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Trial registered on ANZCTR


Registration number
ACTRN12621001374853
Ethics application status
Approved
Date submitted
31/08/2021
Date registered
11/10/2021
Date last updated
3/11/2024
Date data sharing statement initially provided
11/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacogenetics for Severe Mood Disorders: A Randomised Controlled Trial
Scientific title
The effect of Pharmacogenetics on Remission rate for Severe Mood Disorders: A Randomised Controlled Trial
Secondary ID [1] 303235 0
Nil known
Universal Trial Number (UTN)
U1111-1264-0949
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe Mood Disorders 320390 0
Major Depressive Disorder 322844 0
Bipolar Disorder 322845 0
Condition category
Condition code
Mental Health 318296 318296 0 0
Depression
Public Health 320425 320425 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CNSDose (formerly known as Amplis – EVO™ Mental Health genetic test) is pharmacogenetic-based clinical decision support tool. Pharmacogenetic-based decision support tools provide information that are relevant for selecting drugs and/or dosage and can also provide information on drug-drug interactions (based on the patient’s current medication regime) in addition to reporting on genotype profile and predicted phenotype. The test includes assays for 16 genes (CYP2D6, CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5, CYP2B6, UGT1A1, ABCB1, ABCC1, ABCG2, CES1, COMT, OPRM1, SLCO1B1 & VKORC1) involved in the metabolism and transport of antidepressant medication. Genetic material is provided from a buccal (cheek) cell sample which involves a simple swab of the inside of the cheeks with a sterile cotton swab. Treating clinicians will receive a report based on analysis of the genetic sample. The report will contain an antidepressant guidance section and a current regimen risk chart which includes genetic and non-genetic risk components. This tool can assist clinicians prescribing decisions in the treatment of severe mood disorders by reducing the risks of adverse medical reactions, support the selection of optimal first-time treatment and avoid polypharmacy issues in elderly patients.

Once eligibility for the study is confirmed and informed consent obtained, participants will be randomised into one of two groups:

Group 1 - CNSDose-guided prescribing
In addition to standard care, participants assigned to this arm will have their pharmacotherapy guided by the CNSDose report based on their genetic test. The genetic test involves a simple buccal swab which takes about 5 minutes and will be sent to the lab on the same day for processing. The lab processing will take about 3 days. The results of the CNSDose test (contained in a report) will be sent to the treating clinicians within a week of the swab to enable tailoring of pharmacotherapy. However use of the CNSDose report is not mandatory for clinicians. At the end of the study (or early withdrawal of a participant), the patients' files will be audited to check if the CNSDose report was used to guide pharmacotherapy and if so, any effects it might have had. Participant adherence to medication will be monitored using the Morisky Medication Adherence Scale which will be administered at each of the 4 follow-up study visits after the baseline visit.

Group 2 - Standard prescribing (unguided)


Following randomisation, participants will provide a Buccal Swab for genetic testing and completed a health questionnaire, depression rating scale, mania rating scale (only for participants with a diagnosis of Bipolar Disorder) and have their vital signs recorded. These assessments will be repeated at 4 weekly intervals until week 12, then again at week 24 as well as complete a medication-taking adherence scale and a side effects rating scale.

All assessments will be conducted by an experienced Trial Coordinator and Study Investigator. Participant visits will be aligned with their regular outpatient visits where possible. If this is not possible then the participant follow-up visits can be conducted remotely i.e. over the phone or via web-based platform if the participant can not make it to the site.
Intervention code [1] 319539 0
Early detection / Screening
Comparator / control treatment
Group 2 - Standard prescribing (unguided)
Participants assigned to this arm will receive standard care as per hospital protocol without the support of the CNSDose report. The CNSDose test results will not be delivered to their treating clinician until either after they complete the study (after their 24-week follow-up assessment) or withdraw early from the study.
Control group
Active

Outcomes
Primary outcome [1] 326273 0
A 10% difference in remission rate for patients with Major Depressive Disorder (MDD) indicated by a Montgomery-Asberg Depression Rating Scale (MADRS) score of less than 10.
Timepoint [1] 326273 0
This outcome will be measured at enrolment (week 0), and weeks 4, 8, 12 and 24 (primary timepoint) post-enrolment.
Primary outcome [2] 329008 0
A 10% difference in remission rate for patients with Bipolar Disorder (BD) indicated by a Young Mania Rating Scale (YMRS) score of less than or equal to 12.
Timepoint [2] 329008 0
This outcome will be measured at enrolment (week 0), and weeks 4, 8, 12 and 24 (primary timepoint) post-enrolment.
Secondary outcome [1] 390861 0
A change in the response rate defined as a greater than or equal to 50% in the MADRS score
Timepoint [1] 390861 0
This outcome will be measured at enrolment (week 0), and weeks 4, 8, 12 and 24 post-enrolment.
Secondary outcome [2] 390862 0
A change in the treatment dropout rate as all-cause discontinuation during the treatment period in the CNSDose group compared with the unguided group.
Timepoint [2] 390862 0
This outcome will be assessed at weeks 4, 6, 8, 12 and 24 post enrolment by a combination of an audit of patients' medical files and telephone follow-up calls.
Secondary outcome [3] 401149 0
Change in treatment outcomes, specifically change in depression severity during the study period. This will be assessed by completion of the nine item Patient Health Questionnaire (PHQ-9).
Timepoint [3] 401149 0
This outcome will be measured at enrolment (week 0) and weeks 4, 6, 8, 12 and 24 post-enrolment.
Secondary outcome [4] 401153 0
The rate of medication side effects will be monitored by completion of the Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale.
Timepoint [4] 401153 0
This outcome will be assessed at weeks 4, 8, 12, and 24.
Secondary outcome [5] 401154 0
Vital signs will be assessed for the study period as part of safety parameter monitoring of medication. This will include: blood pressure and heart rate (using a blood pressure machine), oxygen saturation (using a pulse oximeter), temperature (using tympanic thermometer), respiratory rate (manual count of breaths/min) and body/mass index calculated from weight (using a calibrated digital scale) and height (using a stadiometer).
Timepoint [5] 401154 0
These outcomes will be measured at enrolment (week 0) and weeks 4, 8, 12, and 24 post-enrolment. However, in the event that participants are unable to attend the study site in person for their follow-up visits (i.e. Weeks 4, 8, 12 and 24, the vital signs will not be collected.
Secondary outcome [6] 401155 0
The effects of participants' genetic profile on their reaction to medication will be assessed by having a buccal swab.
Timepoint [6] 401155 0
This test will only be done at enrolment (week 0).
Secondary outcome [7] 401156 0
Adverse event monitoring will be performed as part of the medication safety parameters. This will be done through a combination of patient interview at study visits and audit of patient files.
Timepoint [7] 401156 0
This will be assessed at enrolment (week 0), and weeks 4, 8, 12, and 24 post-enrolment.
Secondary outcome [8] 401157 0
Medication review will be undertaken during the study period to determine if there have been any changes to medication and dosages. This will be done through a combination of patient interview during the study visits and audit of patient files.
Timepoint [8] 401157 0
This will be conducted at enrolment (week 0) and weeks 4, 8, 12, and 24 postt-enrolment.
Secondary outcome [9] 412147 0
A change in the response rate defined as a greater than or equal to 50% in YMRS score
Timepoint [9] 412147 0
This outcome will be measured at enrolment (week 0), and weeks 4, 8, 12 and 24 post-enrolment,

Eligibility
Key inclusion criteria
1. Have a primary diagnosis of MDD or BD.
2. Are currently experiencing a manic, mixed or depressive episode (for those with
BD diagnosis)
3. Are admitted or referred to the participating site
4. Have been prescribed or willing to be prescribed an antidepressant and/or
mood stabiliser
5. Are aged 18 years or older
6. Sufficiently proficient in English to enable completion of the self-reported
study assessment tools.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Are unable to give informed consent
2. If they are clinically unstable or lacking decision-making capacity in the opinion of their
treating clinician
3. Are unwilling to provide a buccal swab sample
4. Have significant neurological disorders (e.g. stroke, dementia, Parkinson’s disease)
5. Have liver disease (e.g. hepatitis, cirrhosis)
6. Are pregnant or planning on becoming pregnant during the trial period

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)
Randomisation will be generated by a member of the central Research team not involved in the day to day operations of the project.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a table created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Analyses will be undertaken on an intention-to-treat basis. The unit of inference will be the individual participants. Generalized linear (logistic) mixed models will be used to compare the probability of remission and side effects between study arms while adjusting for relevant covariates. This analysis approach was selected because it accounts for clustering of participants within clinicians, and provides unbiased estimates in the presence of missing data. For all analyses, adjusted models will be employed if any imbalances in demographic (e.g. age, gender, ancestry) or clinical (e.g. duration of illness) factors are detected between the trial arms.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/01/2022
Actual
18/02/2022
Date of last participant enrolment
Anticipated
30/09/2025
Actual
Date of last data collection
Anticipated
30/09/2025
Actual
Sample size
Target
498
Accrual to date
316
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18478 0
Albert Road Clinic - Melbourne
Recruitment postcode(s) [1] 32796 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 307645 0
Charities/Societies/Foundations
Name [1] 307645 0
Ramsay Hospital Research Foundation
Country [1] 307645 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Parkville VIC 3010
Country
Australia
Secondary sponsor category [1] 308335 0
None
Name [1] 308335 0
Address [1] 308335 0
Country [1] 308335 0
Other collaborator category [1] 281965 0
Commercial sector/Industry
Name [1] 281965 0
Incite Genomics
Address [1] 281965 0
Suite 3/33 Malmsbury St
Hawthorn VIC 3122
Country [1] 281965 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307684 0
Bellberry Limited
Ethics committee address [1] 307684 0
Ethics committee country [1] 307684 0
Australia
Date submitted for ethics approval [1] 307684 0
30/08/2021
Approval date [1] 307684 0
24/12/2021
Ethics approval number [1] 307684 0
2020-05-470

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

Contacts
Principal investigator
Name 108130 0
Prof Malcolm Hopwood
Address 108130 0
Professorial Psychiatry Unit
Albert Road Clinic
31 Albert Road
Melbourne VIC 3004
Country 108130 0
Australia
Phone 108130 0
+61 03 9279 3518
Fax 108130 0
Email 108130 0
mhopwood@unimelb.edu.au
Contact person for public queries
Name 108131 0
Angela Komiti
Address 108131 0
Albert Road Clinic
Research Unit
31 Albert Road
Melbourne VIC 3004
Country 108131 0
Australia
Phone 108131 0
+61 03 9279 3569
Fax 108131 0
Email 108131 0
research.arc@ramsayhealth.com.au
Contact person for scientific queries
Name 108132 0
Malcolm Hopwood
Address 108132 0
Professorial Psychiatry Unit
Albert Road Clinic
31 Albert Road
Melbourne VIC 3004
Country 108132 0
Australia
Phone 108132 0
+61 03 9279 3518
Fax 108132 0
Email 108132 0
mhopwood@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Study outcomes data.
When will data be available (start and end dates)?
Data will be available from the first peer-reviewed journal publication of results (after completion of the study) and available for 15 years after the last publication from the study.
Available to whom?
The public
Available for what types of analyses?
Only to meet the aims of the approved protocol.
How or where can data be obtained?
By contacting the Principal Investigator - Prof Malcolm Hopwood by email: mhopwood@unimelb.edu.au


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.