An observational study in Major Depressive Disorder (MDD), sponsored by IRCCS San Raffaele. Not yet recruiting. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-11-12.
Sponsored by IRCCS San Raffaele · Observational
Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and many patients do not respond adequately to available treatments. Plasticity, the ability of the brain and mind to change, is thought to be a crucial process in the transition from depression to wellbeing, but methods to measure it are limited. The Network Theory of Plasticity proposes that the weaker the connections among the elements of a system (for example, the symptoms of a patient or the regions of the brain), the higher its plasticity. Earlier analyses of large clinical datasets (STAR*D and CO-MED) supported this idea at the population level.
PlastNet is an observational study that aims to validate this approach at the individual level. Two hundred adults (18-70 years) with nonpsychotic MDD recruited at IRCCS Ospedale San Raffaele will undergo resting-state brain MRI, blood sampling and clinical assessments at baseline, and clinical assessments again after four weeks. No treatment is assigned by the study.
The investigators hypothesize that lower baseline functional connectivity in the brain is associated with a greater reduction in depressive symptoms over four weeks. The study will also investigate whether blood-based multi-omic profiles (genomic, transcriptomic and metabolomic) can identify biological signatures of plasticity. The results could help clinicians tailor treatments to each patient's level of plasticity.
Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Despite available treatments, a substantial proportion of patients do not respond adequately, which highlights the need for approaches that personalize therapeutic strategies.
Plasticity is defined as the ability to modify brain functioning, behaviors and mental states, and is increasingly recognized as a crucial process underlying the transition from psychopathology to wellbeing. Plasticity is neither inherently beneficial nor detrimental: enhanced plasticity increases the likelihood of a mental state transition without determining the direction of the transition, which is modulated by contextual factors such as quality of life. Treatments that enhance plasticity may therefore produce highly context-dependent effects. Lifestyle, environmental and psychotherapeutic interventions are also essential for promoting mental health, but not all individuals benefit equally, partly because of differences in individual plasticity levels. While psychometric tools to evaluate contextual factors have long been available, methods to operationalize and assess plasticity remain limited.
The Network Theory of Plasticity operationalizes plasticity as the inverse of connectivity strength among a system's elements: the weaker the connectivity, the higher the plasticity. Analyses of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and Combining Medications to Enhance Depression Outcomes (CO-MED) datasets provided preliminary evidence supporting this operationalization at the population level and showed its high sensitivity. PlastNet aims to validate this approach at the individual level and to use it to develop personalized therapeutic strategies.
Study design: PlastNet is an observational study. No medicinal product or medical device is under investigation, and no intervention is assigned. The procedures (blood sampling, resting-state functional magnetic resonance imaging (fMRI), and clinical and neuropsychological assessments) are standard clinical and research tools, and no additional risk beyond routine clinical practice is anticipated. Two hundred adults with nonpsychotic MDD will be recruited at IRCCS Ospedale San Raffaele over 24 months and followed for 4 weeks each. At baseline, participants undergo resting-state fMRI, blood sampling and clinical assessments; clinical assessments are repeated at the four-week follow-up. Contextual factors are assessed with the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire (quality of life), the Schedule of Recent Experiences (SRE) and the Perceived Stress Scale (PSS) (psychosocial stress), and socioeconomic status.
Primary objective and analysis: to generalize the operationalization of plasticity to the level of the central nervous system. The investigators hypothesize that lower baseline brain functional connectivity strength, derived from resting-state fMRI, is associated with a greater reduction in depressive symptom severity, measured as change in the total score of the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to four-week follow-up. Whole-brain connectivity strength is the primary predictor; connectivity within the default mode network and the salience network is a secondary predictor. Change in the total score of the 13-item Beck Depression Inventory (BDI-13) is analyzed as a supportive endpoint. Because there is no co-primary endpoint, no multiplicity adjustment is required.
Secondary objective: to identify biological signatures of plasticity through integrated multi-omics analyses of peripheral blood collected at baseline. The investigators hypothesize that baseline multi-omics profiles predict individual plasticity and change in the HDRS-17 and BDI-13 total scores. Analyses include transcriptomic profiling of peripheral blood mononuclear cells by RNA sequencing (Illumina NovaSeq 6000), genomic analysis with the Illumina Infinium Global Screening Array-24 (>680,000 markers) and untargeted metabolomics by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Data will be integrated using elastic net, random forests and Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) to generate individualized plasticity scores. Predictive accuracy will be assessed by cross-validation (alpha = 0.05), with Benjamini-Hochberg false discovery rate (FDR) correction (FDR \< 0.05).
Exploratory objective: to integrate symptom-based, neuroimaging-based and multi-omics-based plasticity measures into a unified individualized plasticity score and to investigate its interplay with contextual factors in determining treatment outcomes. No formal hypothesis is pre-specified; analyses are hypothesis-generating, and results will be considered preliminary pending replication.
Clinical significance: if validated, this approach could allow clinicians to tailor interventions to individual plasticity profiles, improving the precision and outcomes of psychiatric care.
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 200 is above the median of 131 across 400 observational studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →IRCCS San Raffaele is the lead sponsor of 454 studies on the registry; 235 are open to participants now.
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The enrolled population will consist of 200 adult patients, aged 18-70 years, diagnosed with nonpsychotic MDD according to DSM-5 criteria, and scoring 14 or higher on the HDRS.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
OSR will recruit 200 people who meet all these inclusion criteria:
Exclusion Criteria
Considering the 200 MDD patients' sample OSR will recruit, an individual who meets any of the following criteria will be excluded from participation in this study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
200 adult outpatients and inpatients (aged 18-70 years) recruited at IRCCS Ospedale San Raffaele, Milan, with a DSM-5 diagnosis of nonpsychotic major depressive disorder (MDD) and a score of 14 or higher on the 17-item Hamilton Depression Rating Scale (HDRS). Exclusion criteria are bipolar disorder, schizophrenia, psychosis NOS, anorexia or bulimia nervosa, OBCD, medical conditions incompatible with the protocol, and pregnancy or breastfeeding. At baseline, participants undergo structural and resting-state functional MRI, clinical and cognitive assessments, and blood sampling for multi-omic analyses. Clinical and cognitive assessments are repeated at 4 weeks. No intervention is assigned by the study; participants continue their usual care.
Other: Clinical and cognitive assessments · Other: Multimodal MRI · Other: Blood sampling for multi-omic analyses
Standardized assessment of depressive symptom severity (17-item HDRS) and cognitive performance, together with the Quality of Life Questionnaire, the Schedule of Recent Experiences and the Perceived Stress Scale. Assessments are performed at baseline and repeated at the 4-week follow-up. Participants continue their usual care, and no treatment is assigned or modified by the study.
Structural and resting-state functional MRI (3T) performed at baseline to derive whole-brain and network-level functional connectivity (including the default mode and salience networks). Connectivity strength is used as an inverse measure of plasticity. This is an observational measurement only and is not used to assign or modify treatment.
Blood collection at enrollment for genomic, transcriptomic and metabolomic analyses, including inflammation-related pathways. Molecular data are integrated with neuroimaging and clinical data to identify biological signatures of plasticity. Sampling is performed for research purposes only and does not influence clinical management.
Change in Hamilton Depression Rating Scale (HDRS-17) total score from baseline to week 4
Depressive symptom severity is measured with the 17-item Hamilton Depression Rating Scale (HDRS-17), total score range 0 to 52, where higher scores indicate more severe depression (worse outcome). The outcome is the change in total score from baseline to week 4. Baseline whole-brain functional connectivity strength, derived from resting-state fMRI, is the predictor.
Time frame: Baseline to four-week follow-up
Change in Hamilton Depression Rating Scale (HDRS-17) total score from baseline to week 4, in relation to multi-omics-derived plasticity profiles
Depressive symptom severity is measured with the 17-item Hamilton Depression Rating Scale (HDRS-17), with a total score range of 0 to 52, where higher scores indicate more severe depression (worse outcome). The outcome is the change in total score from baseline to week 4. Multi-omics-derived plasticity profiles (genomic, transcriptomic and metabolomic data from peripheral blood collected at baseline) are the predictors.
Time frame: Baseline to four-week follow-up
Change in Beck Depression Inventory-13 (BDI-13) total score from baseline to week 4, in relation to multi-omics-derived plasticity profiles
Depressive symptoms are measured with the Beck Depression Inventory-13 (BDI-13), a 13-item self-report questionnaire with a total score range of 0 to 39, where higher scores indicate more severe depression (worse outcome). The outcome is the change in total score from baseline to week 4. Multi-omics-derived plasticity profiles (genomic, transcriptomic and metabolomic data from peripheral blood collected at baseline) are the predictors.
Time frame: Baseline to four-week follow-up
Integrated individualized plasticity score
Individualized plasticity score integrating symptom-based, neuroimaging-based and multi-omics-based measures, and its association with change in the total scores of the 17-item Hamilton Depression Rating Scale (HDRS-17) and the 13-item Beck Depression Inventory (BDI-13), and with contextual factors at baseline: quality of life (World Health Organization Quality of Life-BREF, WHOQOL-BREF), psychosocial stress (Schedule of Recent Experiences, SRE, and Perceived Stress Scale, PSS) and socioeconomic status.
Time frame: Baseline to four-week follow-up
No study locations are listed for this record.
Plan to share: Yes
No publications or documents are linked to this record.
Start is estimated for Nov 2026; primary completion for Dec 2028, 25 months later.
Of 121 non-industry observational studies under Depressive Disorder, Major, half reached primary completion within 46 months of starting (the median), counting those still running; a quarter within 29 and three quarters within 73. This study's planned 25 months is below that.
Counting every sponsor, half of 150 studies reached it within 38 months; a quarter within 21 and three quarters within 67.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Nov 2026. You cannot join it, but the record below documents what was studied.
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