Major Depressive Disorder: Early Prediction of Non-response to Antidepressant Therapy Via a Mobile Digital Scale

Study Overview
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Brief Summary
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Major Depressive Disorder (MDD) is a debilitating disease characterized by a depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects about 6% of the adult population worldwide each year. Standard symptoms scales like the Hamilton Depression Rating Scale or the Montgomery-asberg Depression Rating Scale, the Self-Report 16-item Quick Inventory of Depressive Symptomatology were initially developed for the evaluation of a therapeutic intervention or a pharmacological treatment and are routinely used by clinicians in the assessment of Treatment Resistant Depression (TRD) occurrence. In parallel, patient-reported outcomes have gained increasing importance and are widely recommended by health authorities in the assessment of depression. The same institutions insist on the collection of real-world data to provide clinicians with ecological measurements. It has been demonstrated that an early response to an AntiDepressant (AD) treatment can be seen as early as week 2 and is not related to a placebo-effect. While there is no consensus on the exact cut-off values, several factors emerge as early predictors of a later treatment response, such as: Improvement in emotional processing of happy facial expressions after 1 week of treatment, Circa 20% improvement in Hamilton Depression Rating Scale-17 item (HDRS-17) at week 2. The hypothesis is therefore that repeated, systematic and real-time, contextualized and multimodal collection of depressive symptoms from patients at home will establish a threshold score that can predict a subsequent response to their treatment. REDRESS was inspired by several standard depression scales used and recommended by the French Health Authority, augmented with digital active and passive activity monitoring, speech analysis and emotional processing assessment. Another important assumption is that honesty and willingness to disclose personal or embarrassing things will be best achievable via a digital solution. To test this assumption, the overall scores and each subscores on the REDRESS numerical scale will be compared in people with MDD showing adequate response to those showing insufficient response. The response to treatment at week 6 will be studied (end of Phase 1). Non-responders and responders to the first treatment round will be enrolled in a 6-week extension phase (Phase 2). Non-responders will receive another treatment course (Other AD, combination, etc.). Responders will just be followed up and will keep the same treatment. The REDRESS scores will be analysed in this population and will allow us to test the investigator's assumption in people with treatment resistant depression. This study will also allow to assess patients' quality of life at the end of each phase of treatment and to compare results with REDRESS scores.

Official Title
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Major Depressive Disorder: Early Prediction of Non-response to Antidepressant Therapy Via a Mobile Digital Scale

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Other: Digital Assessment on mobile


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 70 Years Diagnostic and Statistical Manual of Mental Disorders-5 criteria for MDD Score > 21 on HDRS-17 Initiation of an antidepressant treatment for the current episode (first line or second line treatment, ...) Ability to use a mobile application Agreement to use the study mobile if he/she does not own an iPhone 5 or newer Enrolled in or benefiting of a Social Security program Having read the information sheet and signed the informed consent form Non inclusion Criteria: Serious suicidal risk, identified by the Mini International Neuropsychiatric Interview (MINI) Perinatal depression Seasonal affective disorder Psychiatric comorbidities: bipolar disorder, obsessive-compulsive disorder, post-traumatic stress, psychotic disorder, anorexia nervosa, bulimia nervosa, personality disorder identified by the MINI questionnaire Alcohol addiction or abuse, identified by the MINI questionnaire Substance related disorders non-alcoholic addiction or abuse (opioids, cocaine, cannabis, sedatives, stimulants, hallucinogens, inhalants, solvents), identified by the MINI questionnaire Under neurostimulation (< 6 months before inclusion day) Patient under Temporary Use Authorisation (TUA) Patients with Monoamine Oxidase Inhibitor (MAOIs), tricyclic antidepressant Patient with electroconvulsive therapy (ECT) history for current episode Patient with a somatic pathology Scheduled hospitalization for more than 7 days Antecedent of major head trauma Seizures Systemic medical diseases that are likely to affect cognitive functioning Pregnant and nursing women Wearers of pacemakers, implantable defibrillators Subjects not proficient in French Person under guardianship or curators Illiterate subjects Participation to another interventional clinical trial (category 1) Exclusion criteria: Serious suicidal risk, according to clinician's judgement Discontinuation or change of AD treatment before 4 weeks after the dose initiation in the phase 1 and 2 Initiation of a structured psychotherapy or neurostimulation Initiation of treatment with MAOIS Introduction of benzodiazepines at regular doses. Limited use (≤7 consecutive days or several periods of ≤3 consecutive days) is authorized Alcohol and substances abuse related disorders (opioids, cocaine, cannabis, sedatives, stimulants, hallucinogens, inhalants, solvents), according to clinician's judgement. Patient under Temporary Use Authorisation (TUA)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with Major Depressive Disorder<br>Patients will be followed for 12 weeks. Hospital visits will be made at week 2 and week 6 (Phase1) as well as week 8 and week 12 (Phase 2). At the end of phase 1 if the patient is considered as an responder he will make one more visit at week 12. If the patient is considered as non-responder, he will make 2 other visits: at week 8 and week 12. Between each visit, the patient will perform REDRESS application assessments every day for My daily survey and every 3 days for the other assessments. | Other: Digital Assessment on mobile<br>* The digital assessment is composed on 5 tests: My daily survey My evaluation My cognition My emotions My voice Data will also be collected passively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Show that responders and non-responders in phase 1, have a different early profile on some of the items assessed by REDRESS at week 2 (or before) and identify the predictor item(s). | Identification of items will be based on the diagnostic performance (AUC). | From Day 0 to Week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Show that responders and non-responders in phase 1 have a different profile on some of the items assessed by REDRESS at week 6 and identify the discriminating item(s). | Identification of items will be based on the diagnostic performance (AUC). | From Day 0 to Week 6 | 
| Reproducibility: show that responders and non-responders in phase 2 have a different profile on some of the items assessed by REDRESS at week 8 and identify the same predictor item(s) found in phase 1. | Identification of items will be based on the diagnostic performance (AUC). | From Week 6 to Week 8 | 
| Reproducibility: show that responders and non-responders in phase 2 have a different profile on some of the items assessed by REDRESS at week 12 and identify the same discriminating item(s) found in phase 1. | Identification of items will be based on the diagnostic performance (AUC). | From Week 6 to Week 12 | 
| Intra-patient comparison phase 1 / phase 2: show that patients non-responding in phase 1 and responding in phase 2 have a different profile on some of the items assessed by REDRESS | Intra patient comparison will be based on a paired comparison test. | Between Week 6 and Week 12 | 
| Intra-patient comparison phase 1 / phase 2: show that patients non-responding in phase 1 and responding in phase 2 have a different profile on some of the items assessed by REDRESS | Intra patient comparison will be based on a paired comparison test. | Between Week 2 and Week 8 | 
| Build up a composite score (the REDRESS digital score), from the item(s) identified in the previous objectives. | Ability of the REDRESS digital score to identify responders and non-responders will be based on the diagnostic performance. The REDRESS digital score will be built using the 5 assessments: My Daily Survey, My Evaluation, My Cognition, My Emotion, My Voice and passive data collection. This score will be constructed during the study. | Week 2, Week 6, Week 8 and Week 12 | 
| Evaluate patients' adherence to the mobile application | Patients' adherence to the REDRESS mobile application will be based on the number of questionnaires administered and completed and the number of variables collected via the mobile application as a function of time of follow-up. | From Day 0 to Week 12 | 
| Evaluate the adverse events of the mobile application use. | Mobile application safety will be assessed by a descriptive analysis. | From Day 0 to Week 12 | 
| Collect patients and investigators feedback (usability, satisfaction) on the REDRESS mobile application | Descriptive analysis of patients and investigators satisfaction relating to the mobile application collected with satisfaction questionnaires | Week 12 | 
| Evaluate patient's social relationship | The quality of life will be measure with the form Work and Social Adjustment Scale (WSAS). This scale measures : ability to work, home management, social leisure activities, private leisure activities and close relationships. A WSAS score above 20 appears to suggest moderately severe or worse psychopathology. Scores between 10 and 20 are associated with significant functional impairment but less severe clinical symptomatology. Scores below 10 appears to be associated with subclinical populations. The maximum score of the WSAS is 40. | Day 0, Week 6 and Week 12 | 
| Evaluate patient's quality of life | The quality of life will be measure with the form Quality of Life Enjoyment. This questionnaire is designed to help assess the degree of enjoyment and satisfaction experienced during the past week. This scale mesures : physical health, mood, work, household activities, social relationship, family relationship, leisure time activities, ability to function in daily life, sexual drive, living situation, ability to do work or hobbies, medication. | Day 0, Week 6 and Week 12 | 
| Evaluate the patient's quality of life evolution | The quality of life will be measure with the form Work and Social Adjustment Scale (WSAS). This scale measures : ability to work, home management, social leisure activities, private leisure activities and close relationships. A WSAS score above 20 appears to suggest moderately severe or worse psychopathology. Scores between 10 and 20 are associated with significant functional impairment but less severe clinical symptomatology. Scores below 10 appear to be associated with subclinical populations. The maximum score of the WSAS is 40. | From Day 0 to Week 12 | 
| Evaluate patient's social relationship evolution | The quality of life will be measure with the form Quality of Life Enjoyment. This questionnaire is designed to help assess the degree of enjoyment and satisfaction experienced during the past week. This scale mesures : physical health, mood, work, household activities, social relationship, family relationship, leisure time activities, ability to function in daily life, sexual drive, living situation, ability to do work or hobbies, medication. | From Day 0 to Week 12 | 
| Explore correlation between patient's quality of life and REDRESS score | The correlation will be evaluated with the pearson correlation | Day 0, Week 6 and Week 12 | 
| Evaluate patient's quality of life | The quality of life will be measure with the form Dimensional Anhedonia Rating Scale. This scale measure anhedonia in the context of Major Depressive Disorder. The DARS assesses anhedonia across 4 domains: Hobbies, Food/Drink, Social Activities and Sensory Experiences. The total score of the DARS ranges from 0-68. | Day 0, Week 6 and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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REDRESS, Depression, Application, Mobile