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

NCT06989944 | Active Not Recruiting

• 1 other identifier: PNRR-MCNT2-2023-12377777
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Major Depressive Disorder (MDD)

Keywords

Major depressive disorder; physical activity

Outcome Measures

Primary Outcomes (5)

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-administered scale designed to assess the severity of depressive symptoms. It consists of 10 items, each rated on a scale from 0 to 6, yielding a total score ranging from 0 to 60. Higher scores indicate greater severity of depression, meaning a worse clinical outcome.

  Baseline (day one), Month 3 (up to three months; end of treatment), Month 6 (up to 6 months; follow up).

• Beck Depression Inventory - II

  The Beck Depression Inventory (BDI) is a self-report questionnaire used to assess the presence and severity of depressive symptoms. It comprises 21 items, each rated on a scale from 0 to 3, resulting in a total score ranging from 0 to 63. Higher scores reflect more severe depressive symptoms, indicating a worse clinical outcome.

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment); Month 6 (up to 6 months, follow - up)

• Zung Self-Rating Depression Scale

  The Zung Self-Rating Depression Scale (ZDS) is a self-administered questionnaire designed to assess the level of depressive symptoms in individuals. It consists of 20 items, each rated on a scale from 1 to 4, based on how often symptoms are experienced. The raw total score ranges from 20 to 80, which is often converted to an index score (ranging from 25 to 100) by multiplying the raw score by 1.25. Higher scores indicate more severe depression

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment); Month 6 (up to 6 months, follow - up)

• Personal and Social Performance Scale

  The Personal and Social Performance Scale (PSP) is a clinician-rated instrument used to assess personal and social functioning in individuals with mental disorders. The total score ranges from 1 to 100, with higher scores indicating better functioning and a more favorable clinical outcome.

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment); Month 6 (up to 6 months, follow - up)

• World Health Organization Quality of Life - Bref

  The WHOQOL-BREF is a self-report questionnaire developed by the WHO to assess quality of life across multiple domains. It contains 26 items rated on a 5-point Likert scale. Higher scores indicate a better quality of life, reflecting a more favorable outcome.

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment); Month 6 (up to 6 months, follow - up)

Secondary Outcomes (5)

• EEG-derived neurophysiological metrics, including spectral, coherence, source localization, and graph-based connectivity measures

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment); Month 6 (up to 6 months, follow - up)

• Metabolic analyses

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment)

• Motor activity and circadian/sleep profiles

  24h/day for 7 days before baseline, months 3 (at the end of the trial) and month 6 (up to 6 months follow up)

• Differentially Expressed genes and biological pathways modulation

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment)

• DNA Methylation

  Baseline (Day 1); Month 3 (up to 3 months; end of treatment)

Study Arms (2)

PA-arm

EXPERIMENTAL

Participants assigned to the PA-arm will participate in at least three weekly 30-minute sessions of PA for a total of 12 weeks.

Behavioral: Physical Activity (PA) program

Control-arm

NO INTERVENTION

No intervention

Interventions

Physical Activity (PA) program BEHAVIORAL

Participants assigned to the PA-arm will participate in at least three weekly 30-minute sessions of PA for a total of 12 weeks. The PA program will be tailored to individuals' characteristics, skills and preferences, based on information collected in connection with the baseline assessment and physical examination. A PA program could preview some forms of aerobic/relaxation/anaerobic exercises

PA-arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Primary diagnosis of depression (DSM-5 criteria)
• Symptoms of depression according to MADR, BDI, ZDR Scale
• Ability to provide written IC
• Self-reported moderate-intensity leisure PA\< 150 min/week

You may not qualify if:

• Severe psychopathology
• Medical contraindications to PA (PAR-Q)
• Orthopedic problems/diseases which limit physical fitness assessment
• Currently pregnant (or planning to become pregnant)

Sponsors & Collaborators

• IRCCS Centro San Giovanni di Dio Fatebenefratelli: lead
• IRCCS San Raffaele: collaborator
• Istituto Neurologico Mediterraneo Neuromed S. R. L: collaborator
• Azienda Sanitaria Locale di Pescara: collaborator

Study Sites (4)

IRCCS Centro San Giovanni fi Dio Fatebenefratelli

Brescia, 25125, Italy

Location

Istituto Neurologico Mediterraneo Neuromed, NEUROMED

Isernia, 86077, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Sanitaria Locale di Pescara

Pescara, 65124, Italy

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-arm randomized controlled design

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: May 25, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 25, 2026

Record last verified: 2026-02

Locations

IT (4)