protocolSection identificationModule nctId: NCT06377254, orgStudyIdInfo id: BB/X015173/1, briefTitle: Multi-organ Responses to CHronic Physical Activity and INactivity, acronym: CHAIN, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-03-12, primaryCompletionDateStruct date: 2027-12-17, completionDateStruct date: 2028-10-31, studyFirstPostDateStruct date: 2024-04-22, lastUpdatePostDateStruct date: 2024-04-22, sponsorCollaboratorsModule leadSponsor name: University of Nottingham, class: OTHER, collaborators name: Biotechnology and Biological Sciences Research Council, descriptionModule briefSummary: Life expectancy has been increasing for the last 150 years, but the maintenance of health has not kept pace with increased lifespan, and on average, UK adults spend the last decade of life in poor-health, with major consequences for society and the individual.Persistent physical inactivity is thought to be a key contributing factor to the risk of poor health and functional decline occurring in middle-aged and older adults. It is therefore concerning that most middle-aged adults spend \>8hrs/day being sedentary, with average step count of 3000-4000 steps/day.To be able to holistically assess the effectiveness of future strategies to address age-related decline in health, and devise public health messages to help individuals reach older age in better health, it is essential that the complex physiological effects that activity and inactivity have across biological systems are characterised.The goal of this intervention study is to compare the impact of physical activity and inactivity on body functioning. Twenty moderately active participants will decrease their physical activity for six months to match the average amount carried out by middle-aged people in the UK. They will then undertake 3-months of reconditioning training to restore their fitness. In addition, twenty sedentary participants will increase their physical activity to UK recommended levels for six months.Before and at points during the intervention period, participants will be asked to make some measurements at home and attend the University of Nottingham to have multiple assessments made. These include;* fitness, muscle strength and function tests,* completion of questionnaires and computer-based brain puzzles* having muscle and fat tissue biopsies and blood samples taken.* The study also involves having MRI scans.This 5-year study will commence in January 2024, with participant recruitment starting in March 2024 and finishing in May 2027., conditionsModule conditions: Sedentary Behavior, conditions: Metabolic Syndrome, conditions: Age-related Cognitive Decline, conditions: Age-Related Sarcopenia, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: NON_RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Non-randomised, parallel design lifestyle intervention, primaryPurpose: BASIC_SCIENCE, maskingInfo masking: SINGLE, maskingDescription: Those undertaking analysis of biological samples and MRI data will be masked as to the group the participant is allocated to., whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 40, type: ESTIMATED, armsInterventionsModule interventions name: Decreased Physical Activity, interventions name: Increased Physical activity, outcomesModule primaryOutcomes measure: Change in Cardiorespiratory fitness (VO2 max), secondaryOutcomes measure: Change in Isometric leg strength, secondaryOutcomes measure: Change in time to leg fatigue, secondaryOutcomes measure: Change in incremental area under the curve (iAUC) for blood glucose concentration, secondaryOutcomes measure: Change in iAUC for serum insulin concentration, secondaryOutcomes measure: Change in fasting glucose oxidation rate, secondaryOutcomes measure: Change in 'fed' glucose oxidation rate, secondaryOutcomes measure: Change in Short Form Health Survey (SF36) Questionnaire aggregated normalised 'physical' score, secondaryOutcomes measure: Change in Short Form Health Survey (SF36) Questionnaire aggregated and normalised 'mental' score, secondaryOutcomes measure: Change in World Health Organisation Quality of Life (WHOQoL) score, secondaryOutcomes measure: Change in Pittsburgh Sleep Quality Index (PSQI), secondaryOutcomes measure: Change in Stroop test; % Accuracy, secondaryOutcomes measure: Change in Stroop test; reaction time, secondaryOutcomes measure: Change in four-choice reaction time test; % Accuracy, secondaryOutcomes measure: Change in four-choice reaction time test; reaction time, secondaryOutcomes measure: Change in card sort test; % Accuracy, secondaryOutcomes measure: Change in card sort test; reaction time, secondaryOutcomes measure: Change in Logical reasoning test; % accuracy, secondaryOutcomes measure: Change in Logical reasoning test; reaction time, secondaryOutcomes measure: Change in serial subtractions test; number of responses in 2 minutes, secondaryOutcomes measure: Change in Corsi blocks test; score, secondaryOutcomes measure: Change in Muscle protein synthesis rate, secondaryOutcomes measure: Change in Muscle protein breakdown rate, secondaryOutcomes measure: Change in whole body fat volumes, secondaryOutcomes measure: Change in liver fat volumes, secondaryOutcomes measure: Change in thigh muscle fat volumes, secondaryOutcomes measure: Change in whole body muscle volumes, secondaryOutcomes measure: Change in muscle phosphocreatine synthesis rate, secondaryOutcomes measure: Change in cerebral volume, secondaryOutcomes measure: Change in cortical thickness, secondaryOutcomes measure: Change in plasma metabolome, otherOutcomes measure: Fasting blood lipid concentration, otherOutcomes measure: Fasting blood lipid concentration, otherOutcomes measure: Fasting blood lipid concentration, otherOutcomes measure: Fasting blood lipid concentration, otherOutcomes measure: Fasting blood lipid concentration, otherOutcomes measure: liver function test: alanine transaminase (ALT), otherOutcomes measure: liver function test: alanine transaminase (ALT), otherOutcomes measure: liver function test: alanine transaminase (ALT), otherOutcomes measure: liver function test: alanine transaminase (ALT), otherOutcomes measure: liver function test: alanine transaminase (ALT), otherOutcomes measure: liver function test: aspartate aminotransferase (AST), otherOutcomes measure: liver function test: aspartate aminotransferase (AST), otherOutcomes measure: liver function test: aspartate aminotransferase (AST), otherOutcomes measure: liver function test: aspartate aminotransferase (AST), otherOutcomes measure: liver function test: aspartate aminotransferase (AST), otherOutcomes measure: liver function test: Bilirubin, otherOutcomes measure: liver function test: Bilirubin, otherOutcomes measure: liver function test: Bilirubin, otherOutcomes measure: liver function test: Bilirubin, otherOutcomes measure: liver function test: Bilirubin, otherOutcomes measure: liver function test: Albumin, otherOutcomes measure: liver function test: Albumin, otherOutcomes measure: liver function test: Albumin, otherOutcomes measure: liver function test: Albumin, otherOutcomes measure: liver function test: Albumin, otherOutcomes measure: liver function test: Gamma glutamyl transferase (GGT), otherOutcomes measure: liver function test: Gamma glutamyl transferase (GGT), otherOutcomes measure: liver function test: Gamma glutamyl transferase (GGT), otherOutcomes measure: liver function test: Gamma glutamyl transferase (GGT), otherOutcomes measure: liver function test: Gamma glutamyl transferase (GGT), otherOutcomes measure: Blood Haemoglobin concentration, otherOutcomes measure: Blood Haemoglobin concentration, otherOutcomes measure: Blood Haemoglobin concentration, otherOutcomes measure: Blood Haemoglobin concentration, otherOutcomes measure: Blood Haemoglobin concentration, eligibilityModule sex: ALL, minimumAge: 55 Years, maximumAge: 65 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: David Greenfield Human Physiology Unit, status: RECRUITING, city: Nottingham, state: Notts, zip: NG72UH, country: United Kingdom, contacts name: Sara Brown, role: CONTACT, phone: +44(0)115 8230434, email: sara.brown@nottingham.ac.uk, contacts name: Joanne Mallinson, PhD, role: CONTACT, phone: +44(0)1158230434, email: joanne.mallinson@nottingham.ac.uk, contacts name: Paul Greenhaff, PhD, role: PRINCIPAL_INVESTIGATOR, contacts name: Liz Simpson, PhD, role: SUB_INVESTIGATOR, contacts name: Joanne Mallinson, PhD, role: SUB_INVESTIGATOR, contacts name: Abhishek Sheth, MD, role: SUB_INVESTIGATOR, contacts name: Penny Gowland, PhD, role: SUB_INVESTIGATOR, contacts name: Sue Francis, PhD, role: SUB_INVESTIGATOR, contacts name: Rosemary Nicholls, PhD, role: SUB_INVESTIGATOR, contacts name: Aline Nixon, role: SUB_INVESTIGATOR, contacts name: Sara Brown, role: SUB_INVESTIGATOR, contacts name: Donald Peden, PhD, role: SUB_INVESTIGATOR, geoPoint lat: 52.9536, lon: -1.15047, hasResults: False