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RecruitingNCT07009223POWERUpdated Feb 11, 2026

Lifestyle Interventions to Prevent Cognitive Deficits in Subjects With Depressive Symptoms: From Mechanisms to Clinical Practice

An interventional study of Mediterranean Diet and Physical Activity in Major Depressive Disorder (MDD), Physical Activity and Inflammation, sponsored by IRCCS Centro San Giovanni di Dio Fatebenefratelli. Recruiting at 1 site in Italy. Open to participants aged 50 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-02-11.

Sponsored by IRCCS Centro San Giovanni di Dio Fatebenefratelli · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
50 Years to 80 Years
Sex
All
01

Study summary

The goal of this clinical study is to investigate if lifestyle changes can help prevent cognitive decline and reduce depressive symptoms in people between the ages of 50 and 80 with depressive symptoms or a diagnosis of major depression, but without signs of cognitive decline.

The main questions it aims to answer are:

  • Does regular physical activity improve mood and memory in people who are depressed or have depressive symptoms?
  • Does cognitive training help prevent mental difficulties in people at risk of cognitive decline?
  • Do changes in diet and lifestyle alter the composition of the gut microbiota and immuno-related infiammatory factors?

Researchers will compare three different treatment groups to see which intervention is most effective in improving mental and cognitive health.

The participants:

  • Will take part to online sessions on healthy eating based on the Mediterranean diet
  • Some will do regular exercise, supervised by a personal trainer
  • Others will do weekly cognitive training in small groups at the hospital
  • They will provide blood and fecal samples and complete cognitive tests and clinical questionnaires at the beginning, at the end of the treatment (12 weeks), and after 3 months.
02

Conditions studied

  • Major Depressive Disorder (MDD)
  • Physical Activity
  • Inflammation
  • Metabolome
  • Gut Microbiota
  • Depressive Symptoms

Keywords

  • Depression
  • Cognition
  • nutrition
03

Who can participate

Ages eligible
50 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Aged between 50 and 80 years;
  • Diagnosis of DDM according to DSM-5 or depressive symptoms (PHQ-9 or GDS-15 ≥ 5, the choice of test will be justified by the participant's age);
  • Ability to provide written informed consent.

Exclusion criteria

Exclusion Criteria:

  • Active gastrointestinal disorders;
  • Autoimmune disorders;
  • Chronic inflammatory disorders;
  • Diagnosis of dementia; cognitive impairment or mild functional impairment.
  • Use of antibiotics and/or anti-inflammatory drugs in the 8 weeks prior to the screening visit.
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Investigator, Outcomes assessor)
Enrollment
120 participants (estimated)

Study arms

  • Active comparator
    Group 1: Control group (CON)

    Behavioral: Mediterranean Diet

  • Experimental
    Group 2: CON + physical activity

    Behavioral: Mediterranean Diet · Behavioral: Physical Activity

  • Experimental
    Group 3: CON + Cognitive training

    Behavioral: Mediterranean Diet · Behavioral: Cognitive Training

Interventions

  • BehavioralMediterranean Diet

    Participants will receive only the educational intervention about the Mediterranean diet. The program consists of 4-5 online sessions conducted by a nutritionist.

  • BehavioralPhysical Activity

    In addition to educational sessions on the Mediterranean diet, there will be 2-3 weekly personalized exercise sessions, followed by a dedicated personal trainer at a partner gym. The treatment will last 12 weeks.

  • BehavioralCognitive Training

    In addition to educational sessions on the Mediterranean diet, there will be one weekly cognitive training session in groups, supervised by qualified staff at the IRCCS FBF. The treatment will last for 12 weeks.

05

What researchers measure

Primary outcomes

  1. MADR Scale for Depression

    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.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  2. PHQ-9

    The Patient Health Questionnaire-9 (PHQ-9) is a self-administered instrument used to assess the severity of depressive symptoms based on DSM criteria. It consists of 9 items, each rated from 0 (not at all) to 3 (nearly every day), resulting in a total score ranging from 0 to 27. Higher scores reflect more severe depressive symptoms, indicating a worse clinical outcome.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  3. GDS-15

    The Geriatric Depression Scale - Short Form (GDS-15) is a self-report questionnaire designed to screen for depressive symptoms in older adults. It contains 15 yes/no items, with a total score ranging from 0 to 15. Higher scores indicate more severe depressive symptoms, representing a worse clinical outcome.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  4. WHOQOL-BREF

    The World Health Organization Quality of Life - Bref (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.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  5. RBANS

    The Repeatable Battery for the Assessment of Neuropsychological (RBANS) is a neuropsychological battery composed of 12 subtests grouped into five domains: Immediate Memory, Visuospatial/Constructional, Language, Attention, and Delayed Memory. It yields index scores and a total scale score. Higher scores indicate better cognitive functioning, reflecting a more favorable clinical outcome.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  6. TMT

    The Trail Making Test (TMT) evaluates processing speed (Part A) and executive function, including task switching (Part B). The outcome is the time (in seconds) required to complete each part. Lower completion times indicate better performance and cognitive flexibility.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  7. DSST

    The Digit Symbol Substitution Test (DSST) evaluates attention, processing speed, and working memory. Participants match numbers and symbols in a limited time. Higher scores reflect better performance.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  8. M-WCST

    The Modified Wisconsin Card Sorting (M-WCST) measures cognitive flexibility and executive function. Outcomes include number of categories completed and perseverative errors. More categories and fewer errors indicate better performance.

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

Secondary outcomes

  1. Immunitary-related factors levels

    Plasma/serum levels of cytokines

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

  2. Gut Microbiome Composition

    Time frame: Baseline, Week 12, and 3-month follow-up (Week 24)

06

Study locations

1 of 1 sites recruiting
  • IRCCS Centro San Giovanni di Dio Fatebenefratelli
    Brescia, 25125, Italy
    Recruiting
07

Registry details

Key details

Study ID
NCT07009223
Lead sponsor
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Collaborators
Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC), University of Milan, China Medical University, China, University College Cork, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Responsible party
Sponsor
First posted
Jun 6, 2025
Start date
Oct 1, 2025
Primary completion
Aug 2026 (estimated)
Completion
Mar 2028 (estimated)
Last update
Feb 11, 2026

Study contacts

Elisa Mombelli
Contact
emombelli@fatebenefratelli.eu
(+39) 030 35 01 598
Moira Marizzoni, PhD
Contact
mmarizzoni@fatebenefratelli.eu
(+39) 030 35 01 563

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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