Inflammatory Control of Antidepressant Efficacy: a Pharmaco-epigenetic Approach

NCT ID: NCT06306209

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-05-18
• Study Completion Date: 2025-01-14

Brief Summary

Major depressive disorder (MDD) is a chronic, recurring and potentially life-threatening illness that affects up to 10% of the population across the globe.It posits that the increase in serotonin levels induced by Selective Serotonin Reuptake Inhibitors (SSRIs) does not affect mood per se, but enhances brain plasticity and thus amplifies the influence of the environment on the individual. Thus, SSRI treatment has not a univocal effect but, in a favorable environment, it would lead to a reduction of symptoms while in a stressful environment might lead to a worse prognosis.Such innovative view opens new perspectives on how to improve SSRI efficacy by controlling the environment. However, often it is not possible to act on the quality of the living environment because of constraints due to patient's personal history and unchangeable life circumstances. In these cases, the pharmacological modulation of the factors underlying the link between living environment and SSRI efficacy represents a novel and desirable strategy to improve treatment outcome even in patients living in adverse conditions, which are very common in depressed patients. Inflammatory levels are markedly affected by the socioeconomic status and thus by the quality of the living environment. The hypothesis of the present project is that inflammation mediates the influence of the environment on SSRI outcome.Therefore, the control of inflammatory levels is a promising strategy to improve treatment efficacy and overcome the limited SSRI efficacy, especially when administered in patients living in adverse conditions. A further hypothesis is that the influence of the environment on inflammation, in turn affecting SSRI efficacy, occurs through epigenetic modifications. Therefore, the project aims at developing a pharmaco-epigenetic approach as effective treatment for MDD. In addition, through neuroimaging investigations, it will provide important information about functional and structural brain modifications associated to SSRI efficacy in patients.

Both males and females will be considered because MDD is twice as common in women than men, suggesting that different mechanisms may underlie the psychopathology in the two sexes.

Conditions

Mood Disorders; Major Depressive Disorder

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

MDD

80 patients with a depressive episode in course of major depression (MDD) and treated with SSRI's will be studied. The study does not include the evaluation of pharmacological treatments. The treatments will be administered in the judgment of the attending physician, independently of the experimental protocol.

Treatment as usual (TAU), i.e., pharmacotherapy plus clinical management

Intervention Type: OTHER

All participants enrolled in the study will receive Treatment as usual (TAU), i.e., pharmacotherapy plus clinical management. Clinicians will be free to choose antidepressant medication, doses and drug combinations, including augmentations strategies and non-pharmacological treatments, which will follow standard clinical treatment guidelines for MDD.

Interventions

Treatment as usual (TAU), i.e., pharmacotherapy plus clinical management

All participants enrolled in the study will receive Treatment as usual (TAU), i.e., pharmacotherapy plus clinical management. Clinicians will be free to choose antidepressant medication, doses and drug combinations, including augmentations strategies and non-pharmacological treatments, which will follow standard clinical treatment guidelines for MDD.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

A depressive episode according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria in the course of MDD with:

HDRS score > 17 Age 18-65 years; In treatment with SSRIs Signed informed consent, able to understand, speak and write the national language

Exclusion Criteria

• History of bipolar disorder, schizophrenia, schizoaffective disorder, psychosis not otherwise specified; anorexia or bulimia nervosa;
• Taking following medications: antipsychotics, anticonvulsants, mood stabilizers; stimulants
• Active infection requiring antibiotics therapy;
• Immunosuppressed patient
• Other chronic diseases
• Signs of active infection requiring treatment
• Use of anti-inflammatory medication on a regular basis for a chronic inflammatory/autoimmune Disorder.
• Forbidden treatment: corticosteroids, Non Steroidal Anti-inflammatory Drugs, immunosuppressant IV-Ig based treatment
• Ongoing fever, infection treated by antibiotics or uncontrolled diabetes type I or II;
• Existing cancer or history of cancer in the last 5 years (except skin epidermoid cancer or in-situ cervix cancer);
• Known HIV infection or clinically manifest Acquired Immune Deficiency Syndrome (AIDS),
• Parkinson's or Alzheimer's disease, or any other serious condition likely to interfere e with the conduct of the trial;
• Abuse of drugs or alcohol in the past 6 months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Sara Poletti

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

sara Poletti, PhD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Ospedale San Raffaele

Locations

IRCCS Ospedale San Raffaele

Milan, Mi, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Sara Poletti, phd

Role: CONTACT

poletti.sara@hsr.it

+390226433156

Facility Contacts

Sara sp Poletti, phd

Role: primary

poletti.sara@hsr.it

+390226433156

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Other Identifiers

DeFLAME

Identifier Type: -

Identifier Source: org_study_id