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NCT Number: NCT07741981

Treatment Resistance in Psychiatric Disorders: the Search for Biological Markers Predictive of Response to Treatment

The disruption of immune system is a key candidate in the pathogenesis of psychiatric disorders, especially those resistant to traditional treatments. Involving complex processes within the brain and peripheral immune system, inflammation may lead to imbalance of neurotransmitter systems and synaptic plasticity and directly contribute to the psychiatric symptoms observed in conditions such as depression, bipolar disorder (BD) and schizophrenia (SCZ).

Studies show that treatment-resistant depression (TRD) is associated with elevated levels of inflammatory markers in the blood, which are linked to a lower response to conventional antidepressants. Interventions that modulate this inflammatory response, such as immunomodulatory treatments or therapies targeting pro-inflammatory cytokines, have demonstrated beneficial effects by reducing symptoms and improving patients' quality of life.

A thorough understanding of the links between inflammation and treatment resistance therefore paves the way for innovative therapeutic strategies. These approaches could transform current practices by offering more personalized and effective solutions for patients suffering from chronic and resistant psychiatric disorders.

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Key information

Conditions

Schizophrenia Anxiety Disorders Behavior Behavioral Symptoms Bipolar Disorder Bipolar Disorder (BD) Bipolar and Related Disorders Catatonia Depressive Disorder Depressive Disorder, Treatment-Resistant Mental Disorders Mood Disorders Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Obsessive Compulsive Disorder (OCD) Obsessive-Compulsive Disorder Pathological Conditions, Signs and Symptoms Schizophrenia Spectrum and Other Psychotic Disorders Signs and Symptoms Treatment Resistant Depression (TRD)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Patient aged ≥ 18 years old;
  • Patient suffering from a psychiatric disorder according to DSM-5 criteria;
  • Patient with drug-resistant disease according to the definition of the protocol
  • Patient starting a new treatment for his pathology;
  • Patient informed and having signed an informed consent;
  • Patient covered by the social security system.

Exclusion criteria

  • Patient with major neurocognitive disorder diagnosed (dementia syndrome)
  • Pregnant, laboring, or breastfeeding female patients
  • Patient deprived of liberty by judicial or administrative decision. Patient in psychiatric care under constraints may be included.
  • For patients accepting the lumbar punction: patients who are unable to control themselves and are likely to engage in physical or violent behavior.

Treatment and study plan

Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

Biological

the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin

Primary outcomes

  1. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Time frame: Up to 10 weeks

    Changes in Positive and Negative Syndrome Scale (PANSS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for Schizophrenia patients. The minimal score is 30. The maximal score is 210.

  2. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Time frame: Up to 10 weeks

    Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for depression. The minimal score is 0. The maximal score is 60.

  3. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Time frame: Up to 10 weeks

    Changes in Young Mania Rating Scale (YMRS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for bipolar troubles. The minimal score is 0. The maximal score is 60.

  4. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Time frame: Up to 10 weeks

    Changes in Obsessive-Compulsive Inventory-Revised (OCI-R) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0. The maximal score is 72.

  5. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Time frame: Up to 10 weeks

    Changes in Visual analogic scale for obsessive compulsive disorder (VAS-OCD) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0 mm. The maximal score is 100 mm.

  6. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Time frame: Up to 10 weeks

    Changes in Bush-Francis Catatonia Rating Scale (BFCRS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for catatonia. The minimal score is 0 mm. The maximal score is 69.

  7. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Time frame: Up to 10 weeks

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : White blood cells, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets in G/L

  8. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Time frame: Up to 10 weeks

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : C3, C4, fibrinogen in g/L.

  9. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Time frame: Up to 10 weeks

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : Vitamin B12, IL-1β, IL-6, IL-18 in pg/mL.

  10. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Time frame: Up to 10 weeks

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : Folate, Vitamin B1, B6, D, cortisol in nmol/L.

  11. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Time frame: Up to 10 weeks

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : TSH, prolactin in mUI/L

  12. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Time frame: Up to 10 weeks

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : CRPus, β2 microglobulin, C1q in mg/L.

  13. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Time frame: Up to 10 weeks

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : anti-TPO Ab, anti-TG Ab, CH50 in UI/mL.

Secondary outcomes

  1. Changes in CRPus from inclusion (V1) to Day 2 (V2)

    Time frame: From enrollment to Day 2

    Variation in CRPus between inclusion (V1) and Day 2 (V2) in mg/L.

  2. Changes in immunity markers from inclusion (V1) to Day 2 (V2)

    Time frame: From enrollment to Day 2

    Variation in IL-1β, IL-6, and IL-18 between inclusion (V1) and Day 2 (V2) in pg/mL.

  3. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Time frame: From enrollment to Day 2

    Changes in Bush-Francis Catatonia Rating Scale (BFCRS) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for catatonia. The minimal score is 0 mm. The maximal score is 69.

  4. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Time frame: From enrollment to Day 2

    Changes in Positive and Negative Syndrome Scale (PANSS) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for Schizophrenia patients. The minimal score is 30. The maximal score is 210.

  5. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Time frame: From enrollment to Day 2

    Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores between inclusion (V1) and day 2 (V2). The scale will be used to assess disease severity for depression. The minimal score is 0. The maximal score is 60.

  6. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Time frame: From enrollment to Day 2

    Changes in Young Mania Rating Scale (YMRS) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for bipolar troubles. The minimal score is 0. The maximal score is 60.

  7. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Time frame: From enrollment to Day 2

    Changes in Visual analogic scale for obsessive compulsive disorder (VAS-OCD) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0 mm. The maximal score is 100 mm.

  8. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Time frame: From enrollment to Day 2

    Changes in Obsessive-Compulsive Inventory-Revised (OCI-R) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0. The maximal score is 72.

  9. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Time frame: through study completion, an average of 2 years

    Changes in Positive and Negative Syndrome Scale (PANSS) scores between inclusion (V1) and the end of study EOS (M24). The scale will be used to assess disease severity for Schizophrenia patients. The minimal score is 30. The maximal score is 210.

  10. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Time frame: through study completion, an average of 2 years

    Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for depression. The minimal score is 0. The maximal score is 60.

  11. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Time frame: through study completion, an average of 2 years

    Variation in standardized clinical disease scale scores between inclusion (V1) and EOS (M24).

    Changes in Young Mania Rating Scale (YMRS) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for bipolar troubles. The minimal score is 0. The maximal score is 60.

  12. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Time frame: through study completion, an average of 2 years

    Changes in Obsessive-Compulsive Inventory-Revised (OCI-R) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0. The maximal score is 72.

  13. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Time frame: through study completion, an average of 2 years

    Variation in standardized clinical disease scale scores between inclusion (V1) and EOS (M24).

    Changes in Visual analogic scale for obsessive compulsive disorder (VAS-OCD) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0 mm. The maximal score is 100 mm.

  14. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Time frame: through study completion, an average of 2 years

    Changes in Bush-Francis Catatonia Rating Scale (BFCRS) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for catatonia. The minimal score is 0 mm. The maximal score is 69.

  15. Changes from inclusion (V1) to end of study (M24) in CBC components

    Time frame: through study completion, an average of 2 years

    Variation in Complete Blood Count components between inclusion (V1) and End Of Study (M24) : White blood cells, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets in G/L.

  16. Changes from inclusion (V1) to end of study (M24) in Folates, Vitamin B6, Vitamin B1, Vitamin D

    Time frame: through study completion, an average of 2 years

    Changes in biological parameters measured between inclusion (V1) and the End Of Study (M24). The dosages are : Folates, Vitamins B1, B6, D in nmol/L.

  17. Changes from inclusion (V1) to end of study (M24) in Vitamin B12

    Time frame: through study completion, an average of 2 years

    Changes in Vitamin B12 measured between inclusion (V1) and the End Of Study (M24) in pg/mL.

  18. Changes from inclusion (V1) to end of study (M24) in TSH, prolactin

    Time frame: through study completion, an average of 2 years

    Changes in biological parameters measured between inclusion (V1) and End Of Study (M24). The dosages are : TSH, prolactin in mUI/L

  19. Changes from inclusion (V1) to end of study (M24) in drug dosage

    Time frame: through study completion, an average of 2 years

    Variation in drug dosage between inclusion (V1) and End Of Study (M24). Unit could be different according to the drug.

  20. Changes from inclusion in levels of pro-inflammatory cytokines and other immune biomarkers in cerebrospinal fluid, skin biopsies and/or stool, at end of acute treatment (V3), 6-month follow-up (V4), 12-month follow-up (V5) and 24-month follow-up (V6)

    Time frame: At inclusion (V1), 10 weeks, 6 months-, 12 months- and 24 months after end of acute treatment

    Change in levels of pro-inflammatory cytokines and other immune biomarkers in other biological samples (cerebrospinal fluid (CSF), skin biopsies, stool) between inclusion (V1) , end of acute treatment (V3), 6-month follow-up (V4), 12-month follow-up (V5) and 24-month follow-up (V6). This will enable direct assessment of the efficacy of interventions on immune processes.

  21. Changes from inclusion (V1) in functional (Clinical Global Impression, CGI-S and CGI-I) scores to end of acute treatment (V3)

    Time frame: Up to 10 weeks

    Variation in Clinical Global Impression (CGI-S and CGI-I) questionnaire scores between inclusion (V1) and end of acute treatment (V3):

    • CGI-Severity (CGI-S) assess global disease severity. The Score min is 1 and Score max is 7.
    • CGI-Improvement (CGI-I) : assess the improvement or deterioration of the disease compared to initial state. The Score min is 1 (highly improved). The Score max is 7 (Highly deteriorated).

  22. Changes from inclusion (V1) in quality of life (by WHOQOL-BREF questionnaire) scores to end of acute treatment (V3)

    Time frame: Up to 10 weeks

    Variation in WHOQOL-BREF questionnaire scores between inclusion (V1) and end of acute treatment (V3). The minimum score is 16 and the maximum is 80. The higher the score, the better the perceived quality of life in the relevant area.

  23. Changes from inclusion in quality of life (by WHOQOL-BREF scores), to End Of Study (M24)

    Time frame: through study completion, an average of 2 years

    Variation in quality-of-life questionnaire scores (WHOQOL-BREF) between inclusion (V1) and End Of Study (M24). The minimal score is 16 and the maximal is 80. The higher the score, the better the perceived quality of life in the relevant area.

  24. Changes from inclusion in functional score (by Clinical Global Impression scale), to End Of Study (M24)

    Time frame: through study completion, an average of 2 years

    Variation in Clinical Global Impression (CGI-S and CGI-I) questionnaire scores between inclusion (V1) and end of study (M24):

    • CGI-Severity (CGI-S) assess global disease severity. The Score min is 1 and Score max is 7.
    • CGI-Improvement (CGI-I) : assess the improvement or deterioration of the disease compared to initial state. The Score min is 1 (highly improved). The Score max is 7 (Highly deteriorated).

  25. Number of side-effects (type, intensity, severity) in total population and by cohort between study inclusion (V1) and end of study (M24)

    Time frame: through study completion, an average of 2 years

    Side-effects (type, intensity, severity) in total population and by cohort between study inclusion and End Of Study (M24)

  26. Number and characteristics of biomarkers identified in the retrospectively and prospectively included populations

    Time frame: through study completion, an average of 2 years

    The number and characteristics of biomarkers identified in the retrospectively and prospectively included populations throughout the study

  27. Changes from inclusion (V1) in fibrinogen, C3, C4 to End Of Study (M24)

    Time frame: through study completion, an average of 2 years

    Changes in biological parameters measured between inclusion (V1) and the end of study (M24). The dosages are : C3, C4, fibrinogen in g/L.

  28. Changes from inclusion (V1) to End Of Study (M24) in IL-1β, IL-6, IL-18

    Time frame: through study completion, an average of 2 years

    Changes in biological parameters measured between inclusion (V1) and the End Of Study (M24). The dosages are : IL-1β, IL-6, IL-18 in pg/mL.

  29. Changes from inclusion (V1) to End Of Study (M24) in cortisol dosage

    Time frame: through study completion, an average of 2 years

    Changes in cortisol measured between inclusion (V1) and the end of study (M24) in nmol/L.

  30. Changes from inclusion (V1) to End Of Study (M24) in CRPus, β2 microglobulin, C1q

    Time frame: through study completion, an average of 2 years

    Changes in biological parameters measured between inclusion (V1) and End Of Study (M24). The dosages are : CRPus, β2 microglobulin, C1q in mg/L.

  31. Changes from inclusion (V1) to End Of Study (M24) in anti-TPO Ab, anti-TG Ab, CH50

    Time frame: through study completion, an average of 2 years

    Changes in biological parameters measured between inclusion (V1) and the End Of Study (M24). The dosages are : anti-Peroxidase Antibodies, anti-thyroglobulin Antibodies, Hemolytic Complement 50 in UI/mL.

  32. Changes from inclusion (V1) to End Of Study (M24) in anti-TRAK Ab

    Time frame: through study completion, an average of 2 years

    Variation in anti TSH receptor specific Antibodies (anti-TRAK Ab) between inclusion (V1) and End Of Study (M24)

  33. Changes from inclusion (V1) to End Of Study (M24) in neuronal Ab

    Time frame: through study completion, an average of 2 years

    Number of positive neuronal antibodies between inclusion (V1) and End Of Study (M24)

  34. Changes from inclusion (V1) to End Of Study (M24) in interferon signature score

    Time frame: through study completion, an average of 2 years

    Variation in interferon signature score between inclusion (V1) and End Of Study (M24)

Study contacts

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

Iolanda PALIMARU, MD

CONTACT

[email protected]

+33145658798

Sponsors and collaborators

Lead sponsor

Centre Hospitalier St Anne

Other

Collaborators

  • GHU Paris Psychiatry & Neurosciences

Registry information

Acronym: BIO-INM

Important dates

Study start
2026
Primary completion
2036
Study completion
2038
First posted
Aug 3, 2026
Registry last updated
Aug 3, 2026

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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