Major Depressive Disorder Clinical Trial
— CARE-MINDOfficial title:
Inflammatory and Brain Mechanisms and Clinical and Cognitive Effects of an Exercise Intervention in Major Depressive Disorder: a Randomised Longitudinal Clinical Trial.
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.
Status | Not yet recruiting |
Enrollment | 124 |
Est. completion date | December 31, 2026 |
Est. primary completion date | September 1, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | 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; Ongoing alcohol use and drug use will be assessed through the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Abuse Screening Test (DAST-10) respectively since it may affect inflammation. - Excessive physical exercise assessed through certain questions extracted from the European Prospective Investigation into Cancer and Nutrition Physical Activity questionnaire. |
Country | Name | City | State |
---|---|---|---|
Spain | Hospital Universitario de La Princesa | Madrid | |
Spain | Hospital Universitario La Paz | Madrid | |
Spain | Hospital Universitario Príncipe de Asturias | Madrid | |
Spain | Hospital Universitario Ramón y Cajal | Madrid |
Lead Sponsor | Collaborator |
---|---|
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa | Centro de Investigación Biomédica en Red de Salud Mental, Hospital Universitario La Paz, Hospital Universitario Principe de Asturias, Hospital Universitario Ramon y Cajal, Quirón Madrid University Hospital, Universidad Autonoma de Madrid |
Spain,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Primary | 24-hours activity behaviors | Physical activity, sedentarism and sleep will be objectively measured using a multi-sensor monitor (ActiGraph GT9X Link, Pensacola, FL, USA) over a 24-hour 7 days period at the onset of the exercise intervention and 7 days post-intervention. Only participants who carry the monitor for at least 95% of the day (1368 minutes) will be included in the analysis. This monitor is worn as a watch and will be placed on the non-dominant wrist. Daily steps will be recorded through the activity band (MiBand6). | 1. Onset of the intervention; 2. 7 Days after intervention | |
Primary | Physical activity information | It will be assessed through the European Prospective Investigation into Cancer and Nutrition physical activity questionnaire (EPIC). | 1. Before Randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization | |
Secondary | 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) and the short form of the Wisconsin Card Sorting Test (WCST-64); processing speed through the Salthouse Perceptual Comparison Test (SPCT). | 1. Before Randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization | |
Secondary | 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. | 1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization | |
Secondary | 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). | 1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization | |
Secondary | Cardiorespiratory fitness | It will be measured with an established test protocol on a bicycle ergometer. During a ramp protocol workload increases of 1 W every 6 s will be applied starting from an initial load of 0 W, with a pedal cadence of 60 -70 rpm throughout the test. | 1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization | |
Secondary | Anthropometric evaluation | Weight will be assessed through a stadiometer (SECA) and waist circumference with a metric tape (Harpenden anthropometric tape, Holtain Ltd). Body Mass Index, waist-to-hip ratio and blood pressure also will be assessed. | 1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization | |
Secondary | Metabolic biomarkers | Serum levels of glucose, glycosylated haemoglobin and lipid profile. | 1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization | |
Secondary | Nutrition habits | It will be assessed with the Food Frequency Questionnaire (FFQ). | 1. Before randomization; 2. 12 Weeks after the beggining of intervention; 3. 1 Year after randomization |
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