Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000610730
Ethics application status
Approved
Date submitted
18/03/2022
Date registered
22/04/2022
Date last updated
28/09/2023
Date data sharing statement initially provided
22/04/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Recovery Training of Emotion and Cognition with Vortioxetine for Depression (RECOVER-D) Study
Scientific title
Evaluating the feasibility and acceptability of a combined treatment for depression using a personalised psychosocial intervention and Vortioxetine in older adults.
Secondary ID [1] 306706 0
Nil
Universal Trial Number (UTN)
Trial acronym
RECOVER-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 325676 0
Condition category
Condition code
Mental Health 323022 323022 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomised to have the psychosocial intervention program will receive a personalised treatment stream of the psychosocial training intervention program that is tailored to address their weaknesses. The psychological treatment will target three domains of psychosocial functioning, which when impaired, appear to underlie psychosocial dysfunction in depression. These domains include cognition (e.g. attention, memory), emotion processing (e.g. pessimism), and social cognition (e.g. interpreting social situations). The current treatment will target functioning in these domains with repeated training tasks, following the rationale that therapeutic benefits will arise with psychosocial functioning. The one-on-one intervention will be conducted remotely online using a videoconferencing platform (Zoom) and delivered by trained researchers with a background in psychology. The intervention will have 8 sessions across 8 weeks with 1 session per week. Each session will be between 1 hour and 1.5 hours long. Adherence of the psychological intervention will be monitored through participants attendance of the weekly sessions.


Personalised interventions will be tailored to address participants’ weakest domains. Baseline tests will determine weakest area of functioning by evaluating participants’ performance with the THINC-it tool (cognition), verbal fluency task (cognition), the PANAS (emotion) and the WAIS-IV Social Cognition Test (social cognition). Significant weakness in these tests will be defined as performance at least 0.5 standard deviations below the norm.
On the basis of individual weaknesses, participants allocated to personalised treatment will be delivered one of four potential treatment streams; (1) high cognition treatment, (2) high emotion treatment, (3) high social cognition treatment, and (4) broad impairment treatment. Participants will be allocated to streams 1, 2 or 3 if their greatest weakness is primarily represented in one of the 3 baseline domains. Examples of training tasks include Emotion word brainstorming, Backwards digit span
Ray verbal learning Test, and go/ no go task.

Assessments will be completed at the baseline (week 1 of the intervention), halfway through the intervention (week 4) and at the conclusion of the intervention. These assessments will occur online through Zoom and be 1 hour in duration. In the assessments participants we will be asked a series of questions and complete measures that are designed to monitor/measure participants mood, depressive symptoms, anxiety, and functioning.

These participants will also receive the same antidepressant medication (Vortioxetine) given to the control group. Vortioxetine is recommended for use in adults with recommended doses for adults under 65 years of age being 10mg, taken orally once a day. For adults 65 years and older, a starting dose of 5mg once daily is recommended. These doses may be increased to 20mg per day or decreased to 5mg per day at the discretion of the psychiatrist. The administration of Vortioxetine will be monitored through the participant having telehealth visits with one of the psychiatrists working on the study. These mental health reviews with the psychiatrist will occur before the participant takes the Vortioxetine (in week 1 of the intervention) and week 3, week 5 and week 7 of the intervention. Blood tests will also be used to monitor participants sodium levels and will be before the participant begins taking Vortioxetine and then again two weeks after the participant firsts starts the medication. Additional blood tests will be administered if the participants dosage of Vortioxetine is increased by the psychiatrist. Participants can complete the blood tests at their local pathology centre or at Royal Melbourne Hospital pathology centre. Adherence to medication will be monitored through participants completing a medication diary and discussions with the psychiatrist during the mental health reviews. Vortioxetine administration will occur over the course of intervention (8 weeks). It takes 2-6 weeks to see the potential benefits of the Vortioxetine in the participant. As an extension phase of this study, a 6-month supply of the medication will be available to participants (free of charge) once the study has ended. This will be dispensed in an initial 3 month supply with a further 3 month supply accessible following a review of the participant by their General Practitioner. After this point, the participant will have the choice to continue the Vortioxetine, incurring the full cost of the medication, or switch to another anti-depressant that is supplied under the pharmaceutical benefits scheme.

Intervention code [1] 323151 0
Behaviour
Intervention code [2] 323164 0
Treatment: Drugs
Intervention code [3] 323209 0
Treatment: Other
Comparator / control treatment
Participants randomised to the control group will receive a standard/non-tailored treatment version of the computerised psychosocial training program. The session duration, delivery and mode will be the same as the intervention group. Participants in the control group will receive one-on-one intervention will be conducted remotely online using a videoconferencing platform (Zoom) and delivered by trained researchers with a background in psychology. The intervention will have 8 sessions across 8 weeks with 1 session per week. Each session will be between 1 hour and 1.5 hours long. Adherence to the psychological intervention will be monitored through participants' attendance at the weekly sessions. All participants, regardless of group assignment, will receive the same antidepressant medication (Vortioxetine). Participants in the control will also complete assessments, receive vortioxetine dosing adjustments, and receive mental health review sessions in a similar manner to the intervention group.
Control group
Active

Outcomes
Primary outcome [1] 330804 0
The primary outcome will be a composite fasibility measure, tracked by members of the research team, from initial recruitment to week 8 (end of intervention) of the psychosocial treatment. Based on Moore, Carter, Nietert, and Stewart (2011), indices will include;
• The proportion of those screened as eligible who subsequently enrol in the study. This will be assessed by tracking the number of screened eligible participants compared to the number of participants who enrol in the study by auditing the screening and enrolment logs.
• The treatment-specific retention rates. this will be assessed by the proportion of participants enrolled in both interventions who complete the intervention.
• The rates of adherence to the protocol for each intervention. This will be assessed by using checklists.
• The proportion of scheduled visits that are completed. This will be assessed by using session attendance checklists.
• The proportion of participants that completed all assessments. This will be assessed by using assessment checklists.
• The proportion of participants that gave the required amount of blood. This will be assessed through checklists.
Timepoint [1] 330804 0
As the primary outcome is a composite measure, the tracking of the outcome will occur throughout the intervention, beginning in the recruitment stage and concluding at the end of the study (week 8).
Primary outcome [2] 331144 0
Measures of acceptability will be based on the theoretical framework proposed by Sekhon, Cartwright, and Francis (2017), and will include components of subjective participant experience during the study. A qualitative questionnaire will gauge participants’ subjective experience of the study intervention. This questionnaire will seek feedback about participants’ attitudes to the intervention, the perceived burden or effort of the intervention, their perception of the effectiveness of the intervention, and any barriers such as costs of participating. The participant’s confidence in their own ability to engage with the training sessions will also be assessed. Participants who withdraw from the study early will also be sent this survey.
Timepoint [2] 331144 0
After the participant has concluded participation in the study.
Secondary outcome [1] 407613 0
The key secondary outcome measure (psychosocial functioning) will be pre/post-change on the Functioning Assessment Short Test (FAST; Rosa et al, 2007), a 24-item, validated measure of functioning with high internal consistency (r = .90).
Timepoint [1] 407613 0
Assessed at baseline assessment (at time of intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [2] 407616 0
Depression severity, will be measured by the Montgomery Asberg Depression Rating Scale (MADRS) (Svanborg & Asberg, 2001).
Timepoint [2] 407616 0
Assessed at screening assessment (2 weeks prior to intervention commencement) baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [3] 407617 0
Perceived resilience, as measured by “The Resilience Scale” (Wagnild & Young, 1993), which has shown high internal consistency and concurrent validity.
Timepoint [3] 407617 0
Assessed at baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [4] 407618 0
Functional disability in daily life, as measured by the Sheehan Disability Scale (Leon et.al., 1997), which has high internal consistency and concurrent validity, with high scores indicative of mental health disorders.
Timepoint [4] 407618 0
Assessed at baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [5] 407619 0
Self-reported cognitive problems such as everyday slips of memory and attention will be evaluated with the Cognitive Failures Questionnaire (CFQ), which gauges the frequency of cognitive failures experienced in the past 6 months (Larson et.al., 1997).
Timepoint [5] 407619 0
Assessed at baseline assessment (at time of intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [6] 407620 0
Participants’ emotional state, as measured by the Positive and Negative Affect Schedule (PANAS), which has well-supported psychometric properties, including high internal consistency and convergent and discriminant validity (Crawford et al, 2004).
Timepoint [6] 407620 0
Assessed at baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [7] 407621 0
Cognitive functioning will be assessed with the THINC-it tool, a digitally administered screening instrument for cognitive impairment in depression. The THINC-it involves four objective tests of cognitive performance, including choice reaction time, a 1-back memory task, the Trail Making Test Part B and digit symbol substitution. The THINC-it also includes a 5-item component of the self-reported perceived deficit questionnaire, as an indication of retrospective cognitive dysfunction (Kinsinger et al, 2010).
Timepoint [7] 407621 0
Assessed at baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [8] 407622 0
The Weschler Adult Intelligence Scale Advanced Clinical Solutions Social Cognition Test (WAIS-IV-ACS) will be used to assess participants’ social cognition. The test involves three tasks designed to identify social cognitive impairment: Affect Naming, Prosody-Face Matching, and Prosody-Pair Matching.
Timepoint [8] 407622 0
Assessed at baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [9] 407623 0
Verbal functioning will be assessed with a verbal fluency task (Tombaugh, Kozak, & Rees, 1999).
Timepoint [9] 407623 0
Assessed at baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [10] 407624 0
Blood samples will be taken to monitor sodium levels for hyponatraemia, a potential side effect of Vortioxetine.
Timepoint [10] 407624 0
Blood tests will occur through the intervention including at the commencement of the intervention, 2 weeks post-intervention commencement. If the dosage of Vortioxetine has increased by a study doctor 4 weeks post-intervention commencement or 6 weeks post-intervention commencement, then additional blood tests to monitor sodium levels would be required 5 weeks post-intervention commencement and/or 7 weeks post-intervention commencement.
Secondary outcome [11] 407955 0
The Structured Interview Guide of the Hamilton Anxiety and Depression Scale (SIGH-AD). The SIGH–AD combines the Hamilton Depression Scale (HAM-D, 17 items) and the Hamilton Anxiety Scale (HAM-A, 14 items) (Williams, 1988). The SIGH-AD will be used to measure depression severity
Timepoint [11] 407955 0
Assessed at screening assessment (2 weeks prior to intervention commencement) baseline assessment (at time of intervention commencement), Mid-RCT assessment (4 weeks post-intervention commencement) and End-RCT Assessment (8 weeks post-intervention commencement).
Secondary outcome [12] 407959 0
Participants may also choose to have blood samples taken for genetic biomarker analysis.
Timepoint [12] 407959 0
The genetic blood test can happen at any timepoint that a participant is undertaking a sodium blood test during the study.

Eligibility
Key inclusion criteria
• Capacity to provide informed consent.
• Aged between 50 – 75 years of age.
• Able to see and hear, with or without sensory aids (e.g. glasses or hearing aids).
• Has adequate English skills to participate.
• Able to read and write.
• Has a Medicare card and a regular General Practitioner.
• Consents to the study team contacting their General Practitioner.
• Consent to take Vortioxetine during the study.
• Participants must not currently be taking anti-depressant medication.
• Current moderate depressive symptoms as confirmed by the Mini International Neuropsychiatric Interview (MINI).
• Depression symptom severity demonstrated as clinically significant (scores equaling or greater than 15) according to the Structured Interview Guide of the Hamilton Anxiety and Depression Scale (SIGH-AD).
• Depression symptom severity demonstrated as mild-moderate (16-19), or moderate (20-35) according the Montgomery Asberg Depression Rating Scale (MADRS) (Svanborg & Asberg, 2001).
• Reported duration of the current major depressive episode is at least 3 months.
• Participant has either been told or self-reports they are currently experiencing depressive symptoms.
• Participants must be willing and able to complete digital treatment tasks presented on a computer.
• Participants must have access to the internet and a computer/laptop in a private space.
• Study participant is willing to give blood samples during the study (at screening and week 2,as well as following any Vortioxetine dosage changes).
Minimum age
50 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Living in residential aged care (e.g. hostel or nursing home).
• Current alcohol and/or substance use disorder (DSM-5).
• Presence of a co-morbid psychiatric disorder other than mild to moderate depression that is a focus of clinical concern as confirmed by the MINI (e.g. schizophrenia or bipolar disorder).
• Depression symptom severity demonstrated as severe (36-60) according the Montgomery Asberg Depression Rating Scale (MADRS).
• People currently on antidepressant medication (except for Vortioxetine).
• People who are pregnant, trying to get pregnant or breast-feeding.
• People with active suicidality or a history of suicide attempt(s) within the past 2 years.
• Brain injury, neurological condition or impairment which could affect cognitive function (e.g. neurodevelopmental disorders, neurodegenerative disease, dementia).
• People currently taking medications approved for and/or employed off-label for cognitive dysfunction (e.g. psychostimulants).
• People currently taking any medication for a general medical disorder that in the opinion of the investigator may affect cognitive function (e.g. corticosteroids, beta-blockers).
• People currently on regular prescribed (i.e. not “as needed” or PRN) antipsychotic or benzodiazepine medication.
• People currently participating in a research drug trial.
• Physical, cognitive or language impairment(s) of some severity as to adversely affect data derived from the THINC-It tool.
• People who have received electroconvulsive therapy within the last 6 months (they may be invited to call back when 6 months have elapsed).
• A history of unsuccessful Vortioxetine use and known allergies to Vortioxetine.

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)
participants will not be randomly assigned to a group until after eligibility has been determined. Additionally, the researcher who assesses eligibility and the researcher randomising participants are different individuals.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A sequence of random numbers will be generated by computer for allocation to groups; this file will be stored in the password-protected research drive at the University of Melbourne, to be accessed only by research staff not directly involved in the study. Group assignment will occur after initial screening and eligibility for inclusion in the study is confirmed. Participants will be aware that they will be randomly allocated to one of the two groups (control or intervention), however they will be blind to their allocation until after the study is complete. Allocation to groups will be concealed from research staff involved in assessments throughout the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
In addition to reporting descriptive statistics for each continuous outcome measure, we will calculate the standardised mean difference effect size and its variance at post-intervention. We will use the recommended method of Morris and DeShon (2002) for within-group changes from pre-intervention to week 8 of the study and Hedge’s g for between-group differences at week 8 of the study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
4/03/2022
Date of last participant enrolment
Anticipated
30/06/2024
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 21989 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 21990 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment postcode(s) [1] 37091 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 311036 0
Hospital
Name [1] 311036 0
The Royal Melbourne Hospital Foundation
Country [1] 311036 0
Australia
Funding source category [2] 311050 0
University
Name [2] 311050 0
The University of Melbourne
Country [2] 311050 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
300 Grattan St, Parkville VIC 3050
Country
Australia
Secondary sponsor category [1] 312381 0
None
Name [1] 312381 0
Address [1] 312381 0
Country [1] 312381 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310584 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 310584 0
Ethics committee country [1] 310584 0
Australia
Date submitted for ethics approval [1] 310584 0
19/10/2019
Approval date [1] 310584 0
12/03/2020
Ethics approval number [1] 310584 0
MHREC 2019.252

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

Contacts
Principal investigator
Name 118166 0
Prof Nicola Lautenschlager
Address 118166 0
Royal Melbourne Hospital, Royal Park Campus, Ground floor, Building 5, 34-54 Poplar Rd
Parkville, Victoria 3052
Country 118166 0
Australia
Phone 118166 0
+61 383872326
Fax 118166 0
Email 118166 0
nicolatl@unimelb.edu.au
Contact person for public queries
Name 118167 0
Luella Mangeean
Address 118167 0
University of Melbourne
Academic Unit for Psychiatry of Older Age
151 Barry st, Carlton, Victoria, 3053
Country 118167 0
Australia
Phone 118167 0
+61 3 8344 1879
Fax 118167 0
Email 118167 0
luella.mageean@unimelb.edu.au
Contact person for scientific queries
Name 118168 0
Alissa Westphal
Address 118168 0
Royal Melbourne Hospital, Royal Park Campus, Ground floor, Building 5, 34-54 Poplar Rd
Parkville, Victoria 3052
Country 118168 0
Australia
Phone 118168 0
+61 451 017 294
Fax 118168 0
Email 118168 0
alissaw@unimelb.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 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.