- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00387712
Inflammatory Abnormalities in Muscle After Stroke: Effects of Exercise
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Stroke is the leading cause of disability in the United States. Biological changes in hemiparetic skeletal muscle may further propagate the disability. The investigators report gross muscular atrophy and major shift to fast myosin heavy chain (MHC) isoform distribution in hemiparetic thigh that are related to reduced fitness and slow walking speed. The investigators also find elevated inflammatory mediators, tumor necrosis factor (TNF) and nuclear factor kappa beta (NFkB) in the paretic thigh muscle. No prior studies have systematically examined the profile of hemiparetic muscle contractile proteins and their relationship to function and fitness after stroke. Furthermore, the molecular mechanisms underlying hemiparetic skeletal muscle atrophy and contractile protein abnormalities are unknown.
The investigators have investigated treadmill aerobic exercise (T-AEX), as a task-oriented training model. This exercise model can reverse the alterations in MHC profile in hemiparetic leg muscles after stroke. This T-AEX program also improves fitness (VO2) levels, leg strength, and ambulatory performance in chronic stroke. Moreover, post hoc analyses our randomized treadmill exercise program show that specific features of the exercise prescription likely influence the nature of exercise-mediated adaptations.
Hypothesis: The investigators propose a randomized clinical study to investigate the hypothesis that in chronic stroke patients a 6 month velocity-based progressive T-AEX program is superior to duration-based progressive T-AEX for improving hemiparetic (HP) leg skeletal muscle contractile protein expression and reducing inflammatory markers to improve muscle function, fitness, and ambulation.
Specific Aims: 1) Determine whether skeletal muscle MHC isoform expression is altered and inflammatory mediators, TNF and markers of NFkB activation, present in the hemiparetic vastus lateralis muscle, compared the non-paretic leg and matched non-stroke control leg muscles, and related to muscle function, fitness, and gait performance. 2) Determine whether 6 months progressive T-AEX programs can attenuate this abnormal MHC profile and inflammatory mediators to improve muscle structure and function.
Methods: At baseline, bilateral vastus lateralis (VL) biopsies are obtained from chronically disabled, stroke participants with hemiparetic gait to examine the HP and non-P thigh skeletal muscles for alterations in MHC isoforms, key muscle contractile protein, and evidence for inflammation (TNFa) and NFkB activation. Participants are randomized to 6 months of progressive velocity-based or duration-based T-AEX training. Repeat VL muscle biopsies are obtained in the HP limb only after exercise interventions to assess whether 6-month exercise rehabilitation can restore MHC profile and attenuate activation of inflammatory pathways. Expression of the specific MHC isoforms, TNF, and NFKB marker expression (mRNA and protein) are investigated in these muscle tissues by real-time real time (RT)- polymerase chain reaction (PCR), Western Blot analysis, and immunohistochemistry. The investigators will explore relationships between T-AEX mediated changes in MHC expression and inflammatory activation in skeletal muscle after stroke to improve muscle strength, muscle performance, fitness and activity levels, activities of daily living (ADL) performance, and gait deficit severity.
Anticipated Results and Relevance: The cross-sectional baseline data will provide the first systematic study of a substantial cohort of stroke patients to define the relationship between altered structural and contractile protein expression to both muscle physiology and clinical measures of muscle performance, metabolic fitness, and rehabilitation mobility outcomes. HP VL muscle will be directly compared to the non-paretic (NP) limb muscle within-subjects and to non-stroke reference controls, in order to better understand the scope of skeletal muscle inflammatory and metabolic abnormalities in the stroke population. The intervention results will allow us to determine the specific requirements of treadmill training that are optimal and crucial to produce the exercise-mediated adaptations in hemiparetic skeletal muscle that lead to improved rehabilitation outcomes to reduce the disability of chronic stroke.
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
-
-
Maryland
-
Baltimore, Maryland, Estados Unidos, 21201
- VA Maryland Health Care System, Baltimore
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Chronic stroke (>6 months after initial stroke)
- Age 40-80
- Stable neurologic deficits
- Able to walk with an assistive device
- Language skills to understand the training program safely
Exclusion Criteria:
- No anticoagulation or medical conditions that preclude exercise.
- No dementias or depression
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
---|---|
Experimental: Velocity based treadmill training
6 month of progressive treadmill walking with treadmill speed gradually progressed to meet the training heart rate goals for moderate intensity aerobic exercise, when hemiparetic gait velocity can no longer be safely progressed, incline is added to achieve the heart rate training goals.
|
6 month of progressive treadmill walking with a safety harness and hand rail support to prevent falls.
Treadmill speed is gradually progressed to meet the training heart rate goals for moderate aerobic exercise, when hemiparetic gait velocity can no longer be progressed, incline is added to achieve heart rate training goals.
Progression is also based on participant's tolerance, abilities and safety.
|
Experimental: Duration based treadmill training
6 month of progressive treadmill walking with duration is gradually progressed to meet the endurance goals for low aerobic intensity exercise, gait velocity and incline do not progress.
|
6 month of progressive treadmill walking with a safety harness and hand rail support to prevent falls.
Treadmill duration is gradually progressed to meet the endurance goals for low aerobic intensity exercise, gait velocity and incline do not progress.
Progression is based on participant's tolerance, abilities and safety.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Cardiovascular Fitness (VO2 Peak)
Prazo: Baseline to 6 month
|
Cardiovascular fitness is measured by collecting the expired gases during a progressive graded treadmill test.
|
Baseline to 6 month
|
Paretic Thigh Skeletal Muscle Myosin Heavy Chain Myosin Heavy Chain Isoform 2a
Prazo: Baseline to 6 month
|
Skeletal muscle punch biopsies are obtained from the bilateral (paretic and non-paretic) vastus lateralis thigh muscle, at baseline and after 6 month interventions.
Homogenized muscle messenger ribonucleic acid (mRNA) for myosin heavy chain isoforms are analyzed by real time polymerase chain reaction as fluorescent units with normalization to an acidic ribosomal protein, a housekeeping gene.
|
Baseline to 6 month
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
30 Foot Walk Time (Sec)
Prazo: baseline to 6 month
|
Participants are instructed to walk fast as comfortable on a straight pathway on the floor demarcated by cones.
They may use their usual canes, walkers, and orthotics while they walk.
The walks are timed, the value is the mean of three trials with an interval rest between each trial.
|
baseline to 6 month
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Charlene Hafer-Macko, MD, VA Maryland Health Care System, Baltimore
Publicações e links úteis
Publicações Gerais
- Ivey FM, Ryan AS, Hafer-Macko CE, Macko RF. Improved cerebral vasomotor reactivity after exercise training in hemiparetic stroke survivors. Stroke. 2011 Jul;42(7):1994-2000. doi: 10.1161/STROKEAHA.110.607879. Epub 2011 Jun 2.
- Ivey FM, Hafer-Macko CE, Macko RF. Exercise training for cardiometabolic adaptation after stroke. J Cardiopulm Rehabil Prev. 2008 Jan-Feb;28(1):2-11. doi: 10.1097/01.HCR.0000311501.57022.a8.
- Ivey FM, Hafer-Macko CE, Macko RF. Task-oriented treadmill exercise training in chronic hemiparetic stroke. J Rehabil Res Dev. 2008;45(2):249-59. doi: 10.1682/jrrd.2007.02.0035.
- Prior SJ, McKenzie MJ, Joseph LJ, Ivey FM, Macko RF, Hafer-Macko CE, Ryan AS. Reduced skeletal muscle capillarization and glucose intolerance. Microcirculation. 2009 Apr;16(3):203-12. doi: 10.1080/10739680802502423. Epub 2009 Feb 16.
- McKenzie MJ, Yu S, Macko RF, McLenithan JC, Hafer-Macko CE. Human genome comparison of paretic and nonparetic vastus lateralis muscle in patients with hemiparetic stroke. J Rehabil Res Dev. 2008;45(2):273-81. doi: 10.1682/jrrd.2007.02.0036.
- Ryan AS, Ivey FM, Prior S, Li G, Hafer-Macko C. Skeletal muscle hypertrophy and muscle myostatin reduction after resistive training in stroke survivors. Stroke. 2011 Feb;42(2):416-20. doi: 10.1161/STROKEAHA.110.602441. Epub 2010 Dec 16.
- Hafer-Macko CE, Ryan AS, Ivey FM, Macko RF. Skeletal muscle changes after hemiparetic stroke and potential beneficial effects of exercise intervention strategies. J Rehabil Res Dev. 2008;45(2):261-72. doi: 10.1682/jrrd.2007.02.0040.
- Ryan AS, Buscemi A, Forrester L, Hafer-Macko CE, Ivey FM. Atrophy and intramuscular fat in specific muscles of the thigh: associated weakness and hyperinsulinemia in stroke survivors. Neurorehabil Neural Repair. 2011 Nov-Dec;25(9):865-72. doi: 10.1177/1545968311408920. Epub 2011 Jul 6.
- Ivey FM, Stookey AD, Hafer-Macko CE, Ryan AS, Macko RF. Higher Treadmill Training Intensity to Address Functional Aerobic Impairment after Stroke. J Stroke Cerebrovasc Dis. 2015 Nov;24(11):2539-46. doi: 10.1016/j.jstrokecerebrovasdis.2015.07.002. Epub 2015 Aug 21.
Links úteis
- Click here for more information about this study: Inflammatory Abnormalities in Muscle After Stroke: Effects of Exercise
- Click here for more information about this study: Inflammatory Abnormalities in Muscle After Stroke: Effects of Exercise
- Click here for more information about this study: Inflammatory Abnormalities in Muscle After Stroke: Effects of Exercise
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- B3834-R
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .