[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100656578":3},{"organization":4,"outcomesModule":7,"designInfo":69,"detailedDescription":77,"studyPopulation":68,"armGroups":78,"interventions":93,"overallOfficials":68,"centralContacts":98,"locations":104,"responsibleParty":120,"collaborators":122,"id":128,"slug":129,"hasResults":130,"nctId":131,"briefTitle":132,"officialTitle":132,"acronym":133,"eligibilityCriteria":134,"healthyVolunteers":135,"sex":136,"minAge":137,"maxAge":138,"enrollmentInfo":139,"targetDuration":68,"studyType":142,"phases":143,"briefSummary":145,"conditions":146,"keywords":151,"overallStatus":107,"whyStopped":68,"lastUpdateSubmitDate":157,"lastUpdatePostDateStruct":158,"startDateStruct":161,"completionDateStruct":163,"leadSponsor":165,"locationsCount":166},{"fullName":5,"class":6},"Fundación para la Investigación del Hospital Clínico de Valencia","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":16,"otherOutcomes":68},[9,13],{"measure":10,"description":11,"timeFrame":12},"Change in Mitochondrial Oxidative Phosphorylation (OXPHOS) Capacity in Skeletal Muscle","Mitochondrial oxidative phosphorylation capacity will be assessed in permeabilised skeletal muscle fibre bundles obtained from vastus lateralis biopsies using high-resolution respirometry (Oxygraph-2k, Oroboros Instruments). OXPHOS capacity will be expressed as oxygen flux normalised to muscle tissue wet weight (pmol O₂·s-¹·mg-¹ wet tissue).","Baseline and after 6 weeks of supervised resistance training",{"measure":14,"description":15,"timeFrame":12},"Change in Mitochondrial Oxidative Phosphorylation (OXPHOS) Capacity in Peripheral Blood Mononuclear Cells (PBMCs)","Mitochondrial oxidative phosphorylation capacity will be assessed in permeabilised peripheral blood mononuclear cells (PBMCs) using high-resolution respirometry (Oxygraph-2k, Oroboros Instruments). OXPHOS capacity will be expressed as oxygen flux normalised to cell number (pmol O₂·s-¹·10⁶ cells-¹).",[17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65],{"measure":18,"description":19,"timeFrame":12},"Change in Mitochondrial Quality Control Protein Expression in Skeletal Muscle","Protein expression of selected markers involved in mitochondrial dynamics, mitophagy, and biogenesis, including MFN1, MFN2, DRP1, PINK1, PARKIN, PGC-1α, and TFAM, will be assessed in vastus lateralis muscle biopsies by Western blot. Protein abundance will be quantified by densitometry, normalised to an appropriate loading control, and expressed as fold change relative to baseline.",{"measure":21,"description":22,"timeFrame":12},"Change in Whole-Body Lean Mass","Whole-body lean mass will be assessed by dual-energy X-ray absorptiometry (DXA) and expressed in kilograms (kg).",{"measure":24,"description":25,"timeFrame":12},"Change in Whole-Body Fat Mass","Whole-body fat mass will be assessed by dual-energy X-ray absorptiometry (DXA) and expressed in kilograms (kg).",{"measure":27,"description":28,"timeFrame":12},"Change in 6-Minute Walk Test Distance","Functional exercise capacity will be assessed using the 6-Minute Walk Test (6MWT). The total distance walked during 6 minutes will be recorded in metres (m), with a greater distance indicating better functional exercise capacity.",{"measure":30,"description":31,"timeFrame":12},"Change in Blood Glucose-6-Phosphate Dehydrogenase (G6PD) Activity","Glucose-6-phosphate dehydrogenase (G6PD) activity will be measured in blood as a systemic redox-related biomarker and expressed as units per gram of haemoglobin (U\u002Fg Hb).",{"measure":33,"description":34,"timeFrame":12},"Change in Skeletal Muscle Cell-Type-Specific Transcriptomic Profiles","Single-nucleus RNA sequencing will be performed on vastus lateralis muscle biopsies to characterise cell-type-specific gene expression profiles in skeletal muscle. Transcript abundance will be quantified as normalised gene expression counts within identified cell populations.",{"measure":36,"description":37,"timeFrame":12},"Change in Gut Microbiota Alpha Diversity","Gut microbiota alpha diversity will be assessed using the Shannon diversity index. The Shannon index is unitless, with higher values indicating greater microbial diversity.",{"measure":39,"description":40,"timeFrame":12},"Change in Quadriceps Muscle Thickness","Quadriceps muscle thickness will be assessed by ultrasound and expressed in millimetres (mm).",{"measure":42,"description":43,"timeFrame":12},"Change in Skeletal Muscle Fibre Cross-Sectional Area","Skeletal muscle fibre cross-sectional area will be assessed by histological analysis of vastus lateralis muscle biopsies and expressed in square micrometres (µm²).",{"measure":45,"description":46,"timeFrame":12},"Change in Short Physical Performance Battery (SPPB) Score","Lower-extremity physical function will be assessed using the Short Physical Performance Battery (SPPB), which includes standing balance, usual gait speed, and repeated chair stands. The total score ranges from 0 to 12 points, with higher scores indicating better physical performance.",{"measure":48,"description":49,"timeFrame":12},"Change in FallSkip Test Performance Time","Functional mobility and fall-related performance will be assessed using the FallSkip test. Time to complete the test will be recorded in seconds (s), with a shorter time indicating better performance.",{"measure":51,"description":52,"timeFrame":12},"Change in Blood Malondialdehyde (MDA) Levels","Malondialdehyde (MDA) levels will be measured in blood as a marker of systemic lipid peroxidation and expressed in micromoles per litre (µmol\u002FL).",{"measure":54,"description":55,"timeFrame":12},"Change in Fried Frailty Phenotype Score","Frailty status will be assessed using the Fried Frailty Phenotype, based on five criteria: unintentional weight loss, self-reported exhaustion, low physical activity, slow walking speed, and weakness. The total score ranges from 0 to 5, with higher scores indicating greater frailty.",{"measure":57,"description":58,"timeFrame":12},"Change in Frailty Classification Assessed by the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI)","Frailty will be assessed using the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI), which combines fatigue, loss of appetite, grip strength, functional difficulties, and physical activity. Participants will be classified as non-frail, pre-frail, or frail according to the SHARE-FI algorithm, with higher frailty categories indicating greater frailty.",{"measure":60,"description":61,"timeFrame":12},"Change in Quadriceps Extension 3-Repetition Maximum (3RM)","Quadriceps muscle strength will be assessed using the 3-repetition maximum (3RM) during the quadriceps extension exercise. The maximum load successfully completed for three repetitions will be recorded in kilograms (kg), with higher values indicating greater muscle strength.",{"measure":63,"description":64,"timeFrame":12},"Change in Skeletal Muscle Chromatin Accessibility Profiles Assessed by ATAC-seq","Chromatin accessibility will be assessed in skeletal muscle samples using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). Genome-wide chromatin accessibility profiles will be quantified using normalised accessibility signals across identified regulatory regions.",{"measure":66,"description":67,"timeFrame":12},"Change in Plasma Proteomic Profiles","Plasma proteomic profiling will be performed using liquid chromatography-tandem mass spectrometry (LC-MS\u002FMS) to characterise changes in circulating protein abundance. Protein abundance will be quantified and expressed as normalised relative abundance values.",null,{"allocation":70,"interventionModel":71,"interventionModelDescription":68,"primaryPurpose":72,"observationalModel":68,"timePerspective":68,"maskingInfo":73},"NON_RANDOMIZED","PARALLEL","TREATMENT",{"masking":74,"maskingDescription":68,"whoMasked":75},"SINGLE",[76],"INVESTIGATOR","Background and Rationale:\n\nFrailty is a multifactorial geriatric syndrome characterized by a decline in physiological reserves across multiple systems, leading to reduced resilience, weakness, and increased vulnerability to stressors such as acute illness, injury, or surgery. Clinically, frailty manifests as diminished strength, slowed mobility, exhaustion, and unintentional weight loss, often culminating in disability, hospitalization, and premature mortality. Among its core biological features, skeletal muscle deterioration, encompassing losses in muscle mass, contractile function, and regenerative capacity, plays a central role in the onset and progression of functional impairment and dependence in older adults.\n\nAt the cellular level, mitochondrial dysfunction has emerged as a key pathophysiological driver of frailty and sarcopenia. Mitochondria are essential for energy production, redox balance, and regulation of calcium homeostasis, apoptosis and inflammation. With aging, mitochondrial content, dynamics, and efficiency decline, leading to reduced ATP generation, increased reactive oxygen species (ROS) production, and accumulation of damaged mitochondrial DNA (mtDNA). These alterations compromise muscle bioenergetics and promote catabolic pathways that accelerate muscle atrophy. Moreover, defective mitophagy, an essential quality control process, leads to the persistence of dysfunctional organelles, perpetuating oxidative stress and inflammation.\n\nSystemic metabolic disturbances further exacerbate these mitochondrial deficits. A chronic condition such as type 2 diabetes mellitus (T2DM) is frequently associated with frailty and share common mechanisms. Increased levels of pro-inflammatory cytokines (e.g., IL-6, TNF-α) and mitochondrial stress markers signal ongoing tissue damage and maladaptive stress responses. These interactions between metabolic dysregulation, inflammation, and mitochondrial dysfunction form a self-reinforcing cycle that underlies the molecular pathogenesis of frailty.\n\nExercise training, and particularly resistance exercise, is among the most potent non-pharmacological interventions to counteract frailty-related declines. Regular exercise improves muscle mass and strength, enhances glucose and lipid metabolism, and promotes mitochondrial biogenesis and function through activation of key molecular pathways. Furthermore, exercise induces the release of myokines that mediate intercellular communication between muscle and distant organs, influencing systemic metabolism, inflammation, and repair processes. However, despite well-established clinical benefits, the molecular and cellular mechanisms by which exercise remodels mitochondrial networks and restores metabolic homeostasis in frail or metabolically compromised individuals remain incompletely understood.\n\nElucidating how exercise modulates mitochondrial quality control, energy metabolism, and signaling pathways in the context of frailty could reveal new therapeutic targets to delay or reverse physiological decline. Integrating metabolic markers with molecular indicators of mitochondrial stress and muscle-derived factors offers a multidimensional approach to understanding the bioenergetic and inflammatory signatures of frailty and their reversibility through targeted interventions.\n\nStudy Objectives:\n\nThis project aims to:\n\n1. Determine the contribution of skeletal muscle mitochondrial dysfunction to frailty in older adults, including those with T2DM.\n2. Evaluate the effects of a 6-week supervised resistance training program on functional, molecular, and metabolic outcomes.\n3. Characterize adaptations within the perimuscular interstitial microenvironment (fibroblasts, immune cells, vascular, neural and muscle stem cells as well as extracellular matrix components) that may mediate exercise-induced improvements in muscle health.\n\nThrough these objectives, the study seeks to integrate clinical, physiological, and molecular analyses to uncover mechanisms linking mitochondrial remodelling, aging, and exercise adaptation\n\nStudy Design:\n\nThis is a longitudinal, interventional study including 120 participants divided into three groups:\n\n* Older adults with T2DM (≥65 years) - 40 participants\n* Healthy older adults (≥65 years) - 40 participants\n* Young healthy adults (19-35 years) - 40 participants (controls) All participants will complete baseline assessments, a 6-week supervised resistance training program, and post-intervention evaluations. Optional muscle biopsies will be obtained from participants who consent before and after training.\n\nIntervention:\n\nParticipants will undergo a 6-week progressive resistance training program targeting the quadriceps muscles, consisting of two sessions per week (a total of 12 sessions), each lasting 30-50 minutes.\n\n* Exercises include leg press and knee extension, progressing from submaximal to near-maximal effort as tolerated.\n* Training intensity and progression will be individualised according to functional capacity.\n* All sessions will be supervised by qualified exercise specialists to ensure safety and adherence.\n\nThis short, structured, and closely monitored training protocol was designed to be both safe and feasible for older adults with varying levels of frailty or diabetes.\n\nAssessments and Procedures:\n\nBaseline and Post-Intervention Evaluations:\n\nParticipants will undergo comprehensive testing before and after the exercise program, including:\n\n* Blood sampling for metabolic, inflammatory, and aging biomarkers.\n* Body composition analysis using DXA, ultrasound, and bioimpedance.\n* Functional assessments of strength, balance, gait speed, and mobility.\n* Stool sampling for gut microbiota composition.\n* Optional muscle biopsies (quadriceps) under local anesthesia for mitochondrial and tissue-level analyses.\n\nMuscle Biopsy Analyses\n\nMuscle tissue samples will be used to examine:\n\n* Mitochondrial function, oxidative stress, and biogenesis markers.\n* Cellular and molecular characteristics of the perimuscular niche via single-nuclei and histological analyses.\n* Changes in fibrosis, immune infiltration, vascular density, and extracellular matrix remodelling following exercise.\n\nAll biopsy procedures will be performed by trained clinicians following hospital safety protocols, with local anaesthesia and post-procedure monitoring.\n\nOutcomes and Data Integration:\n\nThe study will generate a comprehensive dataset encompassing:\n\n* Clinical and functional outcomes: muscle strength, mobility, balance, and composite frailty scores.\n* Molecular and biochemical measures: mitochondrial respiration, oxidative stress and inflammatory markers, and pathways related to muscle regeneration.\n* Circulating biomarkers: metabolic, inflammatory, and aging-related factors.\n* Microbiome analyses: gut bacterial diversity and composition.\n* Cross-sectional comparisons: differences across age and diabetes status.\n* Longitudinal effects: pre- vs. post-intervention changes in functional and molecular endpoints.\n\nThis integrated approach will allow exploration of mechanistic links between exercise-induced mitochondrial remodelling, systemic inflammation, and functional improvements.\n\nSafety Considerations:\n\nThe exercise program carries minimal risk and will be supervised at all times. Potential risks include mild muscle soreness or fatigue. Blood sampling may cause minor bruising or lightheadedness. Muscle biopsy, when performed, carries a small risk of pain, bleeding, or infection; all procedures will be conducted by trained clinical personnel with appropriate monitoring and follow-up.\n\nParticipants' safety will be prioritised throughout the study, with adherence logs, post-biopsy monitoring, and regular communication with healthcare providers.\n\nPotential Benefits:\n\nParticipants may experience improvements in strength, balance, and mobility, as well as greater awareness of their health and functional capacity.\n\nBeyond individual benefits, this project is expected to provide key insights into:\n\n* The role of mitochondrial dysfunction and diabetes in age-related muscle decline.\n* The cellular mechanisms underlying exercise-induced rejuvenation of skeletal muscle.\n* Evidence-based strategies for designing personalised exercise programs to delay or prevent frailty.\n\nSignificance and Expected Impact:\n\nBy comparing diabetic and non-diabetic older adults with younger controls, this study will clarify the contribution of mitochondrial dysfunction and systemic metabolic stress to muscle aging and functional decline. It will also identify how short-term, supervised resistance training promotes beneficial adaptations within muscle fibers and their surrounding microenvironment.\n\nThe results will contribute to developing practical, safe, and effective interventions to maintain independence, improve quality of life, and reduce healthcare burden in aging populations. Ultimately, this project aims to bridge the gap between basic mitochondrial biology and translational geroscience, providing new insights into the prevention and management of frailty in older adults.",[79,85,89],{"label":80,"type":81,"description":82,"interventionNames":83},"Group of healthy trained old people","ACTIVE_COMPARATOR","Elderly patient without diagnosis of type 2 diabetes mellitus",[84],"Other: Short-duration resistance training",{"label":86,"type":81,"description":87,"interventionNames":88},"Group of type 2 diabetic trained old patients","Elderly patient diagnosed with type 2 diabetes mellitus",[84],{"label":90,"type":81,"description":91,"interventionNames":92},"Group of healthy trained young people","Young healthy control subjects",[84],[94],{"type":6,"name":95,"description":96,"armGroupLabels":97,"otherNames":68},"Short-duration resistance training","The exercise program will be personalized (based on functional status). This program will consist of 12 sessions spread over 6 weeks, two days a week, and will increase in duration (30-50 minutes). The lower body muscle group, targeting the quadriceps, will be trained with two exercises: leg press and quadriceps extension. The training intensity will be submaximal, progressing toward maximum. All patient groups, both controls and cases, will receive the same type of training.",[80,90,86],[99],{"name":100,"role":101,"phone":102,"phoneExt":68,"email":103},"Maria Carmen Gómez Cabrera, Doctor in Physiology","CONTACT","+34-666871805","carmen.gomez@uv.es",[105],{"facility":106,"status":107,"city":108,"state":68,"zip":109,"country":110,"countryCode":111,"cosmosGeoPoint":112,"geoPoint":117,"contacts":118},"University of Valencia\u002FHospital Clínico Universitario de València,","RECRUITING","Valencia","46010","Spain","ES",{"type":113,"coordinates":114},"Point",[115,116],-0.37966,39.47391,{"lat":116,"lon":115},[119],{"name":100,"role":101,"phone":102,"phoneExt":68,"email":103},{"type":121,"investigatorFullName":68,"investigatorTitle":68,"investigatorAffiliation":68,"oldNameTitle":68,"oldOrganization":68},"SPONSOR",[123,125],{"name":124,"class":6},"University of Valencia",{"name":126,"class":127},"Ministerio de Ciencia e Innovación, Spain","OTHER_GOV","100656578","involvement-of-muscle-mitochondrial-dysfunction-in-frailty-in-older-adults-role-of-exercise-100656578",false,"NCT07828847","Involvement of Muscle Mitochondrial Dysfunction in Frailty in Older Adults. Role of Exercise","MITOSTRENGTH","Inclusion Criteria:\n\n* Inclusion criteria for young controls\n\n  * Healthy young adults (18-35 years old)\n  * Without any pathology or treatment\n* Inclusion criteria for older controls\n\n  * Healthy older adults (65 years or older)\n  * Not currently enrolled in a resistance training program\n* Inclusion criteria for cases\n\n  * Age over 65 years\n  * Diagnosis of frailty or robustness\n  * Diagnosis of type 2 diabetes mellitus\n  * Glycosylated hemoglobin (HbA1c) less than 9%\n  * Treatment with metformin\n  * Not currently enrolled in a resistance training program\n\nExclusion Criteria:\n\n* Exclusion criteria for young controls\n\n  * Pregnancy or suspected pregnancy\n  * Body mass index greater than 35 kg\u002Fm2\n  * Treatment within the last 30 days with oral corticosteroids\n  * Edema or severe fluid regulation disorders that could alter bioimpedance results\n  * Allergy to the local anesthetic mepivacaine\n  * Prostheses, metal implants, or surgical staples lodinated or barium contrast for other imaging tests within the last 7 days\n* Exclusion criteria for older controls\n\n  * Decompensated and uncontrolled chronic diagnoses\n  * Body mass index greater than 35 kg\u002Fm2\n  * Treatment within the last 30 days with oral corticosteroids\n  * Systemic diseases, active oncological disease, liver cirrhosis, untreated hypothyroidism, or severe chronic obstructive pulmonary disease (COPD).\n  * Severe edema or fluid regulation disorders that could alter bioimpedance results\n  * Allergy to the local anesthetic mepivacaine\n  * Prostheses, metal implants, or surgical staples Iodinated or barium contrast for other imaging tests in the last 7 days\n* Exclusion criteria for cases\n\n  * Diagnosis of pre-frailty\n  * Age over 80 years\n  * Body mass index greater than 35 kg\u002Fm2\n  * Time since onset of diabetes mellitus type 2 less than 10 years\n  * Treatment with insulin\n  * Treatment with allopurinol\n  * Treatment with anticoagulant or antiplatelet drugs\n  * Treatment within the last 30 days with oral corticosteroids\n  * Advanced chronic complications of diabetes mellitus type 2 :\n\nRenal failure (clearance \\\u003C30 ml\u002Fmin\u002Fm2) Macroalbuminuria greater than 200 mg\u002Fg Ischemic vascular diseases (acute myocardial infarction) Myocardial infarction, angina, stroke) Proliferative retinopathy or laser therapy Ulcerated diabetic foot or lower limb amputations, except for digital amputations\n\n* Systemic diseases, active oncological disease, liver cirrhosis, untreated hypothyroidism, or severe chronic obstructive pulmonary disease\n* Physical limitations in the lower limbs (acute or acute-on-chronic inflammatory processes, limited joint range of motion, chronic pain (visual analogue scale for pain \\> or = 4, etc.)\n* Senile dementia\n* Edema or severe fluid regulation disorders that may alter bioimpedance results\n* Allergy to the local anesthetic mepivacaine\n* Pacemaker, metallic prostheses or implants, surgical staples, and radiopaque tubes or catheters Iodinated or barium contrast for other imaging tests within the last 7 days",true,"ALL","18 Years","83 Years",{"count":140,"type":141},120,"ESTIMATED","INTERVENTIONAL",[144],"NA","This study aims to investigate the role of skeletal muscle mitochondrial dysfunction in the development of frailty in older adults and to evaluate whether a short-term, supervised resistance training intervention can improve skeletal muscle health and physical function.\n\nFrailty is a common age-related condition associated with increased vulnerability to disability, hospitalisation, and loss of independence. It is characterised by features that may include weakness, fatigue, reduced physical activity, and slower walking speed. Mitochondrial dysfunction in skeletal muscle may contribute to the development of frailty and may be further influenced by chronic conditions such as type 2 diabetes mellitus (T2DM), which are associated with metabolic alterations, inflammation, oxidative stress, and insulin resistance.\n\nResistance training is an effective strategy to counteract age-related declines in muscle strength and physical function. However, the cellular and molecular mechanisms linking resistance training to improvements in mitochondrial function, skeletal muscle health, and resilience in older adults remain incompletely understood.\n\nThe study will include approximately 120 participants comprising older adults with T2DM, healthy older adults, and young healthy controls.\n\nAll participants will complete a 6-week supervised resistance training intervention, consisting of two sessions per week.\n\nAssessments performed before and after the intervention will include body composition, muscle morphology, physical performance, muscle strength, frailty, and blood-based biomarkers. Peripheral blood mononuclear cells (PBMCs) will be used to assess mitochondrial function, and plasma samples will be used for proteomic profiling. Stool samples will be collected for analysis of gut microbiota.\n\nA subset of participants will undergo skeletal muscle biopsies of the vastus lateralis at baseline and after the intervention. Muscle samples will be used to assess mitochondrial oxidative phosphorylation capacity, mitochondrial quality-control proteins, muscle fibre morphology, cell-type-specific transcriptomic profiles using single-nucleus RNA sequencing, and chromatin accessibility using ATAC-seq.\n\nThe study will provide an integrated assessment of the effects of resistance training on mitochondrial function, skeletal muscle biology, physical function, frailty, circulating biomarkers, and gut microbiota. These findings may help clarify the biological mechanisms through which resistance training influences muscle health and resilience during ageing and in older adults with T2DM.",[147,148,149,150],"Diabetes Type 2","Frail Elderly Syndrome","Mitochondrial Function, Bioenergetics","Functionality",[152,153,154,155,156],"Diabetes type 2","Frailty","Mitochondrial function","Skeletal Muscle","Physical Function","2026-09-14",{"date":159,"type":160},"2026-09-18","ACTUAL",{"date":162,"type":160},"2022-01-29",{"date":164,"type":141},"2028-07-31",{"name":5,"class":6},1]