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Trial registered on ANZCTR


Registration number
ACTRN12618001807246
Ethics application status
Approved
Date submitted
30/10/2018
Date registered
6/11/2018
Date last updated
6/11/2018
Date data sharing statement initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of intranasal oxytocin on emotion processing and carer burden in individuals diagnosed with frontotemporal dementia
Scientific title
Effects of intranasal oxytocin on emotion processing in frontotemporal dementia
Secondary ID [1] 295558 0
Nil Known
Universal Trial Number (UTN)
U1111-1218-4356
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Frontotemporal Dementia 308829 0
Emotion Processing 308830 0
Condition category
Condition code
Neurological 307758 307758 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Twice-daily administration of 24IU Oxytocin Nasal Spray (generic).
Molecular Formula: C43H66N12O12S2
Molecular Weight: 1007.2
CAS Registry: 50-56-6

Dosage: 24IU administered twice a day (total dosage = 48IU)
Duration: 1 week
Mode: Intranasal
Formulation: A bulk oxytocin solution of 24 IU/50µL will be prepared by mixing oxytocin USP drug substance with a diluent. The diluent will consist of glycerol (2%), sorbitol (2%) benzyl alcohol (0.9%) and water for irrigation.

Treatment Regime (3-4 weeks total duration)
The cross-over study design will implement two arms with alternating intervention regimes which participants will be randomly assigned to.
Arm 1: 24 IU Oxytocin administered for 1 week, followed by a 1 week washout period and then placebo administered for 1 week
Arm 2: Placebo administered for 1 week, followed by a 1 week washout period and then 24 IU Oxytocin administered for 1 week
Intervention period: one week
Washout period: one week

Research Visits
Visit 0 + 1 (time points 0 and 1 - Day 1): Informed consent session, enrolment and medical assessment to confirm eligibility. Primary and secondary outcome measures assessed prior to single dose administration for baseline. Single-dose administration of first intervention followed by assessment of relevant primary and secondary outcome measures. Intranasal bottle and instructions provided for first intervention period.

Visit 2 (time point 2 - Day 7): Post intervention period follow-up. Monitoring and assessment of primary and secondary outcomes measures. Collection of intranasal bottle from first intervention period.

Visit 3 (time point 3 and 4 - Day 14): Post washout period, primary and secondary outcome measures assessed for baseline prior to single-dose administration of second intervention. Single-dose administration of alternate intervention followed by assessment of relevant primary and secondary outcome measures. Intranasal bottle and instructions repeated for second intervention period.

Visit 4 (time point 5 - Day 21): Post intervention period follow-up. Monitoring and assessment of primary and secondary outcomes measures. Collection of intranasal bottle from second intervention period.

Note: Follow-up calls will be made between 3-5 days into the intervention periods. Final follow-up phone calls will be made 3-5 days after the final visit.

Interventional adherence and participant compliance will be monitored using a side effect monitoring diary that the participant and/or carer will maintain throughout the intervention period. Research staff will further monitor compliance during clinic visits using monitoring logs.
Intervention code [1] 301857 0
Treatment: Drugs
Comparator / control treatment
Placebo-controlled (Saline Mist Nasal Spray)

Group: Active control (crossover)
Administration: Nasal Spray
Saline Mist formulation: Saline mist will only contain the diluent consisting of glycerol (2%), sorbitol (2%) benzyl alcohol (0.9%) and water for irrigation.
Duration: 1 week
Control group
Active

Outcomes
Primary outcome [1] 307004 0
Performance on The Awareness of Social Inference Test (TASIT) following placebo and active drug intervention phases in comparison to baseline. The TASIT is a video-based assessment of social cognition and basic emotion recognition.
Timepoint [1] 307004 0
Pre single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)
Primary outcome [2] 307005 0
Difference in scoring on the Cambridge Behavioural Inventory (CBI) following placebo and active drug intervention phases in comparison to baseline. The CBI is an informant-based questionnaire used to differentiate neurodegenerative syndromes across ten behavioural domains such as memory, mood, eating habits, sleep etc.
Timepoint [2] 307005 0
Pre single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)
Secondary outcome [1] 350331 0
Performance on the Facial Speed and Recognition Task following placebo and active drug intervention phases in comparison to baseline. This task assesses the emotion recognition and response capabilities of participants using photographic stimuli on a screen.
Timepoint [1] 350331 0
Post single-dose administration of intervention (Visit 1 and Visit 3) and one week post-intervention (Visit 2 and Visit 4)
Secondary outcome [2] 350332 0
Performance on standard neuropsychological assessment of cognition using the Addenbrooke's Cognitive Examination-Third edition (ACE-III). This test assesses the participant's performance on commonly assessed cognitive domains such as orientation, attention, memory, verbal ability and language comprehension.
Timepoint [2] 350332 0
Pre-intervention administration (Visit 0), One-week post-intervention (Visit 2 and Visit 4)
Secondary outcome [3] 352022 0
Difference in performance on the Facial Affect and Identity Test (assessing emotion perception) following placebo and active drug intervention phases in comparison to baseline.
Timepoint [3] 352022 0
Pre single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)
Secondary outcome [4] 352024 0
Difference in blood levels of oxytocin following one week of intervention with oxytocin and placebo in comparison to baseline.
Timepoint [4] 352024 0
Blood samples will be collected at Visit 0 (pre single-dose administration 1), Visit 2 (1-week follow-up 1), Visit 3 (pre single-dose administration 2) and Visit 4 (1-week follow-up 2).
Secondary outcome [5] 353600 0
Performance on standard neuropsychological assessment of cognition using the Trail Making Test.
Timepoint [5] 353600 0
Pre-intervention administration (Visit 0), One-week post-intervention (Visit 2 and Visit 4)
Secondary outcome [6] 353601 0
Performance on standard neuropsychological assessment of cognition using the Digit Span Memory Test.
Timepoint [6] 353601 0
Pre-intervention administration (Visit 0), One-week post-intervention (Visit 2 and Visit 4)
Secondary outcome [7] 353602 0
Performance on standard neuropsychological assessment of cognition using the Hayling Sentence Completion Test.
Timepoint [7] 353602 0
Pre-intervention administration (Visit 0), One-week post-intervention (Visit 2 and Visit 4)
Secondary outcome [8] 353604 0
Performance on standard neuropsychological assessment of cognition using the Rey Auditory Verbal Learning Test.
Timepoint [8] 353604 0
Pre-intervention administration (Visit 0), One-week post-intervention (Visit 2 and Visit 4)
Secondary outcome [9] 353606 0
Difference in carer-reported levels of carer burden measured by the Zarit Burden Inventory following oxytocin and placebo intervention in comparison to baseline.
Timepoint [9] 353606 0
Pre single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)
Secondary outcome [10] 353607 0
Difference in carer-reported levels of relationship quality measured by the Intimate Bond Measure following oxytocin and placebo intervention in comparison to baseline.
Timepoint [10] 353607 0
Pre single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)
Secondary outcome [11] 353608 0
Difference in carer-reported levels of empathy measured by the Interpersonal Reactivity Index following oxytocin and placebo intervention in comparison to baseline.
Timepoint [11] 353608 0
Pre-single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)
Secondary outcome [12] 353609 0
Difference in carer-reported levels of behavioural and neuropsychiatric symptoms measured by the Neuropsychiatry Inventory following oxytocin and placebo intervention in comparison to baseline.
Timepoint [12] 353609 0
Pre-single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)
Secondary outcome [13] 353610 0
Difference in carer-reported levels of apathy measured by the Dimensional Apathy Scale following oxytocin and placebo intervention in comparison to baseline.
Timepoint [13] 353610 0
Pre-single-dose administration (Visit 0), One week post-intervention (Visit 2 and Visit 4)

Eligibility
Key inclusion criteria
1. Be within 40 to 75 years of age
2. Have a diagnosis of behavioural variant frontotemporal dementia, semantic dementia, or progressive non-fluent aphasia
3. Have a carer who will be able to live with the participant during the study
Minimum age
40 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severely compromised cardiac, hepatic or renal function
2. Severe nasal obstruction/blockage
3. Sensitivity to preservatives (in particular benzyl alcohol 0.9%), which are present in the nasal spray formulation
4. Upcoming surgery, due to concerns of interactions with other medications
5. Prior history of psychiatric disorders (e.g. major depression, schizophrenia, bipolar disorder)
6. Prescribed an anticholinesterase medication for less than three months or are experiencing side effects secondary to this class of medication.
7. Have prior history of neurological disorder other than dementia (e.g., head injury, stroke or transient ischemic attack, epilepsy)
8. Have a diagnosis of another neurodegenerative disease (e.g., Dementia with Lewy Bodies, Alzheimer’s Disease, Parkinson’ Disease)
9. Have an intellectual disability
10. Have a current history of substance abuse

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)
Central randomisation by computer provided to the drug dispensary off-site by an unblinded member of the team who was not involved in subject recruitment or testing.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculation
The total sample size is 40. The crossover design maximizes power as it obtains both treatment and placebo data for the full sample. Our sample size calculation of N=40 allows for 10% attrition, and assumes a medium effect size.

Data analysis
Repeated measures ANOVAs will be utilised to test for differences between oxytocin and placebo across cognitive assessments and blood samples.

Descriptive statistics will include number of participants (N), mean, standard deviation, minimum, maximum and if a non- normal distribution, the median and first/third quartiles will be reported.

Recruitment
Recruitment status
Not yet 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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 12203 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment postcode(s) [1] 24377 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 300135 0
Government body
Name [1] 300135 0
National Health and Medical Research Council
Address [1] 300135 0
Postal address
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Canberra Office - Physical address
16 Marcus Clarke St
Canberra ACT 2601
Country [1] 300135 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
Camperdown NSW 2006 Australia
Country
Australia
Secondary sponsor category [1] 300244 0
None
Name [1] 300244 0
Address [1] 300244 0
Country [1] 300244 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300970 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 300970 0
Margaret Telfer Building (K07)
University of Sydney
Camperdown NSW 2006
Ethics committee country [1] 300970 0
Australia
Date submitted for ethics approval [1] 300970 0
28/11/2017
Approval date [1] 300970 0
27/04/2018
Ethics approval number [1] 300970 0

Summary
Brief summary
This trial aims to determine the effects of short-term intranasal oxytocin intervention on emotional processing in individuals diagnosed with Frontotemporal Dementia . We further wish to evaluate whether administration of oxytocin has an effect on carer-burden using standardised questionnaires to capture changes in patient-carer relationships.

Who is it for?
Patients between the ages of 40 to 75 years, who have been diagnosed with behavioural variant frontotemporal dementia, semantic dementia or progressive non-fluent aphasia, and have a carer who will be able to live with them for the duration of the study are eligible to participate.

Study details
Patients who have previously been recruited by the Frontier Research Clinic for the 'Clinical Assessment for Ageing and Neurodegeneration Research' study will be contacted to participate in this four-week clinical trial using oxytocin nasal spray.

Patients will undergo clinical and neuropsychological assessments at their initial visit, followed by assessments of emotion, cognition, carer-burden and blood sampling at further visits. Patients will be randomised to receive either placebo or oxytocin for one-week, then be off any intervention for one week followed by the counter-intervention for a one-week period. Experimental tasks and clinical assessments will be performed at the Brain and Mind Centre on appropriate visit days and study compliance will be monitored using a drug diary and help from the caregiver.
Trial website
https://sydney.edu.au/brain-mind/patient-services/ageing-and-neurodegeneration-clinics/forefront-ageing-and-neurodegeneration-clinics/forefront-frontier-clinic-frontotemporal-dementia.html

Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85462 0
Prof Olivier Piguet
Address 85462 0
Brain and Mind Centre, The University of Sydney
Level 3, 100 Mallett Street, Camperdown 2050 NSW
Country 85462 0
Australia
Phone 85462 0
+61 2 9114 4144
Fax 85462 0
Email 85462 0
olivier.piguet@sydney.edu.au
Contact person for public queries
Name 85463 0
Prof Olivier Piguet
Address 85463 0
Brain and Mind Centre, The University of Sydney
Level 3, 100 Mallett Street, Camperdown 2050 NSW
Country 85463 0
Australia
Phone 85463 0
+61 2 9114 4144
Fax 85463 0
Email 85463 0
olivier.piguet@sydney.edu.au
Contact person for scientific queries
Name 85464 0
Prof Olivier Piguet
Address 85464 0
Brain and Mind Centre, The University of Sydney
Level 3, 100 Mallett Street, Camperdown 2050 NSW
Country 85464 0
Australia
Phone 85464 0
+61 2 9114 4144
Fax 85464 0
Email 85464 0
olivier.piguet@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