant enrolment
Anticipated
27/07/2019
Actual
27/03/2023
Date of last data collection
Anticipated
27/12/2019
Actual
15/09/2023
Sample size
Target
100
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 10066 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 21586 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 298728 0
Charities/Societies/Foundations
Name [1] 298728 0
JJ Mason and HS Williams Memorial Foundation (The Mason Foundation)
Country [1] 298728 0
Australia
Funding source category [2] 298730 0
Charities/Societies/Foundations
Name [2] 298730 0
The Julia Lowy Foundation
Country [2] 298730 0
Australia
Funding source category [3] 298756 0
Charities/Societies/Foundations
Name [3] 298756 0
The Harry Triguboff Foundation
Country [3] 298756 0
Australia
Primary sponsor type
Individual
Name
A/Prof Gideon A Caplan
Address
Department of Geriatric Medicine
South Wing- Edmund Blackett Building
Prince of Wales Hospital
Barker St, Randwick, NSW 2031
Country
Australia
Secondary sponsor category [1] 297933 0
Individual
Name [1] 297933 0
Dr Anita Nitchingham
Address [1] 297933 0
Department of Geriatric Medicine
South Wing- Edmund Blackett Building
Prince of Wales Hospital
Barker St, Randwick, NSW 2031
Country [1] 297933 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299672 0
South Eastern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 299672 0
Room G71 East Wing
Edmund Blackett Building
Prince of Wales Hospital
Randwick NSW 2031
Ethics committee country [1] 299672 0
Australia
Date submitted for ethics approval [1] 299672 0
Approval date [1] 299672 0
22/05/2017
Ethics approval number [1] 299672 0
16/320 (HREC/16/POWH/653)

Summary
Brief summary
Delirium is a common medical condition characterised by sudden and fluctuating disturbances in thinking, attention and consciousness. Affecting up to one in four hospitalised older people, delirium is considered a medical emergency because it causes premature death, admission to nursing home, dementia, longer stays in hospital and loss of independence. Currently, there are no licenced treatments for people with delirium for use in the Emergency Department or on hospital wards. The most popular off-licence treatment for delirium, antipsychotics, was recently shown to worsen symptoms and increase death. The need to discover safe treatments is urgent.

Recent research has identified significant changes in brain glucose (sugar) metabolism during an episode of delirium. Insulin receptors are widely expressed in the brain and insulin delivered via nasal spray (intranasal insulin) has been shown to increase glucose uptake in the brain. Intranasal insulin has been tested in older people and was found to be safe and may be associated with an improved cognitive function. The effect of intranasal insulin in delirium has previously not been evaluated.

We will study intranasal insulin to treat delirium in people coming to the Emergency Department at Prince of Wales Hospital. We will conduct a randomised double blind placebo controlled trial of 100 patients and scientifically evaluate the effect of intranasal insulin compared to salt water (saline). Neither the Doctor nor the study participant knows which treatment the participant is receiving. Patients will be reviewed daily by an Aged Care Specialist while they have delirium and be followed up at six months. The primary objective is to evaluate if intranasal insulin reduces the duration of delirium in hospitalised older adults. Secondary objectives will assess if intranasal insulin decreases the length of hospital stay, reduces the percentage of people discharged to residential care, reduces death during admission and at six months, reduces delirium severity and preserves cognitive status six months post-delirium.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81242 0
A/Prof Gideon A Caplan
Address 81242 0
Department of Geriatric Medicine
South Wing Edmund Blackett Building
The Prince of Wales Hospital
Barker Street
Randwick NSW 2031
Country 81242 0
Australia
Phone 81242 0
+61292824252
Fax 81242 0
Email 81242 0
[email protected]
Contact person for public queries
Name 81243 0
A/Prof Gideon A Caplan
Address 81243 0
Department of Geriatric Medicine
South Wing Edmund Blackett Building
The Prince of Wales Hospital
Barker Street
Randwick NSW 2031
Country 81243 0
Australia
Phone 81243 0
+61292824252
Fax 81243 0
Email 81243 0
[email protected]
Contact person for scientific queries
Name 81244 0
A/Prof Gideon A Caplan
Address 81244 0
Department of Geriatric Medicine
South Wing Edmund Blackett Building
The Prince of Wales Hospital
Barker Street
Randwick NSW 2031
Country 81244 0
Australia
Phone 81244 0
+61292824252
Fax 81244 0
Email 81244 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The complete de-identified data set will be stored on the University of New South Wales Data Archive
When will data be available (start and end dates)?
The data will be available on at the completion of the trial. No end date determined.
Available to whom?
The dataset will be made available on a case-by-case basis at the discretion of the Primary Sponsor to researchers who provide a methodologically sound proposal.
Available for what types of analyses?
For meta-analyses or methodologically sound research purposes.
How or where can data be obtained?
Data can be accessed by contacting: [email protected] OR [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20580Study protocol  [email protected]
20581Statistical analysis plan  [email protected]



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo Not yet published.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIntranasal insulin for treatment of delirium in older hospitalised patients: Study protocol for a randomised controlled trial.2021https://dx.doi.org/10.1136/bmjopen-2021-050765
N.B. These documents automatically identified may not have been verified by the study sponsor.