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Trial registered on ANZCTR


Registration number
ACTRN12622000014752
Ethics application status
Approved
Date submitted
22/11/2021
Date registered
11/01/2022
Date last updated
15/04/2024
Date data sharing statement initially provided
11/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
GLAD Study: Genetics Linked to Anti-Depressants in Adults with Treatment Resistant Depression
Scientific title
An Australian Double-Blind Randomised Controlled Trial of Genotype-guided versus Standard Psychotropic Therapy for Symptom Remission in Adults with Treatment Resistant Depression
Secondary ID [1] 305313 0
Nil known
Universal Trial Number (UTN)
Trial acronym
GLAD Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 323631 0
Condition category
Condition code
Mental Health 321164 321164 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After informed consent, a single DNA sample using a buccal swab kit will be collected from all participants for pharmacogenomic (PG) testing at the Screening Visit.
For participants randomised to the intervention arm, the treatment plan for their antidepressants will be informed by the participant’s PG report - a recommendation for antidepressant prescribing guided by the participants' pharmacogenomic profile in line with TGA recommended doses. The recommendations about antidepressant class and dose are based on Clinical Pharmacogenetics Implementation Consortium (CPIC) and Royal Dutch Pharmacogenetics Working Group (DPWG) international guidelines.

All participants will commence treatment within 4 weeks after the Screening visit.
Participants will be reviewed at 2, 4 and 12 weeks after treatment initiation (Baseline visit).
Participant adherence to antidepressant treatment will be reviewed by the Investigators as per standard of care. In addition the Medication Adherence Report Scale (MARS-5) will be performed.

Both groups will be recommended medications that follows current TGA guidelines.
Intervention code [1] 321726 0
Treatment: Other
Comparator / control treatment
Standard treatment arm: The treatment plan for their antidepressants will follow current TGA guidelines but will not be informed by participant’s PG results.
Control group
Active

Outcomes
Primary outcome [1] 329128 0
The primary outcome is remission of depressive symptoms defined as change in depressive symptom score measured by Montgomery and Åsperg Depression Rating Scale (MADRS)
Timepoint [1] 329128 0
Baseline, Week 4, 12 (primary endpoint), 24 from Randomisation.
Secondary outcome [1] 401561 0
Response to antidepressants, defined as > 50% decrease in MADRS scores assessed using the Montgomery and Åsperg Depression Rating Scale
Timepoint [1] 401561 0
Baseline, Week 4, 12, 24 from Randomisation
Secondary outcome [2] 401562 0
Changes in self-reported depression symptoms as assessed using the 16-Item Quick Inventory of Depressive Symptomology – Self-Report (QIDS-SR)
Timepoint [2] 401562 0
Baseline, Week 4, 12, 24 from Randomisation.
Secondary outcome [3] 403258 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] 403258 0
Baseline, Week 4, 12 from Randomisation.

Eligibility
Key inclusion criteria
- Age 18 - 70 years
- Sufficiently fluent in English
- Diagnosed with MDD, either first-episode or relapsed, on Mini International Neuropsychiatric Interview (M.I.N.I.) 7.0.2 for DMS-5 criteria
- Montgomery and Asberg Depression Rating Scale (MADRS) score of greater than or equal to 20 at Screening and Baseline
- Failure of greater than or equal to 2 prior adequate trial of evidenced-based treatments in the current MDD episode
- 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
- Significant suicidal risk based on MADRS and/or M.I.N.I. 7.0.2 for DMS-5 criteria
- Substance use disorder not in remission (other than nicotine or caffeine) (as determined during screening DSM5 assessments)
- Concurrent psychiatric diagnosis of bipolar disorder, or psychotic disorder (psychotic MDD, schizophrenia, schizoaffective disorder, schizophreniform disorder), or cognitive disorders (intellectual impairment/dementia) (determined by participant medical history or during screening DSM-5 MINI assessment)
- Current history of significant hepatic or renal disease affecting drug metabolism.
- Pregnant or breast-feeding women

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)
Sealed opaque envelopes
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 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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2023
Actual
20/02/2024
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 309680 0
Commercial sector/Industry
Name [1] 309680 0
HBF Health Limited
Country [1] 309680 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
35 Stirling Hwy, Crawley, WA, 6009
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 310848 0
None
Name [1] 310848 0
Address [1] 310848 0
Country [1] 310848 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309447 0
The University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 309447 0
35 Stirling Hwy, Crawley WA 6009
Ethics committee country [1] 309447 0
Australia
Date submitted for ethics approval [1] 309447 0
16/09/2021
Approval date [1] 309447 0
22/10/2021
Ethics approval number [1] 309447 0

Summary
Brief summary
An Australian Double-Blind Randomised Controlled Trial of Genotype-guided versus Standard Psychotropic Therapy in People with Treatment Resistant Depression.

The study intervention consists of a pharmacogenomic (PG) test with resulting recommendations for which antidepressants may work better for that participant.
Eligible participants will be randomised to one of two arms.
1. PG-informed treatment arm: The treatment plan for their antidepressants will be informed by participant’s PG results.
2. Standard treatment arm: The treatment plan for their antidepressants will follow current treatment guidelines but will not be informed by participant’s PG results.
Both groups will be recommended medications that follows current treatment guidelines for moderate to severe treatment resistant depression.
To test the hypothesis that pharmacogenomic-guided treatment compared to standard treatment improves clinical outcomes in treatment-resistant MDD

Study Procedures
Pharmacogenetic testing
PG-informed or standard care antidepressant treatment
Clinical outcome assessments and questionnaires at baseline, and week 2, 4, 12 and 24
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114194 0
Prof Sean Hood
Address 114194 0
The University of Western Australia
35 Stirling Hwy, Crawley, WA, 6009
Country 114194 0
Australia
Phone 114194 0
+61 8 6151 1178
Fax 114194 0
Email 114194 0
sean.hood@uwa.edu.au
Contact person for public queries
Name 114195 0
Dr Carl Holm
Address 114195 0
The University of Western Australia
35 Stirling Hwy, Crawley, WA, 6009
Country 114195 0
Australia
Phone 114195 0
+61 8 6151 1178
Fax 114195 0
Email 114195 0
carl.holm@uwa.edu.au
Contact person for scientific queries
Name 114196 0
Dr carl.holm@uwa.edu.au
Address 114196 0
The University of Western Australia
35 Stirling Hwy, Crawley, WA, 6009
Country 114196 0
Australia
Phone 114196 0
+61 8 6151 1178
Fax 114196 0
Email 114196 0
carl.holm@uwa.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.