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Trial registered on ANZCTR


Registration number
ACTRN12621000926831
Ethics application status
Approved
Date submitted
20/04/2021
Date registered
15/07/2021
Date last updated
19/05/2023
Date data sharing statement initially provided
15/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
AustraLIan trial of GeNotype-guided pharmacothErapy for Depression (ALIGNED Study)
Scientific title
An Australian, Multicentre, Double-Blind, Randomised, Controlled Trial of Genotype-Guided versus Standard Psychotropic Therapy for Symptom Remission in Adults with Moderate-to-Severe Depression Initiating Pharmacotherapy
Secondary ID [1] 304009 0
None
Universal Trial Number (UTN)
Trial acronym
ALIGNED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 321630 0
Condition category
Condition code
Mental Health 319371 319371 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Materials used: a Treatment Guide will be prepared by the Treatment Guide Writing Group; the Treatment Guide will list recommended antidepressant medication(s) that are TGA approved/PBS-listed, chosen from current practice guidelines (Australian and New Zealand College of Psychiatrists’ Clinical Practice Guidelines for Major Depression, 2018 and the latest edition of Therapeutic Guidelines: Psychotropic (Version 8)) for participants based on their pharmacogenomic test results. Participants in the intervention group will be given an individualised Treatment Guide based on their pharmacogenomic results. The Treatment Guide may recommend a lower starting dose but with a therapeutic dose that falls within the TGA-recommended dosing range. It is unlikely that the individualised Treatment Guide will recommend a maintenance dose that deviates from the TGA-recommended dosing range, and under no circumstance will the Treatment Guide recommend a dose higher than the maximum TGA-recommended dose. Participants in the control group will be given a standard treatment plan that adheres to TGA-recommended doses based on current ANZ guidelines.

Procedure and activities: pharmacogenomic testing will be used to identify the most appropriate antidepressant medication(s) for participants. Participants will be provided with a kit to collect a buccal swab sample at home, which will be shipped to the pharmacogenomic testing laboratory by courier. A single pharmacogenomic test will take place from a single sample collected at baseline. Pharmacogenomic testing will occur 10-14 days prior to participants commencing treatment per their individualised Treatment Guide. The results of the pharmacogenomic testing will be provided to participants’ treating clinician. Participants will be encouraged to discuss their results with their treating clinician.

A Treatment Guide Writing Group will prepare individual Treatment Guides for participants based on their pharmacogenomic test results. The Treatment Guide Writing Group will comprise registered psychiatrists, a registered clinical geneticist, a general practitioner, psychiatry and clinical genetics registrars.

Intervention delivery: the Treatment Guide will be provided to the participant’s treating clinician e.g. GP, who will prescribe antidepressant therapy according to the recommendation(s) in the Treatment Guide.

Mode of intervention delivery: prescription of antidepressant therapy will be done by the participant’s treating clinician during a standard-of-care clinic visit.

Frequency of intervention: the intervention will be delivered once, within 7 days of day 0, following which, participants will be monitored by their treating clinician and depending on their response, the treating clinician has the discretion of deciding whether prescription changes are needed. If prescription changes are needed, the treating clinician is advised to follow the recommendations made in the Treatment Guide.

Unblinding will occur at the week 12 time point (after week 12 assessments have been completed). The results of the pharmacogenomic testing will be provided to participants’ treating clinician. Participants will be encouraged to discuss their results with their treating clinician.

The overall duration of the study is 24 weeks. Participants will also be followed by the study team at regular time points over 24 weeks.

Location where intervention occurs: the intervention occurs at the participant’s treating clinician’s clinic as part of routine standard-of-care visit.

Assessment of adherence to intervention: the antidepressant(s) prescribed to participants by their treating clinician (determined by participant self-report, review of PBS data) will be compared to those recommended by the Treatment Guide to assess clinician adherence to the intervention. Participant adherence to intervention will be assessed by validated adherence scales at regular time points.
Intervention code [1] 320320 0
Treatment: Other
Comparator / control treatment
Standard, guideline-informed (Australian and New Zealand College of Psychiatrists’ Clinical Practice Guidelines for Major Depression, 2018 and the latest edition of Therapeutic Guidelines: Psychotropic (Version 8)) antidepressant treatment guide.
Control group
Active

Outcomes
Primary outcome [1] 327228 0
The primary outcome is depression symptom remission at week 12, which assesses the absence or presence of symptoms associated with depression. Depression symptoms are assessed using the Montgomery and Åsperg Depression Rating Scale (MADRS).
Timepoint [1] 327228 0
Week 12
Secondary outcome [1] 394294 0
Response to antidepressants from baseline to week 12, which involves quantification of the degree of improvement in various symptoms associated with depression as assessed by a study personnel. Response to antidepressants is assessed using the Montgomery and Åsperg Depression Rating Scale (MADRS).
Timepoint [1] 394294 0
Baseline, Week 12
Secondary outcome [2] 394295 0
Response to antidepressants from baseline to week 12, which involves quantification of the degree of improvement in various symptoms associated with depression as self-reported by participants. Changes in depression symptoms are assessed using the 16-Item Quick Inventory of Depressive Symptomology – Self-Report (QIDS-SR) score.
Timepoint [2] 394295 0
Baseline, Week 12
Secondary outcome [3] 394296 0
Tolerability to antidepressant therapy, defined as the difference in Antidepressant Side Effect Checklist score between the pharmacogenomic (PG)-informed treatment arm and the standard treatment arm.
Timepoint [3] 394296 0
Week 12
Secondary outcome [4] 394297 0
Tolerability of antidepressant therapy, defined as discontinuation of antidepressant medication due to adverse effects. Tolerability will be assessed by participant self-report.
Timepoint [4] 394297 0
Week 12
Secondary outcome [5] 394298 0
Adherence to antidepressant therapy, defined as the difference in self-reported adherence to medication questionnaire score between the PG-informed treatment arm and the standard treatment arm. The validated adherence to medication questionnaire is the Three-Item Self-Report Measure for Medication Adherence.
Timepoint [5] 394298 0
Week 12

Eligibility
Key inclusion criteria
1. Aged between 18 and 70 years (inclusive)
2. Sufficiently fluent in English
3. Diagnosed with Major Depressive Disorder, either first-episode or relapsed, on the Mini-International Neuropsychiatric Interview Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria
4. A moderate to severe level of depression as rated on the Montgomery and Åsberg Depression Rating Scale (MADRS) with a score of > 19 at baseline
5. Person in whom antidepressants are indicated based on the current ANZ guideline but are yet to be initiated during current episode
6. Willing and able to provide informed consent
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Already taking an antidepressant or have not ceased antidepressant therapy at least 30 days before the screening visit
2. Significant suicidal risk (as determined during screening MADRS and DSM-5 MINI assessments)
3. Substance use disorder not in remission (other than nicotine or caffeine or mild alcohol use disorder) (as determined during screening DSM-5 MINI assessments)
4. Concurrent psychiatric diagnosis of bipolar disorder, or psychotic disorder (psychotic major depressive disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder), or cognitive disorders (intellectual impairment/dementia) (determined by participant medical history or during screening DSM-5 MINI assessment)
5. Current history of hepatic or renal failure confounding drug metabolism
6. Contraindication, including hypersensitivity (e.g. anaphylaxis), to SSRI, SNRI, mirtazapine and moclobemide.
7. Pregnant or breast feeding

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 using randomisation list.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
An intention-to-treat (ITT) approach will be used for efficacy analysis. A sample size of 776 participants will provide over 90% power at p=0.05 to detect a relative risk (RR) for remission of 1.4, which assumes a rate of remission of 30% in the control group and 42% in the intervention group and a dropout rate of 10%.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/10/2022
Actual
18/10/2022
Date of last participant enrolment
Anticipated
1/07/2025
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
776
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 308390 0
Government body
Name [1] 308390 0
National Health and Medical Research Council (NHMRC) Medical Research Future Fund (MRFF)
Country [1] 308390 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
The George Institute for Global Health
Level 5, 1 King St, Newtown, NSW 2042
Country
Australia
Secondary sponsor category [1] 309223 0
None
Name [1] 309223 0
Address [1] 309223 0
Country [1] 309223 0
Other collaborator category [1] 281750 0
University
Name [1] 281750 0
University of New South Wales
Address [1] 281750 0
Kensington, Sydney, NSW 2052
Country [1] 281750 0
Australia
Other collaborator category [2] 281751 0
University
Name [2] 281751 0
Australian National University
Address [2] 281751 0
Canberra, ACT 2600
Country [2] 281751 0
Australia
Other collaborator category [3] 281752 0
University
Name [3] 281752 0
Macquarie University
Address [3] 281752 0
Balaclava Rd, Macquarie Park NSW 2109
Country [3] 281752 0
Australia
Other collaborator category [4] 281754 0
University
Name [4] 281754 0
University of Sydney
Address [4] 281754 0
Camperdown NSW 2006
Country [4] 281754 0
Australia
Other collaborator category [5] 281755 0
University
Name [5] 281755 0
University of Western Australia
Address [5] 281755 0
35 Stirling Highway
Perth WA 6009
Country [5] 281755 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308354 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 308354 0
Ethics committee country [1] 308354 0
Australia
Date submitted for ethics approval [1] 308354 0
03/05/2021
Approval date [1] 308354 0
22/07/2021
Ethics approval number [1] 308354 0
2021/ETH00806

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

Contacts
Principal investigator
Name 110422 0
A/Prof Kathy Wu
Address 110422 0
St Vincent's Clinical Genomics
Translational Research Centre
97-105 Boundary Street
Darlinghurst NSW 2010
Country 110422 0
Australia
Phone 110422 0
+61 2 8382 4899
Fax 110422 0
Email 110422 0
[email protected]
Contact person for public queries
Name 110423 0
Niru Wijesuriya
Address 110423 0
The George Institute for Global Health
Level 5, 1 King St
Newtown, NSW 2042
Country 110423 0
Australia
Phone 110423 0
+61 2 8052 4300
Fax 110423 0
Email 110423 0
[email protected]
Contact person for scientific queries
Name 110424 0
Kathy Wu
Address 110424 0
St Vincent's Clinical Genomics
Translational Research Centre
97-105 Boundary Street
Darlinghurst NSW 2010
Country 110424 0
Australia
Phone 110424 0
+61 2 8052 4300
Fax 110424 0
Email 110424 0
[email protected]

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.