Cerebral and Anti-inflammatory Response Through Exercise - Mechanisms In Depressive Disorders

NCT06450704 | Recruiting

• 1 other identifier: 5561
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Major Depressive Disorder; Inflammatory Response

Keywords

Major Depressive Disorder; Physical Exercise; Inflammation; Neuroimaging

Outcome Measures

Primary Outcomes (3)

• 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.

  1. Before randomization; 2. 12-weeks after the beggining of intervention; 3. 1 year after randomization

• 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.

  1. Before randomization; 2. 12 Weeks after the beggining of intervention

• 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.

  1. Before Randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization

Secondary Outcomes (8)

• Cognitive evaluation

  1. Before Randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization

• Functioning and Well-Being

  1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization

• Muscle strength

  1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization

• Cardiorespiratory fitness

  1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization

• 24-hours physical activity behaviors

  1. Before Randomization; 2. 12 Weeks after the beggining of intervention

Study Arms (2)

Exercise intervention group (EG)

EXPERIMENTAL

Major Depressive Disorder patients will receive the exercise intervention for 12 weeks as an add-on to their usual treatment (antidepressant treatment prescribed by the attending specialist). They will gradually increase their levels of physical activity by daily walking and will conduct aerobic and muscle strength activities 2 days per week. The program will be supervised by a physical education and sports professional.

Other: Physical Exercise; Drug: Antidepressant medication (ADM)

Control group (CG)

ACTIVE COMPARATOR

Major Depressive Disorder patients will only receive standard treatment (antidepressant treatment prescribed by the attending specialist) and will be instructed to not change their usual physical activity.

Drug: Antidepressant medication (ADM)

Interventions

Physical Exercise OTHER

Daily 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.

Also known as: Therapeutic Exercise, physical activity, Exercise

Exercise intervention group (EG)

Antidepressant medication (ADM) DRUG

Patients will receive their standard antidepressant treatment prescribed by their psychiatrist.

Control group (CG); Exercise intervention group (EG)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa: lead
• 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
• Hospital Universitario Puerta de Hierro de Majadahonda: collaborator

Study Sites (5)

Hospital Universitario Príncipe de Asturias

Alcalá de Henares, Madrid, 28805, Spain

RECRUITING

Hospital Universitario de La Princesa

Madrid, Madrid, 28006, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, 28222, Spain

RECRUITING

Related Publications (12)

• Ravindran AV, Balneaves LG, Faulkner G, Ortiz A, McIntosh D, Morehouse RL, Ravindran L, Yatham LN, Kennedy SH, Lam RW, MacQueen GM, Milev RV, Parikh SV; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments. Can J Psychiatry. 2016 Sep;61(9):576-87. doi: 10.1177/0706743716660290. Epub 2016 Aug 2.

  PMID: 27486153 BACKGROUND

• Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.

  PMID: 17074942 BACKGROUND

• Mathur N, Pedersen BK. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm. 2008;2008:109502. doi: 10.1155/2008/109502. Epub 2009 Jan 11.

  PMID: 19148295 BACKGROUND

• Dishman RK, Berthoud HR, Booth FW, Cotman CW, Edgerton VR, Fleshner MR, Gandevia SC, Gomez-Pinilla F, Greenwood BN, Hillman CH, Kramer AF, Levin BE, Moran TH, Russo-Neustadt AA, Salamone JD, Van Hoomissen JD, Wade CE, York DA, Zigmond MJ. Neurobiology of exercise. Obesity (Silver Spring). 2006 Mar;14(3):345-56. doi: 10.1038/oby.2006.46.

  PMID: 16648603 BACKGROUND

• Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009 Feb;71(2):171-86. doi: 10.1097/PSY.0b013e3181907c1b. Epub 2009 Feb 2.

  PMID: 19188531 BACKGROUND

• Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.

  PMID: 20015486 BACKGROUND

• Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016 Jan;16(1):22-34. doi: 10.1038/nri.2015.5.

  PMID: 26711676 BACKGROUND

• Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull. 2014 May;140(3):774-815. doi: 10.1037/a0035302. Epub 2014 Jan 13.

  PMID: 24417575 BACKGROUND

• Zuo C, Cao H, Song Y, Gu Z, Huang Y, Yang Y, Miao J, Zhu L, Chen J, Jiang Y, Wang F. Nrf2: An all-rounder in depression. Redox Biol. 2022 Dec;58:102522. doi: 10.1016/j.redox.2022.102522. Epub 2022 Oct 31.

  PMID: 36335763 BACKGROUND

• Done AJ, Traustadottir T. Nrf2 mediates redox adaptations to exercise. Redox Biol. 2016 Dec;10:191-199. doi: 10.1016/j.redox.2016.10.003. Epub 2016 Oct 14.

  PMID: 27770706 BACKGROUND

• Krogh J, Saltin B, Gluud C, Nordentoft M. The DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of strength versus aerobic versus relaxation training for patients with mild to moderate depression. J Clin Psychiatry. 2009 Jun;70(6):790-800. doi: 10.4088/jcp.08m04241.

  PMID: 19573478 BACKGROUND

• Stubbs B, Vancampfort D, Rosenbaum S, Ward PB, Richards J, Soundy A, Veronese N, Solmi M, Schuch FB. Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression. J Affect Disord. 2016 Jan 15;190:457-466. doi: 10.1016/j.jad.2015.10.019. Epub 2015 Oct 29.

  PMID: 26551405 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Motor Activity; Inflammation

Interventions

Exercise; Exercise Therapy; Antidepressive Agents

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Pilar López García, PhD

  Universidad Autonoma de Madrid

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Javier Gómez Cumplido, PT, MSc

CONTACT

(+34) 633467602; javier.gomezc@uam.es

Pilar López García, PhD

CONTACT

(+34) 91 497 54 48; p.lopez@uam.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 10, 2024
• Study Start: April 21, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)