protocolSection identificationModule nctId: NCT06387732, orgStudyIdInfo id: 161223, briefTitle: Mechanisms Underlying Antidepressant Effects of Physical Activity, acronym: LIFE, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-06, primaryCompletionDateStruct date: 2027-08, completionDateStruct date: 2028-01, studyFirstPostDateStruct date: 2024-04-29, lastUpdatePostDateStruct date: 2024-04-29, sponsorCollaboratorsModule leadSponsor name: University College, London, class: OTHER, collaborators name: King's College London, collaborators name: Queen Mary University of London, collaborators name: University of Dublin, Trinity College, descriptionModule briefSummary: It is well established that any level of physical activity can help prevent and treat depression, with more strenuous activity having a greater effect. Understanding the mechanisms driving this antidepressant effect is important because it could allow exercise programmes to be made more effective, accessible, and targeted. Such knowledge could contribute to social prescribing, increasingly a priority for mental healthcare. Importantly, physical activity is highly scalable, low cost, well suited to early intervention, and has beneficial impacts on physical health co-morbidities. This trial may provide initial indications of whether there are sub-groups of depressed individuals who are particularly likely to benefit from physical activity, lead to strategies to personalise physical activity prescription based on motivational factors, and pave the way for augmentative approaches, for example combining physical activity with psychological interventions.To date the mechanisms driving the antidepressant effects of physical activity in humans are poorly understood. Building on links between depressive symptoms, reward processing and dopamine, plus evidence from animal studies that physical activity is anti-inflammatory and boosts both dopamine and reward processing, the overarching aim of this trial is to understand the mechanisms underlying the effects of physical activity in depression, focusing on the concept of motivation.The key objective is to conduct a randomised controlled trial (RCT) in N=250 depressed participants comparing aerobic exercise to a stretching/relaxation control condition, examining a range of mechanistic factors. The proposed trial will examine the impact of physical activity at multiple, linked potential levels of explanation: (1) immune-metabolic markers; (2) dopamine synthesis capacity; (3) activation in the brain's reward and effort processing circuitry;(4) effort-based decision making incorporating computational analysis; and (5) symptom networks based on fine-grained, daily measurements., conditionsModule conditions: Depression, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: The trial will use a single-site parallel group design with depressed participants randomised to eight weeks of either 45 minutes of aerobic exercise of moderate-to-vigorous activity (experimental group: three times per week, N=125) or 45 minutes of non-aerobic stretching/guided relaxation (control group: three times per week, N=125)., primaryPurpose: TREATMENT, maskingInfo masking: SINGLE, maskingDescription: The control arm is stretching and relaxation. Prior research indicates that participants have similar efficacy expectations regarding mild stretching and aerobic exercise, which will help to improve masking. Due to the nature of the interventions, it is not possible for the participants to be masked as to the intervention they are undergoing, but all study information will be agnostic about which intervention we expect to be more effective, and all analysis will be performed by blinded staff. The trial will assess expectations and preferences about the intervention conditions, allowing for sensitivity analyses., whoMasked: PARTICIPANT, enrollmentInfo count: 250, type: ESTIMATED, armsInterventionsModule interventions name: Aerobic exercise, interventions name: Stretching and relaxation, outcomesModule primaryOutcomes measure: Patient Health Questionnaire-9 score, secondaryOutcomes measure: Physical activity, secondaryOutcomes measure: Aerobic capacity: CPET, secondaryOutcomes measure: Ecological Momentary Assessment, secondaryOutcomes measure: Inflammatory response (cytokines), secondaryOutcomes measure: Inflammatory response (genetic markers), secondaryOutcomes measure: Inflammatory response (flow cytometry immunophenotype), secondaryOutcomes measure: Neuroendocrine system, secondaryOutcomes measure: Metabolic function, secondaryOutcomes measure: Dopamine synthesis capacity, secondaryOutcomes measure: Functional magnetic resonance imaging (fMRI) during cognitive tasks, secondaryOutcomes measure: Online cognitive tasks, secondaryOutcomes measure: Depression symptoms, secondaryOutcomes measure: Anxiety (GAD7 score), secondaryOutcomes measure: Anxiety (STAI score), secondaryOutcomes measure: Anhedonia (SHAPS score), secondaryOutcomes measure: Anhedonia (DARS score), secondaryOutcomes measure: Apathy, secondaryOutcomes measure: Fatigue, secondaryOutcomes measure: Cognitive impairment, secondaryOutcomes measure: Self-efficacy, secondaryOutcomes measure: Self-esteem, secondaryOutcomes measure: Sleep quality, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 60 Years, stdAges: ADULT, contactsLocationsModule, hasResults: False