Immune Activation, Neural Plasticity and Depression

March 5, 2024 updated by: Sara Poletti, IRCCS San Raffaele

Adjusting Immune Activation to Reinstate Neural Plasticity and Promote the Beneficial Effect of Non-pharmacological Interventions

Major depressive disorder (MDD) is a chronic, recurring and potentially life-threatening illness that affects up to 10% of the population across the globe.Increasing evidence indicates a clear link between immune dysfunction and MDD.Moreover, an activation of inflammatory pathways is associated to a lack of clinical response to antidepressants. Thus, the regulation of inflammation represents a potential approach to modulate the link between the living environment and antidepressant outcome. Light therapy combined with sleep deprivation hastens recovery, with benefits that can be perceived by patients during the first week of treatment. Alteration of the sleep-wake cycle and of sleep structure are core symptoms of MDD.The aims of the present project are (i) to show that neural plasticity and the environmental context are moderating factors of the therapeutic outcome of immune modulation and (ii) to exploit their interplay to set up novel and effective therapeutic strategies for MDD.This is a observational prospective study with non-invasive add-on procedures (Magnetic Resonance without contrast). In this study, 60 patients with a depressive episode in course of MDD and treated with a chronobiological intervention including total sleep deprivation (TSD) + light therapy (LT), as performed in clinical practice, will be studied. All participants enrolled in the study will receive Treatment As Usual (TAU), i.e., pharmacotherapy, chronobiological intervention plus clinical management. Drug prescription will be performed during the clinical management sessions.The study will have a total duration of 24 months. Each subject will participate in the study for 6 months, will undergo Magnetic Resonance Imaging (MRI) and clinical evaluation at baseline, after one week of chronobiological treatment and at 6 months follow-up.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Mi
      • Milan, Mi, Italy, 20132
        • Recruiting
        • IRCCS Ospedale San Raffaele
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with major depressive disorder

Description

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 TSD+LT
  • 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 or 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 Other exclusion criteria related to the MRI procedure include
  • Aneurysm clip
  • Implanted neural stimulator
  • Implanted cardiac pacemaker or auto-defibrillator
  • Cochlear implant
  • Ocular foreign body (e.g., metal shavings)
  • Any implanted device (pumps, infusion devices, etc)
  • Shrapnel injuries

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
MDD patients

60 patients with a depressive episode in course of major depression (MDD) and treated with a chronobiological intervention including total sleep deprivation (TSD) + light therapy (LT).

Each subject will participate in the study for 6 months, will undergo MRI and clinical evaluation that will take overall about 2 hours at baseline (V0), after one week of chronobiological treatment and at 6 month follow-up.
Other: Total sleep deprivation
non pharmacologic treatment for depression

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
BENEFICIAL EFFECT OF total sleep deprivation in inflamed vs non inflamed patients.
Time Frame: at baseline, 1 week follow-up, 6 months follow up
Response to total sleep deprivation will be measured (50% reduction in hamilton depression rating scale (HDRS), min score 0 max 52; higher scores higher severity of depression) in patients with C reactive protein levels <3 and >=3 mg/L.
at baseline, 1 week follow-up, 6 months follow up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurobiological markers of prediction and progression of antidepressant treatment
Time Frame: from baseline to 6 months follow up
a machine learning algorithm will be implemented to identify markers of prediction of response to treatment (50% reduction in HDRS, min score 0 max 52; higher scores higher severity of depression) and disease progression (number of relapses and severity of depression at 6 months follow-up) based on changes in peripheral inflammatory markers and in brain measures of neural plasticity (e.g. brain levels of glutamate and GABA; measures of resting state functional connectivity: amplitude of low-frequency fluctuation, regional homogeneity) and structural integrity (e.g. brain volumes, white matter microstructure - fractional anisotropy).
from baseline to 6 months follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Investigators

  • Principal Investigator: Sara Poletti, PhD, IRCCS Ospedale San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2023

Primary Completion (Estimated)

March 3, 2025

Study Completion (Estimated)

May 9, 2025

Study Registration Dates

First Submitted

February 27, 2024

First Submitted That Met QC Criteria

March 5, 2024

First Posted (Actual)

March 12, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PNRR-MAD-2022-12375716

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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