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NCT Number: NCT06989944

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.

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Key information

Conditions

Major Depressive Disorder (MDD) Behavior Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders Motor Activity

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

IRCCS Centro San Giovanni fi Dio Fatebenefratelli, Brescia, Italy

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

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

Treatment and study plan

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

Primary outcomes

  1. Montgomery-Åsberg Depression Rating Scale (MADRS)

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

    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.

  2. Beck Depression Inventory - II

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

    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.

  3. Zung Self-Rating Depression Scale

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

    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

  4. Personal and Social Performance Scale

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

    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.

  5. World Health Organization Quality of Life - Bref

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

    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.

Secondary outcomes

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

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

    Electroencephalogram (EEG) recordings will be used to derive (a) Individual spectral analysis (theta/alpha transition frequency and individual alpha frequency); (b) Analysis of coherence; c) EEG source localisation with low resolution brain electromagnetic tomograghy; d) Analysis of connectivity.

  2. Metabolic analyses

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

    Plasma/serum levels of glucose and lipid metabolism markers

  3. Motor activity and circadian/sleep profiles

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

    Total activity count for every active minute throughout the day wearing an Actigraph accelerometer.

  4. Differentially Expressed genes and biological pathways modulation

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

  5. DNA Methylation

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

Sponsors and collaborators

Lead sponsor

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Other

Collaborators

  • Azienda Sanitaria Locale di Pescara
  • IRCCS San Raffaele
  • Istituto Neurologico Mediterraneo Neuromed S. R. L

Registry information

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
May 25, 2025
Registry last updated
Mar 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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