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

NCT07741981 | Not Yet Recruiting

• 2 other identifiers: D25-P041N°ID-RCB: 2026-A00433-48
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia; Treatment Resistant Depression (TRD); Bipolar Disorder (BD); Catatonia; Obsessive Compulsive Disorder (OCD)

Keywords

biomarkers; treatment resistance; response prediction

Outcome Measures

Primary Outcomes (13)

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

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

  Up to 10 weeks

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

  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.

  Up to 10 weeks

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

  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.

  Up to 10 weeks

Secondary Outcomes (34)

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

  From enrollment to Day 2

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

  From enrollment to Day 2

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

  From enrollment to Day 2

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

  From enrollment to Day 2

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

  From enrollment to Day 2

Study Arms (5)

OCD cohort

OTHER

Patients suffering from OCD resistant to treatments

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

Catatonia cohort

OTHER

Patients suffering from resistant catatonia

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

TRD cohort

OTHER

Patients suffering from treatment resistant depression (TRD)

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

BD cohort

OTHER

Patients suffering from treatment resistant bipolar disorders (BD)

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

Schizophrenia cohort

OTHER

Patients suffering from schizophrenia resistant to treatments

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

Interventions

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

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

BD cohort; Catatonia cohort; OCD cohort; Schizophrenia cohort; TRD cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead
• GHU Paris Psychiatry & Neurosciences: collaborator

Study Sites (1)

GHU Paris - Psychiatrie et Neurosciences

Paris, 75014, France

Location

MeSH Terms

Conditions

Schizophrenia; Depressive Disorder, Treatment-Resistant; Bipolar Disorder; Catatonia; Obsessive-Compulsive Disorder

Interventions

Blood Specimen Collection; Spinal Puncture

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Bipolar and Related Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Anxiety Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Biopsy; Diagnostic Techniques, Neurological; Therapeutics

Study Officials

• Anne-Cécile PETIT, MD, PhD

  GHU Paris Psychiatry & Neurosciences

  STUDY DIRECTOR

Central Study Contacts

Iolanda PALIMARU, MD

CONTACT

+33145658798; iolanda.palimaru@ghu-paris.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-center, ambispective, non-randomized, non-controlled study. Exploratory study investigating biomarkers of treatment resistance in adult patients with psychiatric disorders. Patients will be divided into 5 cohorts.

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: August 3, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): October 1, 2036
• Study Completion (Estimated): August 1, 2038
• Last Updated: August 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)