Clinical trial NCT02790970: Predicting Response to Depression Treatment (PReDicT)
Official title: Interventional, Randomised, Open Label, Multi-centre, Parallel-group, Controlled Study Investigating the Effects of Using the PReDicT Test to Guide the Antidepressant Treatment of Depressed Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Lead sponsor: P1vital Products Limited
Sponsor class: INDUSTRY
First posted: 2016-06-06
Enrollment: 913
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Depression is a very common, serious and in some cases life-threatening condition, affecting around 350 million people globally. Approximately 11% of citizens in the European Union suffer from depression at some point in their lives. Depression is associated with significant socio-economic costs and has been predicted to become the greatest cause of disability worldwide by 2030 . In 2010 it was estimated that there were approximately 30 million patients with depression in Europe, with aggregated economic costs of approximately €92 billion . Improvements in managing the treatment of depression are urgently needed to improve patient outcomes, contain rising healthcare costs, improve workplace productivity and help to address global economic and societal challenges.

While a range of effective antidepressant medications are available to treat depression, it takes 4-6 weeks after starting antidepressant treatment before a physician can detect whether the treatment is working. However, surprisingly, more than 50% of patients fail to respond to the first antidepressant treatment they are prescribed. Therefore, it often takes several months to identify an effective antidepressant treatment for the majority of patients with depression. During this time a patient's ability to work and function socially is severely impaired. Individuals may be absent from work for many weeks or months and this places a substantial burden on the economy and on healthcare resources.

Detailed description: The study is a randomized, two-arm, multi-centre, open label, clinical investigation of a medical device, the Predicting Response to Depression Treatment Test (PReDicT Test) . It will be conducted in depressed patients in primary care settings in five European countries (UK, France, Spain, Germany and the Netherlands).

The study is divided into an 8 to 10 week clinical phase and a 40 week follow-up phase. Each participant will be in the study for a total of up to 48-50 weeks.

During the clinical phase, participants will attend between 2 and 4 study visits, depending on their study arm and their response to treatment. Some of these visits may be conducted by telephone. Participants will also complete weekly online questionnaires from home.

During the follow-up phase participants will complete online questionnaires from home every 4 weeks over a 40 week period. Study visits will not be required during the follow-up phase.

An electronic Patient Reported Outcomes (ePRO) system, accessed via a study website, will be used to collect questionnaire data and PReDicT Test responses. The ePRO system will be used to randomise participants and will issue email reminders to participants and study researchers when study-related activities are due.

Visit 1: Screening and PReDicT #1 The visit will take place at the study site 0 to 7 days after the SSRI was prescribed. Visit 1 may take place on the same day as the Selective Serotonin Reuptake Inhibitor (SSRI) was prescribed only if local approvals permit this to happen. Informed Consent must be obtained before any study procedures are performed. Visit duration will be approximately 90 minutes.

The following will take place at Visit 1:

* Informed Consent
* Unique participant screening number assigned
* Demographics (including age, gender, ethnicity, number of years in higher education, family history of depression)
* Depression history (as applicable), including age at first episode, number of past episodes of depression and time since last episode
* Brief medical history
* Medication history (current medication, medication taken over the past month, any available information on previous antidepressant medications)
* Entry criteria check Participants that do not meet the entry criteria ('screen failures') will leave the study.

Participants that meet the entry criteria will complete the following activities in the order below:

* Montgomery-Åsberg Depression Rating Scale (MADRS)
* Registration of participant on the Electronic Patient Reported Outcomes(ePRO) system (by study researcher)
* Participant creates ePRO system account
* PReDicT Test (which includes the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16) questionnaire from which baseline QIDS-SR-16 scores are obtained)
* Randomisation (by the ePRO system)
* 5 dimensional - 5 Level quality of life questionnaire (EQ-5D-5L)
* Health Economics Questionnaire (HEQ)
* Oxford CAPabilities questionnaire-Mental Health (OxCAP-MH) (UK and Germany only)
* Social Adjustment Scale - Self-Report (screen version) (SAS-SR (screen version))
* Generalised Anxiety Disorder Questionnaire, 7 item version (GAD-7)
* Digit Symbol Substitution Test (DSST)
* Adverse Events (AEs), Adverse Device Effects (ADEs) and device deficiencies will be recorded from the signing of the ICF and continue until week 8.

At the end of the visit, enrolled participants will be asked to start their prescribed SSRI. Dose and frequency will be as prescribed by their physician.

Visit 2 is only required for participants in the PReDicT arm.

* This visit will take place after PReDicT #2 has been completed. It will preferably take place within 1 day (same day is permissible). The visit may be conducted by telephone (if permitted locally) or at the study site. Visit duration will be approximately 5-10 minutes. The following will take place.
* A study researcher will review the PReDicT Test results online.
* If the PReDicT Test results indicate a positive response to the prescribed antidepressant:

  * Antidepressant treatment is not changed.
  * The next study visit is Visit 4 (there is no Visit 3 for this participant).
* If the PReDicT Test results indicate an insufficient response to the prescribed antidepressant:

  * Antidepressant treatment is altered (by a physician) in accordance with locally appropriate guidelines and judgement of the physician (i.e. normally the dose of the current medication is increased).

Visit 3 is only required for participants in the PReDicT arm who have completed PReDicT #3. This visit will be the same as Visit 2.

Visit 4 (All Participants) The visit will take place 8-10 weeks after starting antidepressant treatment. Visit duration will be approximately 60 minutes. All participants will then continue into the online follow-up phase of the study.

The following Visit 4 activities must be completed at the study site and will take approximately 30 minutes.

* MADRS
* Number and dates of non-study clinical visits for depression since Visit 1
* Review of antidepressant medication compliance. Document all changes to dose or type of antidepressant. Refer to ePRO system data. Ensure any discrepancies between eCRF data and ePRO data are explained
* Review of concomitant medication since last visit
* Review of AEs, ADEs and device deficiencies
* Serious Adverse Events (SAEs) and device-related incidents will be followed up as set out in Section 10.0, Adverse Event Reporting. Non-serious AEs will be followed up at the study physician's discretion The following Visit 4 online questionnaires may be completed at home or at the study site. They can take place before or after the other Visit 4 activities. Questionnaires will take approximately 30 minutes to complete.
* QIDS-SR-16
* EQ-5D-5L
* HEQ
* OxCAP-MH (UK and Germany only)
* SAS-SR (screener version)
* GAD-7
* DSST
* Patient Acceptability Questionnaire An email reminder will be sent to each participant at 8 weeks. An alert will be emailed to the study researcher after 2 days if the questionnaire(s) have not been completed. Researchers should contact the participant as soon as possible and ask them to complete the missing questionnaire(s).

Participants will complete the following online questionnaires every 4 weeks for 40 weeks, starting 4 weeks after Visit 4. The questionnaires take approximately 15 minutes (total) to complete.

* QIDS-SR-16
* EQ-5D-5L
* HEQ Participants will complete the following online questionnaires at week 24 and week 48 of the study.
* OxCAP-MH (UK and Germany only)
* SAS-SR (screener version) For all online questionnaires, an email reminder will be sent to each participant on the day that completion of the questionnaires is due. The email will include a link to the questionnaires on the ePRO system.

An alert will be emailed to the study researchers after 2 days if the questionnaire(s) have not been completed. A researcher will contact the participant as soon as possible and ask them to complete the missing questionnaire(s).

To improve study participation and reduce drop-outs, participants in the PReDicT arm of the study will be able to view their QIDS-SR-16 scores on the ePRO system from Visit 4 up to and including the final online follow-up (Follow-Up #10, occurring 40 weeks after Visit 4).

Prescribing physicians and (if relevant) support staff at each study site will be asked to complete a Healthcare Provider Acceptability Questionnaire at around the time that the final participant at their study site completes Visit 4.

The Healthcare Provider Acceptability Questionnaire is a 40-item questionnaire covering their experience of taking part in the study, their experience of using the PReDicT Test in the study and their future intentions regarding the use of the PReDicT Test. Additional space is provided for free-text comments.

In England and Germany, digitally recorded semi-structured interviews will be performed with maximum variance samples of participants (patients), prescribing physicians and (if relevant) support staff. Interviews will be conducted by fluent speakers of English and/or German (as appropriate) and may be carried out face-to-face or by telephone/Skype.

Interviewees will be selected in such a way that there is appropriate representation of factors including age, gender, questionnaire responses, full- and part-time staff, urban and rural location and high/low/non-recruiting study sites.

Approximately 15 to 20 participants, 20-25 prescribing physicians and a small number of support staff (if relevant) will be interviewed. Interviews will be conducted by trained researchers and will take place during and after completion of the clinical phase of the study, depending on whether participants or study staff are being interviewed. Participants will be recruited for interview within 1 to 2 months after they have completed Visit 4. Prescribing physicians and support staff will be interviewed after the end of the clinical phase at their study site (when all participants have been recruited).

Eligibility criteria: Inclusion Criteria:

* Male or female aged between 18 and 70 inclusive.
* Diagnosed with a depressive episode by a physician (either first episode or recurrent) and requiring treatment with a selective serotonin reuptake inhibitor (SSRI) medication (excluding fluoxetine).
* Prescribed an SSRI by a physician for the treatment of depression within 7 days prior to Visit 1, but has not yet started taking medication.
* Is intending to start SSRI treatment within 7 days of Visit 1.

Exclusion Criteria:

* Previous history of mania.
* Is currently taking an antidepressant medication or has stopped antidepressant treatment within 2 weeks prior to Visit 1.
* Requires immediate referral to alternative mental health services (e.g. where a patient seen in primary care is referred to secondary care services).
* Presents to a physician with significant current suicidal intent requiring enhanced care.

Primary outcomes:
measure: Increase in proportion of depressed patients showing a response to treatment at week 8 when using the PReDicT Test to direct antidepressant treatment compared to treatment as usual as measured by the QIDS-SR-16
timeFrame: 8 weeks
Secondary outcomes:
measure: Compare the change from baseline in QIDS-SR-16 scores
timeFrame: 8 weeks
measure: Increase in proportion of depressed patients showing a response to treatment at week 8 when using the PReDicT Test to direct antidepressant treatment compared to treatment as usual as measured by a reduction of >50% in the MADRS score
timeFrame: 8 weeks
measure: Increase in proportion of depressed patients showing remission from depression at week 8 when using the PReDicT Test to direct antidepressant treatment compared to treatment as usual as measured by a QIDS-SR-16 score <=5
timeFrame: 8 Weeks
measure: Compare changes in baseline of the QIDS-SR-16 score
timeFrame: 12 weeks
measure: Compare changes in baseline of the QIDS-SR-16 score
timeFrame: 24 weeks and 48 weeks
measure: Health economic analysis on societal costs and cost-effectiveness/cost-utility of the PReDicT Test compared with Treatment as Usual as measured by the EQ-5D-5L
timeFrame: 24 weeks and 48 weeks (optional)
measure: Health economic analysis on societal costs and cost-effectiveness/cost-utility of the PReDicT Test compared with Treatment as Usual as measured by the QIDS-SR-16
timeFrame: 24 weeks and 48 weeks (optional)
measure: Health economic analysis on societal costs and cost-effectiveness/cost-utility of the PReDicT Test compared with Treatment as Usual as measured by the OxCAP-MH
timeFrame: 24 weeks and 48 weeks (optional)
measure: Health economic analysis on societal costs and cost-effectiveness/cost-utility of the PReDicT Test compared with Treatment as Usual as measured by the HEQ
timeFrame: 24 weeks and 48 weeks (optional)
measure: Obtain further feasibility data
timeFrame: 48 weeks
measure: Assess the acceptability and perceived value of the PReDicT Test
timeFrame: 48 weeks
measure: Compare the change from baseline in GAD-7 score
timeFrame: 8 Weeks
measure: Compare the change from baseline on the depression and anxiety items
timeFrame: 8 weeks
measure: Determine the change of cognitive function
timeFrame: 8 weeks
measure: Compare the change from baseline in self-reported social and occupational functioning
timeFrame: weeks 8, 24 and 48
measure: Device safety as required by medical devices legislation
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre Hospitalier Sainte-Anne
city: Aschaffenburg
country: Germany
facility: Praxis Dr. Hofmann
city: Aschaffenburg
country: Germany
facility: Praxis Wagner
city: Frankfurt am Main
country: Germany
facility: Praxis Dunkel
city: Frankfurt am Main
country: Germany
facility: Agaplesion Markus Krankenhaus
city: Frankfurt am Main
country: Germany
facility: Dept of Psychiatry, Outpatient Clinic, University Hospital
city: Frankfurt am Main
country: Germany
facility: Praxis Dr. Körner
city: Kitzingen
country: Germany
facility: Praxis Dr. Gunreben
city: Lohr
country: Germany
facility: Praxis Dr. Boreatti
city: Mühlheim
country: Germany
facility: Praxis Dr. Vondung
city: Offenbach
country: Germany
facility: Praxis Bayer
city: Offenbach
country: Germany
facility: Praxis Dr. Frühauf
city: Offenbach
country: Germany
facility: Praxis Schell
city: Randersacker
country: Germany
facility: Praxis Dr. Rost
city: Schweinfurt
country: Germany
facility: Praxis Dr. Meesmann
city: Veitshochheim
country: Germany
facility: Praxis Habermeyer
city: Werneck
country: Germany
facility: Schloss Werneck
city: Wurzburg
country: Germany
facility: Department of Psychiatry
city: Wurzburg
country: Germany
facility: Praxis Dr. Heine
city: Wurzburg
country: Germany
facility: Praxis Dr. Kropp
city: Wurzburg
country: Germany
facility: Praxis Dr. Reimann
city: Würzburg
country: Germany
facility: Medizinisches Studienzentrum (MSZ)
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum de Keijzer
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Borgerstraat
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum De Vaart
city: Amsterdam
country: Netherlands
facility: GGZ inGeest
city: Amsterdam
country: Netherlands
facility: Prezens - bGGZ
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Osdorp
city: Amsterdam
country: Netherlands
facility: Huisartsenpraktijk Houben en Zonneveld
city: Amsterdam
country: Netherlands
facility: Huisartsenpraktijk Land
city: Amsterdam
country: Netherlands
facility: Huisartsenpraktijk De Grote Rivieren
city: Amsterdam
country: Netherlands
facility: Dept of Psychiatry, Vumc
city: Amsterdam
country: Netherlands
facility: Universitaire Huisartsenpraktijk VUmc
city: Amsterdam
country: Netherlands
facility: Huisartsenpraktijk MC Gelderlandplein
city: Amsterdam
country: Netherlands
facility: Huisartsenpraktijk Buitenhof
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Venserpolder
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Klein-Gooioord
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Gein
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Reigersbos
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Nellestein
city: Amsterdam
country: Netherlands
facility: Gezondheidscentrum Diemen-Noord
city: IJmuiden
country: Netherlands
facility: De Hoofdlijn
city: Barcelona
country: Spain
facility: CAP Barceloneta
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: CAP Vila Olímpica
city: Barcelona
country: Spain
facility: Centre Fòrum
city: Barcelona
country: Spain
facility: CAP Larrard
city: Midsomer Norton
country: United Kingdom
facility: St Chad's Surgery
state: Bath
city: Pangbourne
country: United Kingdom
facility: The Boathouse Surgery
state: Berkshire
city: Carlisle
country: United Kingdom
facility: Carlisle Healthcare
state: Cumbria
city: Alfreton
country: United Kingdom
facility: The Limes Medical Centre
state: Derbyshire
city: Burbage
country: United Kingdom
facility: Burbage Surgery
state: Leicestershire
city: Lincoln
country: United Kingdom
facility: Lindum Medical Practice
state: Lincolnshire
city: Nettleham
country: United Kingdom
facility: Nettleham Medical Practice
state: Lincoln
city: Welton
country: United Kingdom
facility: Welton Family Health Centre
state: Lincoln
city: Corby
country: United Kingdom
facility: Lakeside Surgery
state: Northamptonshire
city: Daventry
country: United Kingdom
facility: Danetre Medical Practice
state: Northamptonshire
city: Earls Barton
country: United Kingdom
facility: Earls Barton Medical Centre
state: Northamptonshire
city: Rothwell
country: United Kingdom
facility: Rothwell and Desborough Healthcare Group
state: Northamptonshire
city: Wellingborough
country: United Kingdom
facility: Albany House Medical Centre
state: Northamptonshire
city: Atherstone
country: United Kingdom
facility: Atherstone Surgery
state: Warwickshire
city: Leamington Spa
country: United Kingdom
facility: Sherbourne Medical Centre
state: Warwickshire
city: Corsham
country: United Kingdom
facility: The Porch Surgery
state: Wiltshire
city: Trowbridge
country: United Kingdom
facility: Adcroft Surgery
state: Wiltshire
city: Trowbridge
country: United Kingdom
facility: Bradford Road Medical Centre
state: Wiltshire
city: Westbury
country: United Kingdom
facility: Westbury Group Medical Practice
state: Wiltshire
city: Bath
country: United Kingdom
facility: The Pulteney Practice
city: Faversham
country: United Kingdom
facility: Newton Place Surgery
city: Leicester
country: United Kingdom
facility: Thurmaston Health Centre
city: Lincoln
country: United Kingdom
facility: Birchwood Medical Practice
city: Lincoln
country: United Kingdom
facility: Lincoln University Health Care
city: Northampton
country: United Kingdom
facility: Leicester Terrace
city: Northampton
country: United Kingdom
facility: Danes Camp Practice
city: Nottingham
country: United Kingdom
facility: Family Medical Centre
city: Nottingham
country: United Kingdom
facility: University of Nottingham Health Service - Cripps Health Centre
city: Oxford
country: United Kingdom
facility: South Oxford Health Centre
Study officials:
affiliation: P1vital Limited
name: Mike Browning
role: PRINCIPAL_INVESTIGATOR
References:
citation: World Health Organization, The Global Burden of Disease: 2004 update. nDeneva, World Health Organization, 2008.
citation: Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011 Sep;21(9):655-79. doi: 10.1016/j.euroneuro.2011.07.018.
citation: Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007 Feb;164(2):201-4. doi: 10.1176/ajp.2007.164.2.201. No abstract available.
citation: Kingslake J, Dias R, Dawson GR, Simon J, Goodwin GM, Harmer CJ, Morriss R, Brown S, Guo B, Dourish CT, Ruhe HG, Lever AG, Veltman DJ, van Schaik A, Deckert J, Reif A, Stablein M, Menke A, Gorwood P, Voegeli G, Perez V, Browning M. The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial. Trials. 2017 Nov 23;18(1):558. doi: 10.1186/s13063-017-2247-2.