The goal of this clinical trial is to study how physical exercise works when applied to patients diagnosed with Major Depressive Disorder (MDD). The main questions it aims to answer are:
* What are the antiinflammatory and oxidative stress and neural mechanisms involved in the antidepressant effects of exercise? * How effective is a physical exercise program in MDD patients in real-life conditions?
The experimental group will receive an exercise intervention as an add-on to their usual treatment (antidepressant treatment prescribed by the attending specialist). Researchers will compare to a control group, which will only receive standard treatment (antidepressant treatment prescribed by the attending specialist) and will be instructed to not change their usual physical activity. The aim is to see if a physical exercise intervention would induce a significant improvement in depressive symptoms and which mechanisms are responsible for this result.
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.
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.
Parallel
Physical Exercise
Other interventionDaily walking. Participants will be given an activity band to self-monitor the number of steps they walk each day during the 12-week intervention period. Each participant must reach a certain number of daily steps with a progressive goal adjusted to the number of steps from the previous week. The goal is set considering the superior number to the median of steps of the preceding week. Weekly combined exercise sessions (aerobic + strength exercise) 2 sessions of 60 minutes per week in a 12-week program. The exercise intervention will combine the use of elastic bands and the body weight. First, 5 minutes of warm-up; second, training circuit with low-intensity strength exercises alternating work and rest times using rhythmic music. Upper, lower and middle body exercises will alternate. The program will progress in intensity, work: rest ratio, and technical difficulty of the exercises. At the end of the main part, there will be a cool-down and stretching for 5 minutes.
Antidepressant medication (ADM)
DrugPatients will receive their standard antidepressant treatment prescribed by their psychiatrist.
Inflammatory and oxidative stress biomarkers
Nrf2 activity will be measured in circulating monocytes and through transcriptomic analysis of redox and inflammation related genes. Plasma levels of hs C-reactive protein (CRP), interleukin 6 (hs-IL-6) and tumoral nechrosis factor alfa (hs- TNF-alfa) will be analyzed.
Brain imaging
It will be evaluated using Magnetic Resonance Imaging. Four different sequences will be acquired: a) a T2-FLAIR sequence; b) a 3D T1w MPRAGE sequence; c) a Diffusion Weighted sequence and d) a T2 resting-state sequence. These data will be used to discard any neurological issues, to evaluate structural changes, and for other images coregistration, to evaluate the integrity of white matter and structural connectivity, and to evaluate functional connectivity.
Clinical evaluation
The change in depression symptoms will be measured with the HAM-D17 scale. Duration of illness, number of episodes, current treatments, resistance antidepressant treatment index (Thase) will also be assessed.
Cognitive evaluation
Learning and verbal memory through the Hopkins Verbal Learning Test-Revised (HVLT-R); executive functioning through the Trail Making Test part B (TMT-B); processing speed through the Salthouse Perceptual Comparison Test (SPCT).
Functioning and Well-Being
The patient's functioning will be assessed through the WHO-DAS-II and well-being will be measured with the Cantrill ladder.
Muscle strength
It will be directly measured through a handheld dynamometer (TKK 5401 Grip-D, Takey, Tokyo, Japan) and a dynamometer for the upper and lower extremities (Lafayette Instruments dynamometer, Lafayette, Ind).
Cardiorespiratory fitness
It will be measured using the Incremental Shuttle Walk Test with blood gas analysis. The Incremental Shuttle Walk Test is performed on a flat 10-meter course marked by two cones. Participants are guided by auditory stimuli, which indicate when to increase speed (three beeps) and change direction at the end of the course (one beep). The test ends when the participant is more than 0.5 meters from the cone when the beep sounds (twice consecutively), reports being too short to continue, or experiences some discomfort that prevents them from continuing.
Click on the lead sponsor to view all of their trials.
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Lead sponsor
Hospital Universitario La Paz
Collaborator
Hospital Universitario Ramon y Cajal
Collaborator
Hospital Universitario Principe de Asturias
Collaborator
Quirón Madrid University Hospital
Collaborator
Universidad Autonoma de Madrid
Collaborator
Centro de Investigación Biomédica en Red de Salud Mental
Collaborator
Puerta de Hierro University Hospital
Collaborator
