How exercise affects the brain and inflammation in depression

Inflammatory and Brain Mechanisms and Clinical and Cognitive Effects of an Exercise Intervention in Major Depressive Disorder: a Randomised Longitudinal Clinical Trial.

Not applicable Interventional Fundación de Investigación Biomédica - Hospital Universitario de La Princesa · NCT06450704

This project tests whether adding a structured exercise program to standard antidepressant treatment helps people with moderate major depressive disorder and whether it reduces inflammation and changes brain markers.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment124 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorFundación de Investigación Biomédica - Hospital Universitario de La Princesa Academic / other
Locations5 sites (Alcalá de Henares, Madrid and 4 other locations)
Trial IDNCT06450704 on ClinicalTrials.gov

What this trial studies

Outpatients with moderate Major Depressive Disorder who are on stable antidepressant medication will be assigned to either a 12-week structured physical exercise program added to their usual care or to continue usual care without changing activity. Depressive symptoms will be measured with the HAM-D17, while blood samples will be taken to measure inflammatory and oxidative stress markers and MRI scans will probe brain structure and function before and after the intervention. The study aims to connect clinical changes in mood with shifts in inflammatory signaling, oxidative stress, and neuroimaging findings to clarify mechanisms. The exercise program is delivered in routine outpatient settings to test both effectiveness and real-world feasibility as an add-on to pharmacologic treatment.

Who should consider this trial

Good fit: Adults with a DSM-5 diagnosis of Major Depressive Disorder, outpatient care, HAM-D17 score of at least 14, on a stable antidepressant regimen, able to undergo MRI and participate in exercise.

Not a fit: People who are pregnant, have other axis I diagnoses, recent antiinflammatory treatment or vaccines, fever, MRI contraindications, substance abuse, or who cannot safely perform exercise are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could reduce depressive symptoms as an affordable add-on to medication and identify biological markers that explain who benefits most.

How similar studies have performed: Previous trials have shown that exercise can improve mild-to-moderate depression, but mechanistic links to inflammation and brain imaging remain under-studied and are the novel focus here.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* A diagnosis of Major Depressive Disorder (MDD) according to DSM-5 criteria (through the Mini International Neuropsychiatric Interview (MINI)
* Severity of depression according to the Hamilton Depression Rating Scale 17 items (HAM-D17): minimum of 14 cut-off score of moderate depression.
* Outpatient clinical care.
* Current antidepressant treatment that will be maintained during the 12 weeks of the physical exercise intervention.

Exclusion Criteria:

* Diagnosis of any axis I diagnosis except for MDD;
* Contraindications for Magnetic Resonance Imaging.
* Antiinflammatory treatments or antibiotics within the week before randomisation.
* Vaccines within the month before randomisation.
* Fever (\>38ºC) at the moment of study entry.
* Pregnant women.
* Alcohol or drug abuse.

Where this trial is running

Alcalá de Henares, Madrid and 4 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Major Depressive DisorderInflammatory ResponsePhysical ExerciseInflammationNeuroimaging
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.