Immune Activation, Neural Plasticity and Depression

Recruiting

• Conditions: Mood Disorders; Sleep Deprivation; Major Depressive Disorder
• Interventions: Other: Total sleep deprivation

• Registration Number: NCT06306248
• Lead Sponsor: IRCCS San Raffaele

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.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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-03
• Study First Submitted: 2024-02-27
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-05
• Last Update Submitted: 2024-03-05
• Study First Posted: 2024-03-12
• Last Update Posted: 2024-03-12
• Primary Completion: 2025-03-03
• Study Completion: 2025-05-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MDD patients	Total sleep deprivation	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.

Primary Outcome Measures

Name	Time	Method
BENEFICIAL EFFECT OF total sleep deprivation in inflamed vs non inflamed patients.	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.

Secondary Outcome Measures

Name	Time	Method
Neurobiological markers of prediction and progression of antidepressant treatment	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).

Trial Locations

Locations (1)

IRCCS Ospedale San Raffaele; 🇮🇹 Milan, Mi, Italy