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NCT Number: NCT05866575

Prediction of the Therapeutic Response in Depression Based on Neuro-computational Modeling Assessment of Motivation

This study aims to better understand the mechanisms of action of antidepressants, but also the neural correlates of motivation deficits. One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. The objective will be to predict the therapeutic response to two first-line antidepressants on the basis of an early neurocomputational assessment of motivation. Antidepressant treatment will be administered as monotherapy after randomization between two drugs: escitalopram and vortioxetine. Patients will undergo six visits and follow-up for one year. The investigators will combine computer modeling and functional MRI to identify motivational deficits and elucidate their brain correlates before initiation, after 7 days and after 6 months of treatment. 36 healthy volunteers will also be included to allow comparison with patients with depression. They will not receive any treatment.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Groupe hospitalo-universitaire de Grenoble Alpes, La Tronche, Isère, France

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About this study

One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. Six visits will be scheduled within a year:

  • V0 (inclusion visit): verification of inclusion and exclusion criteria, information, and consent.
  • V1 (before randomization - baseline state):
  • Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
  • Neuro-cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating. Part of the tests will be performed during the functional MRI session.
  • Structural (anatomical) and functional MRI, ASL.
  • Blood samples.
  • Randomization and introduction of the new antidepressant will occur immediately after V1. To maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the assigned treatment will not be changed for 4 weeks (until V3).
  • V2 (7 days after the beginning of the new antidepressant - 'early response visit'):

o Similar to V1.

  • V3 (28 days after the beginning of the new antidepressant - 'conventional response visit'):
  • Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
  • Blood samples
  • V4 (6 months after the beginning of the new antidepressant - 'remission visit'):
  • Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
  • Cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating.
  • Structural (anatomical) MRI, ASL
  • Blood samples
  • V5 (one year after the beginning of the new antidepressant - 'functional remission visit'):
  • Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.

36 healthy volunteers without a history of neurologic or psychiatric disorder, matched for age, gender, and education will be included. They will perform V0-V2 (without MRI and blood sample at V2). Healthy volunteers will not receive any treatment as part of the research.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Patients with major depressive disorder

Inclusion criteria

  • Meeting DSM-5 criteria for major depressive disorder (single or recurrent episodes)
  • With a MADRS score >= 24
  • For which a new line of treatment is needed
  • No previous line of antidepressant for this episode or wash-out long-enough to avoid carry-over effects
  • Valid health care insurance

Exclusion criteria

  • Treatment-resistant depression (defined as insufficient response despite at least 2 trials of antidepressant prescribed at adequate dose and duration)
  • Subjects with a trial of escitalopram and/or vortioxetine for the current episode, or with contra-indication to one of these two drugs
  • Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
  • Subject with a history of neurological disorder: parkinson's disease, dementia
  • Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
  • Pregnant or breastfeeding women
  • involuntary hospitalisation and legal protection measures

Healthy volunteers

Inclusion criteria

  • Valid health care insurance

Exclusion criteria

  • Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
  • Subject with a history of neurological disorder: parkinson's disease, dementia
  • Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
  • Pregnant or breastfeeding women

Treatment and study plan

escitalopram

Other

Patients will receive an antidepressant strategy : escitalopram. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.

vortioxetine

Other

Patients will receive an antidepressant strategy : vortioxetine. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the treatment strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.

Primary outcomes

  1. Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the computational phenotype of depressed patients.

    Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)

    The therapeutic response will be measured with the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is a 10- item scale widely used in depression research to assess the severity of depression. Response will be defined by a score divided by 2 compared to baseline MADRS score, while remission will be defined by a score < 7 (symptom absent) 28 days after the initiation of the antidepressant strategy.

    The "computational phenotype" is the outcome of the computationnal analysis of behavior. It is expressed in abstract unit. The change in computationnal phenotype between V1 and V2 will be entered in logistic regression aiming to predict clinical response at 28 days, measured with the MADRS score.

Secondary outcomes

  1. Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the neuro-computational phenotype of depressed patients

    Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)

    Same than outcome 1 but using brain imaging on top of behavior (neurocomputational modeling) to predict clinical response.

  2. Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the initial (baseline state- V1) neuro-computational phenotype of depressed patients

    Time frame: Baseline state (before the start of antidepressant strategy), and V3 (after 28 days of antidepressant)

    Same than Outcome 2 but using only V1 instead of the change between V1 and V2 to predict clinical response.

  3. Prediction of long-term remission (V4) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients

    Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V4 (6 months after the start of antidepressant)

    Same than Outcome 2 but to predict clinical remission at V4 instead of clinical response at V3.

  4. Prediction functional remission (V5) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients

    Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V5 (1 year after the start of antidepressant)

    Same than Outcome 2 but to predict functional remission at V5 instead of clinical response at V3.

  5. Prediction of relapse at one year (V5) based on the computationnal phenotype of remitted patients at 6 months (V4).

    Time frame: V4 (6 months after the start of antidepressant), V5 (1 year after the start of antidepressant)

    Same than Outcome 1 but using computational phenotype at V4 to predict predict functional remission at V5.

  6. Description of the motivational deficit of depressed patients at baseline (V1).

    Time frame: Baseline state (before the start of antidepressant strategy)

    Comparison of the computational phenotype of patients with depression and healthy volunteers at V1.

  7. Description of the neural correlates of motivation deficits of depressed patients at baseline (V1).

    Time frame: Baseline state (before the start of antidepressant strategy)

    Comparison of the brain functional statistical maps of patient with depression and healthy volunteers at V1.

  8. Description of the evolution of motivation deficit of depressed patients after one week of antidepressant treatment

    Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)

    Comparison of the computational phenotype of patients with depression at V1 and V2.

  9. Description of the evolution of the neural correlates of motivation deficits after one week of antidepressant treatment

    Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)

    Comparison of the brain functional statistical maps of patient with depression at V1 and V2.

  10. Description of the evolution of motivation deficit of depressed patients at 6 months

    Time frame: Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)

    Comparison of the computational phenotype of patients with depression at V1 and V4.

  11. Description of the evolution of the structural neural correlates of depression after 6 months of treatment

    Time frame: Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)

    Comparison of the structural brain imaging of patients with depression at V1 and V4.

  12. Description of the evolution of the functional neural correlates of depression after 6 months of treatment

    Time frame: Baseline state (before the start of antidepressant strategy) V4 (6 months after the start of antidepressant)

    Comparison of the function brain imaging (ASL) of patients with depression at V1 and V4.

  13. Construction of a bio-bank

    Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant), V4 (6 months after the start of antidepressant)

    Serum tubes will be drowned along the study (V1, V2, V3 and V4 for patients - V1 for healthy volunteers) prepared and stored.

Study contacts

Contact information is provided by the study sponsor or research team.

Claire Jaffré

CONTACT

[email protected]

0033650557373

Fabien Vinckier

CONTACT

[email protected]

0033683714083

Sponsors and collaborators

Lead sponsor

Centre Hospitalier St Anne

Other

Registry information

Official study title

Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation

Acronym: STRATIDEP

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
May 19, 2023
Registry last updated
Jul 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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