Immune Activation, Neural Plasticity and Depression

NCT ID: NCT06306248

Last Updated: 2024-03-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-03-03

Study Completion Date

2025-05-09

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Mood Disorders Major Depressive Disorder Sleep Deprivation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Total sleep deprivation

Intervention Type OTHER

non pharmacologic treatment for depression

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Total sleep deprivation

non pharmacologic treatment for depression

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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;
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

IRCCS San Raffaele

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Sara Poletti

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Sara Poletti, PhD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Ospedale San Raffaele

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

IRCCS Ospedale San Raffaele

Milan, Mi, Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Sara Poletti, phd

Role: CONTACT

+390226433156

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Sara SP Poletti, phd

Role: primary

390226433156

References

Explore related publications, articles, or registry entries linked to this study.

Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006 Jan;163(1):28-40. doi: 10.1176/appi.ajp.163.1.28.

Reference Type BACKGROUND
PMID: 16390886 (View on PubMed)

Benedetti F, Dallaspezia S, Melloni EMT, Lorenzi C, Zanardi R, Barbini B, Colombo C. Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1beta:IL-1ra Ratio in Bipolar Depression. Front Physiol. 2021 Sep 1;12:740686. doi: 10.3389/fphys.2021.740686. eCollection 2021.

Reference Type BACKGROUND
PMID: 34539454 (View on PubMed)

Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016 Jan;16(1):22-34. doi: 10.1038/nri.2015.5.

Reference Type BACKGROUND
PMID: 26711676 (View on PubMed)

Leboyer M, Berk M, Yolken RH, Tamouza R, Kupfer D, Groc L. Immuno-psychiatry: an agenda for clinical practice and innovative research. BMC Med. 2016 Oct 28;14(1):173. doi: 10.1186/s12916-016-0712-5.

Reference Type BACKGROUND
PMID: 27788673 (View on PubMed)

Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry. 2009 Sep 1;66(5):407-14. doi: 10.1016/j.biopsych.2009.03.015. Epub 2009 May 7.

Reference Type BACKGROUND
PMID: 19423079 (View on PubMed)

Hepgul N, Cattaneo A, Agarwal K, Baraldi S, Borsini A, Bufalino C, Forton DM, Mondelli V, Nikkheslat N, Lopizzo N, Riva MA, Russell A, Hotopf M, Pariante CM. Transcriptomics in Interferon-alpha-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression. Neuropsychopharmacology. 2016 Sep;41(10):2502-11. doi: 10.1038/npp.2016.50. Epub 2016 Apr 12.

Reference Type BACKGROUND
PMID: 27067128 (View on PubMed)

Carvalho LA, Torre JP, Papadopoulos AS, Poon L, Juruena MF, Markopoulou K, Cleare AJ, Pariante CM. Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J Affect Disord. 2013 May 15;148(1):136-40. doi: 10.1016/j.jad.2012.10.036. Epub 2012 Nov 27.

Reference Type BACKGROUND
PMID: 23200297 (View on PubMed)

Branchi I, Poggini S, Capuron L, Benedetti F, Poletti S, Tamouza R, Drexhage HA, Penninx BWJH, Pariante CM; European College of Neuropsychopharmacology (ECNP) ImmunoNeuroPsychiatry Thematic Working Group and Marion Leboyer. Brain-immune crosstalk in the treatment of major depressive disorder. Eur Neuropsychopharmacol. 2021 Apr;45:89-107. doi: 10.1016/j.euroneuro.2020.11.016. Epub 2020 Dec 29.

Reference Type BACKGROUND
PMID: 33386229 (View on PubMed)

Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry. 2009 Jan;22(1):32-6. doi: 10.1097/YCO.0b013e328315a561.

Reference Type BACKGROUND
PMID: 19122532 (View on PubMed)

Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, Mohr DC, Schatzberg AF. Major depressive disorder. Nat Rev Dis Primers. 2016 Sep 15;2:16065. doi: 10.1038/nrdp.2016.65.

Reference Type BACKGROUND
PMID: 27629598 (View on PubMed)

Kohler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, Krogh J. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2014 Dec 1;71(12):1381-91. doi: 10.1001/jamapsychiatry.2014.1611.

Reference Type BACKGROUND
PMID: 25322082 (View on PubMed)

Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006 Jul;11(7):680-4. doi: 10.1038/sj.mp.4001805. Epub 2006 Feb 21.

Reference Type BACKGROUND
PMID: 16491133 (View on PubMed)

Wittenberg GM, Stylianou A, Zhang Y, Sun Y, Gupta A, Jagannatha PS, Wang D, Hsu B, Curran ME, Khan S; MRC ImmunoPsychiatry Consortium; Chen G, Bullmore ET, Drevets WC. Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders. Mol Psychiatry. 2020 Jun;25(6):1275-1285. doi: 10.1038/s41380-019-0471-8. Epub 2019 Aug 19.

Reference Type BACKGROUND
PMID: 31427751 (View on PubMed)

Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9262-7. doi: 10.1073/pnas.1104836108. Epub 2011 Apr 25.

Reference Type BACKGROUND
PMID: 21518864 (View on PubMed)

Dallaspezia S, Benedetti F. Chronobiological therapy for mood disorders. Expert Rev Neurother. 2011 Jul;11(7):961-70. doi: 10.1586/ern.11.61.

Reference Type BACKGROUND
PMID: 21721914 (View on PubMed)

WHO, 2008 The global burden of disease: 2004 update

Reference Type BACKGROUND

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PNRR-MAD-2022-12375716

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Cytokine-Associated Depression and Social Pain
NCT00949845 COMPLETED EARLY_PHASE1