Ignite Creation Date:
2024-05-05 @ 5:06 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00387712
Status:
COMPLETED
Last Update Posted:
2017-09-14
First Post:
2006-10-12
Brief Title:
Inflammatory Abnormalities in Muscle After Stroke Effects of Exercise
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Inflammatory Abnormalities in Muscle After Stroke Effects of Exercise
Status:
COMPLETED
Status Verified Date:
2017-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to first define whether abnormalities of skeletal muscle are related to the presence of inflammation and to poor motor performance and whether this can be modified by exercise interventions
Detailed Description:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None