The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000527369
Ethics application status
Approved
Date submitted
5/04/2017
Date registered
11/04/2017
Date last updated
20/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of addition of anti-inflammatory medication to anti-depressant medication in the treatment of depression
Scientific title
Effect of addition of anti-inflammatory medication to anti-depressant medication on C-reactive protein levels in the treatment of depression
Secondary ID [1] 291560 0
Nil known
Universal Trial Number (UTN)
To be announced
Trial acronym
PREDDICT
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Depression 302654 0
Condition category
Condition code
Mental Health 302172 302172 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a randomised controlled treatment (RCT) trial over 8 weeks, with a 6 month post-RCT trial period, where study participants have the option to continue Vortioxetine in the post-RCT trial period. The study aims to investigate whether the use of a blood test of inflammation levels, prior to antidepressant treatment, can improve treatment of depression by guiding the decision to add anti-inflammatory medication to antidepressant treatment.
Specifically, the study aims to find out whether adding the anti-inflammatory medication Celecoxib to the antidepressant medication Vortioxetine can improve symptoms of depression.
At the start of the study, participants would undergo a blood test to measure levels of the inflammatory marker C-reactive protein (CRP). For CRP, a cut-off level of 3mg/L will be used to determine whether participants are assigned to the "Depression with inflammation" arm, or to the "Depression without inflammation" arm. Within each study arm, participants would then be randomly assigned to 6 weeks of treatment with Vortioxetine plus Celecoxib, or Vortioxetine plus placebo.
All study medications are oral tablets. The dose of Vortioxetine is initially 5 mg daily in those receiving Celecoxib, with an option to increase to Vortioxetine 10mg daily 2 weeks into the study (after review by the Psychiatrist, and if it is thought this dose may benefit the study participant). The planned dose of Celecoxib is 400mg daily.
Study participants will be asked at each visit if any doses of study medication have been missed.
Intervention code [1] 297621 0
Treatment: Drugs
Comparator / control treatment
Vortioxetine plus placebo, for a duration of 6 weeks. The comparator / control treatments are also oral tablets. The dose of Vortioxetine is initially 10 mg daily, with an option to increase to Vortioxetine 20 mg daily 2 weeks into the study (after review by the Psychiatrist, and if it is thought this dose may benefit the study participant).
The placebo is a microcellulose tablet.
Control group
Active

Outcomes
Primary outcome [1] 301593 0
Change in MADRS, with a primary endpoint of proportion of study participants with a score reduction by 50% from baseline to 6 weeks (end of treatment).
Timepoint [1] 301593 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [1] 333238 0
Change in C-reactive protein (CRP) levels, with a secondary endpoint of proportion of study participants with a reduction of CRP levels by 50% between baseline and 6 weeks (end of treatment).
Timepoint [1] 333238 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [2] 333417 0
Change in levels of the inflammatory markers TNF-a, IL-6, and IL-1b, measured by enzyme linked immunosorbent assay (ELISA), with a secondary endpoint of proportion of study participants with a reduction of 50% of levels of these inflammatory markers between baseline and 6 weeks (end of treatment).
Timepoint [2] 333417 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [3] 333418 0
Safety of the anti-inflammatory Celecoxib 400 mg when combined with Vortioxetine, with a secondary endpoint of measuring adverse events (AE’s). At each visit, study participants will be asked to report adverse events (e.g. nausea, abdominal pain), and these will all be recorded.


Timepoint [3] 333418 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [4] 333421 0
Assessment of cognitive dysfunction, using the THINC-It tool: -secondary endpoint of proportion of study participants with a 50% improvement in subjective (PDQ-5) and each objective (Spotter, Symbol Check, Codebreaker, Trails) cognitive measure from baseline to 6 weeks.
Timepoint [4] 333421 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [5] 333634 0
Change in Clinical Global Impression-Severity (CGI-S)
Timepoint [5] 333634 0
Baseline (before treatment) and 6 weeks (end of treatment)

Secondary outcome [6] 333635 0
Change in Clinical Global Impression-Improvement (CGI-I)
Timepoint [6] 333635 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [7] 333636 0
Change in functional measures, as assessed by proportion of study participants with a 50% improvement in Functioning Assessment Short Test (FAST) from baseline to 6 weeks (end of treatment)
Timepoint [7] 333636 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [8] 333637 0
Change in WHO-5 Well-being Index, as assessed by proportion of study participants with a 50% improvement from baseline to 6 weeks (end of treatment)
Timepoint [8] 333637 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [9] 333638 0
Change in Sheehan Disability Scale, as assessed by proportion of study participants with a 50% improvement from baseline to 6 weeks (end of treatment)
Timepoint [9] 333638 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [10] 333639 0
Change in workplace functioning, as assessed by proportion of study participants with a 50% improvement in Work Limitations Questionnaire from baseline to 6 weeks (end of treatment)
Timepoint [10] 333639 0
Baseline (before treatment) and 6 weeks (end of treatment)
Secondary outcome [11] 333640 0
Change in workplace functioning, as assessed by proportion of study participants with a 50% improvement in Endicott Workplace Productivity Scale from baseline to 6 weeks (end of treatment).
Timepoint [11] 333640 0
Baseline (before treatment) and 6 weeks (end of treatment)

Eligibility
Key inclusion criteria
1. The study participant is willing and able to provide informed consent.
2. Age 18 – 75 years of age.
3. Diagnosis of a Major Depressive Episode (MDE) as part of Major Depressive Disorder (MDD), using DSM-5 criteria.
4. Montgomery Asberg Depression Rating Scale (MADRS) score greater than or equal to 26 at screening visit and baseline.
5. Duration of the current MDE is at least 3 months.
6. Use of a previous treatment in at least one prior episode of depression
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of a co-morbid psychiatric disorder other than MDD that is a focus of clinical concern as confirmed by the Mini International Neuropsychiatric Interview (MINI).
2. A known relevant inflammatory or immune-related disorder such as rheumatoid arthritis, colitis, clinically significant asthma, multiple sclerosis, SLE, acute infections or fever.
3. A known neurodegenerative disease
4. Any medication for a general medical disorder that may affect cognitive function
5. Electroconvulsive therapy (ECT) within the last 6 months.
6. The study participant has reported having received investigational agents as part of a separate study within 30 days of the screening visit.
7. Contraindications to the study drugs

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)
Allocation is concealed, by the use of central randomisation by phone/ fax/ computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified allocation based on CRP levels at screening (prior to commencement of treatment), with a cut-off level of 3 mg/L to determine whether participants are assigned into the "Depression with inflammation" arm, or the "Depression without inflammation" arm.
Within each arm, the method of sequence generation used will be simple 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
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Given a power of 0.95, and an alpha error of 0.05, the study sample size required to detect a change in MADRS of an effect size of 0.25 between baseline and week 6 would be 50 study participants in each of the four groups. This would be a total of 200 study participants (100 participants in the “Depression with inflammation” arm, and 100 study participants in the “Depression without inflammation” arm; 50 participants in each treatment group respectively).

The primary outcome will be analysed using a mixed model for repeated measurements, using all available data. The baseline CRP level and stratified group (“Depression with inflammation” vs “Depression without inflammation”) will be used as a covariate.
The potential treatment effect on CRP will be separated into the stratified arms (“Depression with inflammation” vs “Depression without inflammation”), as well as for total group (all 4 groups).
For dichotomous endpoints, such as response and remission, logistic regression with treatment as a factor and the baseline score as a covariate will be used.
For continuous endpoints, the same methodology as that described for the primary endpoint will also be used. Continuous endpoints will also be analysed using an ANCOVA (OC and last observation carried forward (LOCF)).

Recruitment
Recruitment status
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)
SA
Recruitment hospital [1] 7766 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 15699 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 296049 0
University
Name [1] 296049 0
University of Adelaide
Address [1] 296049 0
University of Adelaide
North Terrace
Adelaide
South Australia, 5005
Country [1] 296049 0
Australia
Primary sponsor type
Individual
Name
Professor Bernhard Baune
Address
Professor Bernhard Baune
Chair, Discipline of Psychiatry
University of Adelaide
Level 7, Adelaide Health and Medical Sciences Building
North Terrace
Adelaide
South Australia, 5000
Country
Australia
Secondary sponsor category [1] 294984 0
None
Name [1] 294984 0
Address [1] 294984 0
Country [1] 294984 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297305 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 297305 0
Ethics committee country [1] 297305 0
Australia
Date submitted for ethics approval [1] 297305 0
27/03/2017
Approval date [1] 297305 0
25/05/2017
Ethics approval number [1] 297305 0
HREC/17/RAH/111
Ethics committee name [2] 298365 0
University of Adelaide HREC
Ethics committee address [2] 298365 0
University of Adelaide
Adelaide, SA
Ethics committee country [2] 298365 0
Australia
Date submitted for ethics approval [2] 298365 0
09/06/2017
Approval date [2] 298365 0
13/06/2017
Ethics approval number [2] 298365 0

Summary
Brief summary
The study is a randomised controlled treatment (RCT) trial over 8 weeks in individuals with Major Depressive Disorder, with a 6 month post-RCT trial period, where study participants have the option to continue Vortioxetine.
The purpose of the study is to investigate the effectiveness of using a simple blood test, prior to treatment of depression, to guide the use of anti-inflammatory medication as an addition to antidepressant medication.
The study aims to find out whether adding the anti-inflammatory medication Celecoxib (also known as Celebrex) to the antidepressant medication Vortioxetine (also known as Brintellix) can improve symptoms of depression.
There is evidence that raised levels of inflammatory markers in the blood are associated with depression. The study measures the inflammatory marker C-reactive protein (CRP) prior to commencing treatment, with study participants assigned to a study "arm" based on CRP levels. Within each study "arm", participants receive treatment for 6 weeks, with either Vortioxetine plus Celecoxib, or Vortioxetine plus placebo.
Levels of circulating inflammatory markers, tests of cognitive function, and depression symptoms are measured at baseline (before treatment) and again at the end of this 6 week treatment period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73650 0
Prof Bernhard Baune
Address 73650 0
Discipline of Psychiatry School of Medicine University of Adelaide Adelaide, SA, 5000
Country 73650 0
Australia
Phone 73650 0
+61 448 757 873
Fax 73650 0
Email 73650 0
bernhard.baune@adelaide.edu.au
Contact person for public queries
Name 73651 0
Dr Natalie Mills
Address 73651 0
Discipline of Psychiatry School of Medicine University of Adelaide Adelaide, SA, 5000
Country 73651 0
Australia
Phone 73651 0
+ 61 8 8313 7676
Fax 73651 0
Email 73651 0
natalie.mills@adelaide.edu.au
Contact person for scientific queries
Name 73652 0
Prof Bernhard Baune
Address 73652 0
Discipline of Psychiatry School of Medicine University of Adelaide Adelaide, SA, 5000
Country 73652 0
Australia
Phone 73652 0
+61 448 757 873
Fax 73652 0
Email 73652 0
bernhard.baune@adelaide.edu.au

No data has been provided for results reporting
Summary results
Not applicable