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Trial registered on ANZCTR


Registration number
ACTRN12617000273381
Ethics application status
Approved
Date submitted
15/02/2017
Date registered
22/02/2017
Date last updated
4/02/2020
Date data sharing statement initially provided
4/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the relationship between response to an olfactory stress test and level of cognitive decline in older adults.
Scientific title
Evaluating the relationship between response to an olfactory stress test and level of cognitive decline in older adults.
Secondary ID [1] 290876 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
OST Study Phase 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ALZHEIMER'S DISEASE 301510 0
Cognitive Impairment, Cognitive decline 301511 0
Condition category
Condition code
Neurological 301223 301223 0 0
Alzheimer's disease
Neurological 301767 301767 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is designed to determine the extent to which olfactory testing, performed conventionally, and also the change in olfaction following an intranasal anticholinergic challenge, is associated with cognitive decline.
Study participants returning to Phase 2 of the study will be assessed for cognitive change now that 4 years has passed.
Participants will receive two mail out surveys used in Phase 1.
Participants who are eligible will participate in two visits.
Visit 1 (duration 3-3.5 hours): Like Phase 1, participants will complete the Audio Recorded Cognitive Screen (ARCS), complete a series of questionnaires regarding medical history and cognition, and complete two smell tests.
Smell Test 1: University of Pennsylvania Smell Identification Test (UPSIT). Participants are asked to identify odours from a scratch and sniff booklet. Twenty items of the UPSIT will be administered prior to atropine being administered. After 45 minutes we will test with the remaining 20 items of the UPSIT.
Smell Test 2 (following Smell Test 1): Sniffin sticks are used as a test of nasal chemosensory performance that is based on pen-like odour-dispensing devices. Participants will be presented with 16 pens at an interval of 30 seconds. Each participant is provided with a sheet of paper which describes 16 lists with 4 items each. Participants have to identify the item that best describes the presented odour. Test repeated at 45 minute interval, following atropine administration. Upon completion participants will be asked to complete a sleep diary for 1 week and wear an accelerometer during that period.

Visit 2 (within 7 days of visit 1, duration 1.5 hours): Participants will attend a clinic appointment for a Neuropsychological Test Battery (NTB). The NTB is comprised of the following tests: California Verbal Learning Test (CVLT), WMS IV Visual Reproduction Test, WAIS IV Block Design, Similarities and Digit Span, WAIS IV Symbol Search & Coding, Colour Word Interference Task and the test of Premorbid Functioning.

The major implication and novelty of this study lies in the new technique for administering 1% atropine during Visit 1. . This involves using a soft narrow tube attached to a syringe that the study participant gently inserts into their left nostril until they feel the end touching the inside of their nose, which occurs as it reaches the olfactory cleft, where we wish to deposit atropine. The participant then squirts the syringe to deposit a measured dose (0.05 ml) of the atropine.
Intervention code [1] 297210 0
Early detection / Screening
Comparator / control treatment
In Phase 1, eligible participants completed a variety of assessments between 1/3/2013 - 20/11/2014. The Hunter New England Human Research Ethics committee granted ethical approval on 18/05/2012 reference number HNEHREC 12/04/18/5.05. University of Newcastle Research Office Reference number: G1100221

Assessments included:
Postal Surveys - Informant Questionnaire, Functional Activities Questionnaire
Smell Tests conducted pre and post (UPSIT, Sniffin Sticks) 1% atropine administration
Audio Recorded Cognitive Screen (ARCS)
Medical Assessment
Blood Tests
Physical Exercise Assessment via Accelerometers.

At Phase 1
Diagnoses (normal/cognitive impairment, aetiological) was based on clinical assessment, ARCS performance (worse than 1.5 SD below norms defining abnormality for any cognitive domain), and history of functional impairment due to cognitive problems, We applied DSM V and 2011 McKhann et al. criteria for AD, and NINDS-AIREN criteria for vascular dementia. Imaging evidence of vascular disease from MRIs was considered in assigning diagnoses.
Control group
Historical

Outcomes
Primary outcome [1] 300696 0
Cognitive decline on the Audio Recorded Cognitive Screen (ARCS)
Timepoint [1] 300696 0
At Visit 1 the Audio Recorded Cognitive Screen (ARCS) is administered as a single assessment prior to olfactory stress test. These results are compared to Phase 1 ARCS results. From the ARCS administered at Phase 1 and Phase 2 we will derive cognitive change scores.
Primary outcome [2] 300698 0

Phase 2
The Neuropsychological Test Battery will be used to inform Phase 2 diagnosis of incident dementia. Phase 2 will thus constitute a ‘gold standard’ diagnostic appraisal and in this way we will also avoid concerns of circularity when we assess the predictive properties of ARCS measures at Phase 1 for incident dementia/AD at Phase 2.

Definition of incident dementia due to Alzheimer's disease will be based on McKhann et al. 2011 criteria (Alzheimer’s & Dementia 7 (2011) 263–269).
Timepoint [2] 300698 0
Regular weekly consensus diagnostic conference, following Visit 2 Neuropsychological assessment.
Primary outcome [3] 301122 0
Change in olfactory (smell) performance on the Olfactory Stress Test.
Timepoint [3] 301122 0
At Visit 1, the olfactory stress test comprised of the University of Pennsylvania Smell Identification Test (UPSIT) and the Olfactory Sniffin Sticks. We will be using the two tests of Olfaction in this study. In both parts of the Olfactory Stress test, the UPSIT will be administered BEFORE the Sniffin Sticks. The smell performance of returning participants will be compared to Phase 1 results.
Secondary outcome [1] 330647 0
Diagnosis of Incident cognitive impairment will be made by consensus diagnostic conference.

Neuropsychological Test Battery (NTB) will be used to inform Phase 2 diagnosis of incident cognitive impairment (blind to ARCS scores). Phase 2 will thus constitute a ‘gold standard’ diagnostic appraisal and in this way we will also avoid concerns of circularity when we assess the predictive properties of ARCS measures at Phase 1 for incident cognitive impairment at Phase 2.

The diagnosis of Incident Cognitive Impairment will be based on the criteria outlined by Albert et al. (Alzheimer’s & Dementia 7 (2011) 270–279).

Timepoint [1] 330647 0
Consensus diagnostic conference, following Visit 2 Neuropsychological assessment.

Eligibility
Key inclusion criteria
Participants will be drawn from the Hunter Community Study (HCS), an established cohort of 3500 older individuals (aged 55-85 years old) randomly selected from the electoral roll, and recruited between 2004 and 2008.
Minimum age
65 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Does not have a minimum of grade 7 education
*Less than 65 years and older
*Inability to write.
*Inadequate visual acuity (5/36 or worse)
*Recent clinical stroke (within the last 6 months).
*Past history of severe traumatic brain injury
*Past olfactory tumour
*Active nasal/sinus disease

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis
Univariate and multivariate analyses will be conducted to assess the association of olfactory performance and change in olfactory performance with cognitive change, and incident dementia and incident cognitive impairment.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2017
Actual
28/06/2017
Date of last participant enrolment
Anticipated
20/12/2017
Actual
21/11/2018
Date of last data collection
Anticipated
22/12/2017
Actual
21/11/2018
Sample size
Target
279
Accrual to date
Final
279
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7468 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 7469 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 15297 0
2298 - Waratah
Recruitment postcode(s) [2] 15298 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 295305 0
Government body
Name [1] 295305 0
National Health & Medical Research Council
Country [1] 295305 0
Australia
Primary sponsor type
Individual
Name
Dr. Peter Schofield
Address
Hunter New England Local Health District Mental Health
Neuropsychiatry Services
5th Floor McAuley Centre
Calvary Mater Hospital Campus
Waratah, NSW 2298
Country
Australia
Secondary sponsor category [1] 294130 0
Individual
Name [1] 294130 0
Professor John Attia
Address [1] 294130 0
Hunter Medical Research Institute
Level 3 - the Pod
1 Kookaburra Close
New Lambton Heights
NSW 2305
Country [1] 294130 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296636 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 296636 0
Ethics committee country [1] 296636 0
Australia
Date submitted for ethics approval [1] 296636 0
30/11/2016
Approval date [1] 296636 0
03/04/2017
Ethics approval number [1] 296636 0
16/12/14/3.04

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71434 0
Dr Peter Schofield
Address 71434 0
Hunter New England Local Health District Mental Health
Neuropsychiatry Service
PO BOX 833
Newcastle NSW 2300
Country 71434 0
Australia
Phone 71434 0
+61 2 4033 5739
Fax 71434 0
+61 2 4033 5606
Email 71434 0
Peter.Schofield@hnehealth.nsw.gov.au
Contact person for public queries
Name 71435 0
Laura Miles
Address 71435 0
Hunter New England Local Health District Mental Health
Neuropsychiatry Service
PO BOX 833
Newcastle, NSW 2300
Country 71435 0
Australia
Phone 71435 0
+61 2 4033 5701
Fax 71435 0
+61 2 4033 5606
Email 71435 0
Laura.Miles@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 71436 0
Laura Miles
Address 71436 0
Hunter New England Local Health District Mental Health
Neuropsychiatry Service
PO BOX 833
Newcastle, NSW 2300
Country 71436 0
Australia
Phone 71436 0
+61 02 4033 5701
Fax 71436 0
+61 02 4033 5606
Email 71436 0
Laura.Miles@hnehealth.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Currently raw data is unavailable as it needs to be cleaned.


What supporting documents are/will be available?

No Supporting Document Provided



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.