Major Depressive Disorder (MDD)NCT06989944
Physical Activity-based Intervention in Depressed Patients: Clinical, Neurophysiological, Epigenetic and Metabolic Correlates
A study testing Physical Activity (PA) program in people with Major Depressive Disorder (MDD), run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 4 sites in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- Physical Activity (PA) program
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 4 sitesItaly
- Study dates
- 1 May 2025to 1 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Severe psychopathology
- Medical contraindications to PA (PAR-Q)
- Orthopedic problems/diseases which limit physical fitness assessment
- Currently pregnant (or planning to become pregnant)
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
IRCCS Centro San Giovanni fi Dio Fatebenefratelli
Brescia, 25125
Istituto Neurologico Mediterraneo Neuromed, NEUROMED
Isernia, 86077
IRCCS Ospedale San Raffaele
Milan, 20132
Azienda Sanitaria Locale di Pescara
Pescara, 65124
About this study
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?
Read more
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)
- Being tested
- Physical Activity (PA) program
- Keywords
- Major depressive disorder, physical activity
- Medical subject headings
- Depressive Disorder, Major, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physical Activity (PA) programBehavioural
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Behavioral: Physical Activity (PA) program |
| Control-arm | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: Baseline (Day 1); Month 3 (up to 3 months; end of treatment); Month 6 (up to 6 months, follow - up)
Metabolic analyses
Plasma/serum levels of glucose and lipid metabolism markers
Measured: Baseline (Day 1); Month 3 (up to 3 months; end of treatment)
Motor activity and circadian/sleep profiles
Total activity count for every active minute throughout the day wearing an Actigraph accelerometer.
Measured: 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
Measured: Baseline (Day 1); Month 3 (up to 3 months; end of treatment)
DNA Methylation
Measured: Baseline (Day 1); Month 3 (up to 3 months; end of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2025
- Study start1 May 2025
- Primary completion1 Aug 2026
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two-arm randomized controlled design
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Centro San Giovanni di Dio Fatebenefratelli
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS San Raffaele, Istituto Neurologico Mediterraneo Neuromed S. R. L, Azienda Sanitaria Locale di Pescara
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06989944
- Sponsor's protocol ID
- PNRR-MCNT2-2023-12377777
- Status last verified
- Oct 2026
- First submitted
- 29 Apr 2025
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data generated by the trial will be made available, where legally and ethically permissible, through a suitable controlled-access data repository. Access will be subject to authentication and approval by the study investigators or their delegate, based on the scientific rationale of the request and in accordance with participants' consent, GDPR requirements, and applicable institutional and ethical regulations. Data underlying the results reported in publications arising from the trial may also be made available upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physical Activity-based Intervention in Depressed Patients: Clinical, Neurophysiological, Epigenetic and Metabolic Correlates
- ClinicalTrials.gov ID
- NCT06989944
- Acronym / sponsor ID
- PNRR-MCNT2-2023-12377777
- Conditions
- Major Depressive Disorder (MDD)
- Keywords
- Major depressive disorder, physical activity
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- IRCCS Centro San Giovanni di Dio FatebenefratelliUniversity, hospital or other
- Collaborators
- IRCCS San Raffaele, Istituto Neurologico Mediterraneo Neuromed S. R. L, Azienda Sanitaria Locale di Pescara
- Study start
- 1 May 2025 (actual)
- Primary completion
- 1 Aug 2026 (actual)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 25 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Two-arm randomized controlled design
| Arm | Type | Receives |
|---|---|---|
| PA-arm | Experimental | Behavioral: Physical Activity (PA) programParticipants assigned to the PA-arm will participate in at least three weekly 30-minute sessions of PA for a total of 12 weeks. |
| Control-arm | No intervention | –No intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- Severe psychopathology
- Medical contraindications to PA (PAR-Q)
- Orthopedic problems/diseases which limit physical fitness assessment
- Currently pregnant (or planning to become pregnant)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Physical Activity (PA) programParticipants 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 | Behavioural | PA-arm |
Primary outcome
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.
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.
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
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.
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.
5 secondary outcomes
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)
Metabolic analyses
Time frame: Baseline (Day 1); Month 3 (up to 3 months; end of treatment)
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)
Differentially Expressed genes and biological pathways modulation
Time frame: Baseline (Day 1); Month 3 (up to 3 months; end of treatment)
DNA Methylation
Time frame: Baseline (Day 1); Month 3 (up to 3 months; end of treatment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data generated by the trial will be made available, where legally and ethically permissible, through a suitable controlled-access data repository. Access will be subject to authentication and approval by the study investigators or their delegate, based on the scientific rationale of the request and in accordance with participants' consent, GDPR requirements, and applicable institutional and ethical regulations. Data underlying the results reported in publications arising from the trial may also be made available upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Physical Activity (PA) program in people with Major Depressive Disorder (MDD), run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 4 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.