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Trial registered on ANZCTR


Registration number
ACTRN12617001531303
Ethics application status
Approved
Date submitted
20/10/2017
Date registered
3/11/2017
Date last updated
8/02/2019
Date data sharing statement initially provided
6/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does intranasal oxytocin enhance emotions in dementia?
Scientific title
Pilot study: Intranasal oxytocin administration as a potential symptomatic intervention treatment to improve emotion recognition in patients with dementia
Secondary ID [1] 292123 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's disease 302405 0
Vascular dementia 303549 0
Condition category
Condition code
Neurological 301979 301979 0 0
Alzheimer's disease
Neurological 301980 301980 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In this 1 week, double-blind, randomised, placebo controlled crossover trial, all participants will be randomised to either an intranasal administered oxytocin (72 IU; One 36 IU doses of oxytocin/placebo per nostril twice daily) or placebo nasal spray (one dose per nostril twice daily) for one week. This is followed by a one week washout period and a further one week crossover period with the alternative medication.

Intervention adherence will primarily be monitored using a chart completed by the carer of the participant living with dementia, after each administration. Additionally, participants will be required to return empty medication packets at the end of each intervention week whereby the investigators will measure nasal-spray bottle weight to elucidate drug adherence
Intervention code [1] 297428 0
Treatment: Drugs
Comparator / control treatment
The participants in the placebo group will self-administer a saline mist nasal spray (one dose per nostril) twice daily for one week. The placebo saline mist nasal spray will be placed in an identical bottle to the active drug but only contain glycerol (2%); sorbitol crystaline powder (2 %); benzyl alcohol (0.9 %) and distilled water.
Control group
Placebo

Outcomes
Primary outcome [1] 301402 0
The ability to infer mental states with the Reading the Mind in the Eyes Test.
Timepoint [1] 301402 0
Pre single dose administration; between 45 and 90 minutes post single dose administration; and at 1 week for each treatment period.
Primary outcome [2] 301403 0
Participant’s perspective-taking as assessed by the carer version of the Interpersonal Reactivity Index.
Timepoint [2] 301403 0
Pre single dose administration and at 1 week for each treatment period.
Primary outcome [3] 303818 0
Participant’s empathic concern as assessed by the carer version of the Interpersonal Reactivity Index.
Timepoint [3] 303818 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [1] 332540 0
Speed and emotion recognition as assessed by the Facial Speed and Recognition Task.
Timepoint [1] 332540 0
Pre single dose administration; between 45 and 90 minutes post single dose administration; and at 1 week for each treatment period.
Secondary outcome [2] 332543 0
Emotion recognition as assessed using the Emotion Evaluation Test.
Timepoint [2] 332543 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [3] 335640 0
Emotion discrimination as assessed using the Emotion Discrimination Test.
Timepoint [3] 335640 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [4] 335641 0
Difference in patient-carer relationships as reported by the carer on the Intimate Bond Measure.
Timepoint [4] 335641 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [5] 335642 0
Difference in patient apathy as reported by the carer on the Apathy Evaluation Scale.
Timepoint [5] 335642 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [6] 335643 0
Difference in caregiver burden as reported by the Zarit Burden Interview.
Timepoint [6] 335643 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [7] 335644 0
Differences in the participant’s quality of life as reported by the WHO (Five) Well-Being Index.
Timepoint [7] 335644 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [8] 335645 0
Difference in the participant’s sleeping habits as reported by the carer on the HBA Sleep Questionnaire.
Timepoint [8] 335645 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [9] 335646 0
Difference in the participant’s behaviour as reported by the carer on the Socioemotional Dysfunction Scale.
Timepoint [9] 335646 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [10] 335647 0
Difference in the participant’s cognitive and behavioural changes as assessed by the Carer-Report Functional Decline Scale.
Timepoint [10] 335647 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [11] 335649 0
Difference in the carer’s mood as assessed by the 15-item Geriatric Depression Scale.
Timepoint [11] 335649 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [12] 335651 0
Difference in the participant’s behaviour (e.g., aggression, apathy, disinhibition, irritability) and mood (e.g. depression, dysphoria, anxiety, elation) as assessed by the Neuropsychiatric Inventory.
Timepoint [12] 335651 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [13] 335652 0
Differences in participant's neuropsychological status as measured by a neuropsychological test battery comprising the following domains: Memory (Hopkins Verbal Learning Test); Reaction Time (Trail Making, Part A); Executive Functioning (Trail Making Part B, Verbal Fluency, Stroop); and Working Memory (WAIS-III Digit Span).
Timepoint [13] 335652 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [14] 335653 0
Differences in the participant's blood levels of oxytocin
Timepoint [14] 335653 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [15] 336811 0
‘in-vivo’ brain changes associated with intranasal oxytocin administration via magnetic resonance spectroscopy in the first 15 randomised participants who are eligible and consent to undergo a brain MRI scan.
Timepoint [15] 336811 0
Following a 1 week intervention for each treatment period.
Secondary outcome [16] 340008 0
Differences in the carers' quality of life as reported by the WHO (Five) Well-Being Index.
Timepoint [16] 340008 0
Pre single dose administration and at 1 week for each treatment period.
Secondary outcome [17] 366524 0
To assess the feasibility of recruitment in order to inform progression to a definitive randomised controlled trial, that is: 1) Percentage (and 95% confidence intervals) of eligible patients who consent to study enrolment. Expected value greater than 50%. Our “stop -go” measures will be related to feasibility - > 50% - go to main trial, 30 – 50% – consider a modified trial design, <30% do not progress to main trial using this model.
Timepoint [17] 366524 0
Following trial closeout
Secondary outcome [18] 366525 0
To assess the acceptability of enrolment in order to inform progression to a definitive randomised controlled trial, that is: 1) Percentage (and 95% confidence intervals) of randomised participants who complete their final 1-week Follow-up (T5) assessment. 2) Percentage (and 95% confidence intervals) of randomised participants who are lost to follow up.
Timepoint [18] 366525 0
Following the final 1-week Follow-up (T5) assessment.
Secondary outcome [19] 366526 0
To assess trial medication adherence in order to inform progression to a definitive randomised controlled trial: 1) Percentage (and 95% confidence intervals) of randomised participants that adhere to greater than or equal to 70% (10/14 INOT doses) of the allocated treatment.
Timepoint [19] 366526 0
Following a 1 week intervention for each treatment period

Eligibility
Key inclusion criteria
To be eligible participants must:
1. 60 to 90 years of age
2. Have a diagnosis of mild AD, Vascular Dementia or mixed AD / Vascular Dementia
(MMSE > 21)
3. Have a carer who will be able to live with the participant during the study
Minimum age
60 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded if they:
1. Have prior history of psychiatric disorders (e.g. major depression, schizophrenia, bipolar disorder)
2. Have a score of =< 40 on the Benton Facial Recognition Test
3. Have a score on the 18-item Hamilton Depression Rating Scale greater than 16
4. Have been prescribed an anticholinesterase medication for less than three months or are experiencing side effects secondary to this class of medication.
5. Have been prescribed an antidepressant medication for less than one month or if they are experiencing side effects related to this medication or if the particular antidepressant is contraindicated with an INOT intervention
6. Currently prescribed any of the following classes of medications: non-anticholinesterase medications for dementia, antipsychotics, benzodiazepines, sedatives, and hypnotics
7. Have prior history of neurological disorder (e.g., head injury, stroke or transient ischemic attack, epilepsy)
8. Have a diagnosis of another neurodegenerative disease (e.g., Dementia with Lewy Bodies, Frontotemporal Dementia, Parkinson’ Disease Dementia)
9. Have an intellectual disability
10. Have a current history of substance abuse
11. Has a history of a myocardial infarction within the last two years or congestive heart failure
12. Current uncontrolled hypertension
13. Current bradycardia (rate < 50 beats per minute/bpm) or tachycardia (rate > 100 bpm)
14. Has a diagnosis of long QT syndrome
15. Current use of prostaglandins and their analogues
16. Current use of any anaesthetic (inhalation or caudal)
17. Known allergies to oxytocin or to preservatives in the nasal spray
18. Participants with severe nasal obstruction/blockage
19. Participants with severely compromised hepatic function
20. Participants with severely compromised renal function

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 "off-site" (Royal Prince Alfred Pharmacy, Sydney Camperdown, NSW) to the central administration site. Participants will be enrolled "on-site" at the central administration site (Brain and Mind Centre, University of Sydney, Camperdown, NSW).

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Prior to study enrolment, all participants will be provided with a sequential screening number. This screening number will identify the participant up until eligibility and enrolment is confirmed. Following enrolment, the participant will be allocated the next available unique randomisation ID. All randomisation IDs will be generated through randomisation software, using a random block size that is not available to staff who enrol participants. Regardless of treatment allocation (oxytocin or placebo), the first 15 randomised participants who are eligible and consent will be offered to undergo a brain MRI scan.
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
Intervention assignment
Crossover
Other design features
Men and women aged 60-90 years with a diagnosis of early Alzheimer's disease and/or Vascular dementia (MMSE > 21) will be referred from the Healthy Brain Ageing Clinic, at the Brain and Mind Centre. Once consent is obtained and eligibility is confirmed by a Geriatric medical practitioner along with the Trial Coordinator, the participant will be enrolled in the study.
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This study is a pilot study to determine an overall effect size to fund larger trials. Based on previous similar studies, it is estimated there will be >80% power to determine a medium to large effect size with this sample of 40 participants (and crossover design).

Repeated measures ANOVAs will be used to model change in all primary social cognition outcome variables and all secondary outcome variables over time as functions of treatment (oxytocin and placebo). All analyses will be two-tailed with an alpha of 0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7643 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment postcode(s) [1] 15550 0
2006 - The University Of Sydney
Recruitment postcode(s) [2] 15551 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 295870 0
Charities/Societies/Foundations
Name [1] 295870 0
The Judith Jane Mason & Harold Stannett Williams Memorial Foundation
Address [1] 295870 0
ANZ Trustees
Level 4, 100 Queen Street
Melbourne Vic 3000
Country [1] 295870 0
Australia
Funding source category [2] 295871 0
Charities/Societies/Foundations
Name [2] 295871 0
Alzheimer's Australia Dementia Research Foundation
Address [2] 295871 0
42 Macquarie St,
Barton ACT 2600
Country [2] 295871 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Brain and Mind Centre, University of Sydney
100 Mallett Street
Camperdown,
NSW, 2050
Country
Australia
Secondary sponsor category [1] 295621 0
None
Name [1] 295621 0
Address [1] 295621 0
Country [1] 295621 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297142 0
Research Ethics and Governance Office, Royal Prince Alfred Hospital
Ethics committee address [1] 297142 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital,
Camperdown, NSW, 2050
Ethics committee country [1] 297142 0
Australia
Date submitted for ethics approval [1] 297142 0
09/11/2016
Approval date [1] 297142 0
14/03/2017
Ethics approval number [1] 297142 0
X15-0255 & HREC/16/RPAH/638

Summary
Brief summary
People with dementia often experience difficulty in recognising the emotions of other people, such as fear, anger and sadness. This can impact upon relationships and social interactions thus causing distress for the individual living with dementia as well as for family members and friends. This study investigates whether a naturally occurring hormone in the body, oxytocin, can help people with Alzheimer's disease and/or Vascular dementia recognise the emotions of other people better. It is hypothesised that patients who receive the oxytocin nasal spray will demonstrate improved accuracy of emotion recognition, following a single dose and repeated administration over one week. Furthermore, it is also hypothesised carers of patients who receive the oxytocin nasal spray will report improved interactions and reduced caregiver burden.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73110 0
Prof Sharon Naismith
Address 73110 0
The Brain & Mind Centre
Healthy Brain Ageing Program,
94 Mallett St, Camperdown
The University of Sydney
NSW 2050 AUSTRALIA
Country 73110 0
Australia
Phone 73110 0
+61293510781
Fax 73110 0
+61293510551
Email 73110 0
sharon.naismith@sydney.edu.au
Contact person for public queries
Name 73111 0
Mr Johannes Michaelian
Address 73111 0
The Brain & Mind Centre
Healthy Brain Ageing Program,
94 Mallett St, Camperdown
The University of Sydney
NSW 2050 AUSTRALIA

Country 73111 0
Australia
Phone 73111 0
+61293510621
Fax 73111 0
+61293510551
Email 73111 0
johannes.michaelian@sydney.edu.au
Contact person for scientific queries
Name 73112 0
Mr Johannes Michaelian
Address 73112 0
The Brain & Mind Centre
Healthy Brain Ageing Program,
94 Mallett St, Camperdown
The University of Sydney
NSW 2050 AUSTRALIA
Country 73112 0
Australia
Phone 73112 0
+61293510621
Fax 73112 0
+61293510551
Email 73112 0
johannes.michaelian@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results