Clinical trial NCT06306209: Inflammatory Control of Antidepressant Efficacy: a Pharmaco-epigenetic Approach
Official title: Inflammatory Control of Antidepressant Efficacy: a Pharmaco-epigenetic Approach
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Mood Disorders
Major Depressive Disorder
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients are always informed on currently ongoing and upcoming (clinical) duties during their regular outpatient clinic visits and at the first interview during hospitalization

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.


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

Primary outcomes:
measure: The potential role of inflammation as the causal link between the quality of the environment and SSRI efficacy
timeFrame: Blood samples will be collected at baseline time and after 3 months in correspondence with routine blood sampling performed at the patients arrival in the hospital.
measure: interaction between early stress and recent stress on the response to treatment and the role of inflammation
timeFrame: at baseline, at 3 months follow up
measure: identification of neurobiological predictors of response to treatment
timeFrame: at baseline, at 3 months follow up
measure: identification of neurobiological predictors of response to treatment
timeFrame: at baseline, at 3 months follow up
measure: identification of neurobiological predictors of response to treatment
timeFrame: at baseline, at 3 months follow up, at 6 months follow up
Secondary outcomes:
measure: epigenetic changes in cytokine regulating genes which could mediate the effect of stress on response to treatment.
timeFrame: Blood samples will be collected at baseline time and after 3 months in correspondence with routine blood sampling performed at the patients arrival in the hospital.
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
state: Mi
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: sara Poletti, PhD
role: PRINCIPAL_INVESTIGATOR
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