Physical Activity-based Intervention in Depressed Patients: Clinical, Neurophysiological, Epigenetic and Metabolic Correlates

The goal of this clinical trial is to investigate the effect of a structured physical activity (PA) program on depressive symptomatology in adults with a diagnosis of major depression disorder (MDD). The study will evaluate changes in depressive symptoms and assess neurophysiological and biological modulations, including epigenetic, transcriptomic, and metabolic changes resulting from the PA intervention. The main questions it aims to answer are: * Does physical activity have an impact on depressive symptoms in patients affected by depression? * What are the neurophysiological, epigenetic, and metabolic mechanisms through which PA can modulate the intensity of depressive symptoms? Participants will be randomized into two arms: the intervention group (n total=55), in treatment with antidepressants, participating in a 12-weeks PA program; the control group (n total=55), patients in treatment with antidepressants, without receiving the PA program. All participants will be assessed at three-time points: T0 (baseline, before initiating the trial), T3 (after three months; at the end of the 12-week PA program), and T6 (6th-month follow up; three months after the PA completion). At each assessment, all participants will: * Complete clinical evaluation questionnaires * Provide blood samples * Undergo electroencephalogram (EEG) measurements. * Wear an actigraph 24 hours a day for 7 days before the initiation of the trial, at T3, and at T6.

NCT Number	NCT06989944
Lead Sponsor	IRCCS Centro San Giovanni di Dio Fatebenefratelli Collaborators: IRCCS San Raffaele, Istituto Neurologico Mediterraneo Neuromed S. R. L, Azienda Sanitaria Locale di Pescara
Conditions	Major Depressive Disorder (MDD)
Enrollment	110 participants
Start Date	2025-05-01
Primary Completion	2026-08-01 (estimated)
Study Completion	2027-02-01 (estimated)
Updated on ClinicalTrials.gov	2026-03-25