Ignite Creation Date:
2024-05-06 @ 1:49 PM
Last Modification Date:
2024-10-26 @ 1:20 PM
Study NCT ID:
NCT04135391
Status:
COMPLETED
Last Update Posted:
2019-10-22
First Post:
2019-10-20
Brief Title:
Aerobic Trainings on Stroke Patients
Sponsor:
Chang Gung Memorial Hospital
Organization:
Chang Gung Memorial Hospital
Study Overview
Official Title:
Effects of Aerobic Interval Exercise Training on Cardiac Fibroblasts and Brain Cells in Stroke Patients
Status:
COMPLETED
Status Verified Date:
2019-07
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:
Effects of different exercise strategies on stroke patients remain unclear Randomized controlled trial with concealed allocation has been performed from August 1 2016 to June 30 2018 We traced back 23 stroke patients recruited during the above period aged about 55 years with stroke duration 24 months Intervention 13 of them underwent 36 times of moderate-intensity continuous training MICT at 60 of peak oxygen consumption VO2peak for 30 mins and 10 had high-intensity interval training HIIT at alternative 80 and 40 VO2peak with the same training times and duration Outcome measures VO2peak cardiac output CO bilateral frontal cortex blood volume THb oxyhemoglobin O2Hb and deoxyhemoglobin HHb ventilation efficiency serum brain-derived neurotrophic factor BDNF levels cognitive and life quality questionnaire percentage of neuroblastic cell bearing neurites neurites and cell fluorescent staining were examined before and after interventions
Detailed Description:
Design The Institutional Review Board of a tertiary care hospital approved the study IRB No 201600576A3 A randomized controlled trial was performed in stroke patients with different exercise regimens and was blind to the assessors The study was conducted from August 2016 to June 2018 Participants were randomly allocated to the MICT or HIIT groups using a computer-generated concealed allocation schedule All included stroke patients received traditional rehabilitation programs including balance range of motion or therapeutic exercise and additional in-hospital supervised 30 min of MICT or HIIT for 36 times Data were collected by a blinded assessor prior to randomization after completing the exercise trainings
Participants Stroke patients diagnosed by the neurologist were surveyed The inclusion criteria were listed as follows I 20 years old II stroke events with stable clinical status 3 months III mini-mental state examination MMSE 24 IV no acute coronary syndrome Those who had unstable angina systolic blood pressure 200 mmHg or diastolic blood pressure 110 mm Hg symptomatic orthostatic hypotension severe aortic stenosis peak systolic pressure gradient 50 mmHg or an aortic valve opening area 075 cm2 inflammatory disease within recent 3 months uncontrolled cardiac dysrhythmias uncompensated HF third degree atrioventricular block pericarditis or myocarditis within recent 3 months embolic disease within recent 3 months ST segment displacement 2 mm at rest and uncontrolled diabetes blood glucose 300 mgdL or 250 mgdL with ketone bodies were not candidates of the study
Stroke patients had absolute contraindications for cardiopulmonary exercise test CPET and aerobic activities suggested by the American College of Sports Medicine ACSM were also excluded in the study Afterwards eligible participants were randomly assigned to the MICT and HIIT groups Baseline demographic characteristics were also recorded All subjects provided informed consent after the experimental procedures were explained
Cardiopulmonary exercise test CPET Participants underwent an incremental exercise test on a bicycle ergometer Ergoselect 150P ergoline GmbH Bitz Germany and the examination was performed at a work-rate of 10 Wmin with continuous monitoring heart rate brachial blood pressure and arterial oxygen saturation until the stop conditions described previously Oxygen consumption VO2 was measured by a cardiopulmonary measurement device MasterScreen CPX CareFusion Corp Hoechberg Germany The VO2peak minute ventilation VE and carbon dioxide production VCO2 were defined as the guideline for exercise testing suggested by the ACSM VE and VCO2 responses acquired from the initiation of exercise to the peak values were used to calculate the VE-VCO2 slope using the least-square linear regression The O2 uptake efficiency slope OUES an estimation of the O2 consumption efficiency during exercise was derived from the slope of a natural logarithm plot of VE vs VO2
Cardiac hemodynamic measurements Noninvasive continuous cardiac output monitoring system NICOM Cheetah Medical Wilmington Delaware was used to evaluate cardiac hemodynamic response to exercise which analyzes the phase shift ΔΦ created by alternating electrical current across the chest of the subject as described in our previous study
Cerebral hemodynamic measurements Two pairs of near infra-red spectroscopy NIRS probes Oxymon Artinis The Netherland were attached to bilateral frontal areas of each included subject during CPET The Beer-Lambert law was applied to measure light absorption across each pair of NIRS detectors reflecting changes of oxyhemoglobin O2Hb and deoxyhemoglobin HHb in the frontal cortex during exercise Total Hb amount THb was calculated as the sum of O2Hb and HHb and was used as an index of change in blood volume in the frontal cortex Differences of the tissue oxygenation ΔO2Hb and ΔHHb and regional blood flow ΔTHb between involved and uninvolved frontal cortices involved-uninvolved were used to estimate effects of different exercise regimens on brain tissue oxygenation and regional blood flow
Health-related QoL QoL was measured by the Short Form-36 Health Survey questionnaire SF-36 and mini-mental status examination MMSE was used to assess QoL and cognitive functions of the participants
Exercise training protocols The included subjects underwent 36 times of supervised hospital-based training 2-3 sessionweek on a bicycle ergometer Ergoselect 150P Germany as our previous protocol15 The training comprised a warm-up at 30 of VO2peak for 3 min followed by a MICT 60 of VO2peak or HIIT five 3-min intervals at 80 of VO2peak and each interval separated by 3-min exercise at 40 of VO2peak for 30 min and then a cool-down at 30 of VO2peak for 3 min The training was terminated when the subject had symptomssigns suggested by the ACSM guideline
Serum preparation An amount of 20 ml fresh blood was collected from all our subjects before and after exercise training Samples were centrifuged at 2500 rpm for 5 min at room temperature and the upper serum was preserved for cell culture and measurement of serum BDNF levels
Measurement of serum BDNF BDNF levels were assessed before and after aerobic exercise trainings Prepared serum of 100 µL was added in each well coated with the human BDNF capture antibody in a solid-phase sandwich two-site enzyme linked immunoassay ELISA kit BioVision Inc Milpitas CA The BDNF level was then determined by the microplate reader SpectraMax M3 Molecular Devices LLC San Jose CA
Cell culture and neurite growth assay Rat neuroblastic cells PC-12 cell line were grown in Dulbeccos modified Eagles medium DMEM supplemented with 75 patient serum before and after exercise training 75 horse serum HS 100 unitsml penicillin and 100 mgL streptomycin
A total of 100000 cells were plated overnight on 35-mm dishes coated with poly- DL-lysine After serum starvation in DMEM containing 2 HS for 12-18 h cells were treated with 50 ngml NGF for the indicated time Morphological changes were observed using the Leica TCS SP8 confocal microscopy 7 days after cultured with patient sera before and after exercise training Percentage of cells with neurites of at least one cell body diameter in length was determined in five independent fields of every plate
Fluorescent stains Cells 100000 were inoculated in each well of the eight-chamber slide Millicell EZ slide Millipore Corp Billerica MA and were incubated at the pre- and post-MICT or HIIT sera for 12h Vivid staining of Mitotracker Invitrogen corp Carlsbad CA was used to observe mitochondria in neuroblastic cells treated with sera from the above different status The cells were stained with primary rabbit monoclonal anti--tubulin antibodies Cell Signaling Technology Inc Boston MA Fluorescein isothiocyanate-conjugated AffiniPure Goat anti-rabbit IgG Jackson ImmunoResearch Laboratories West Grove PA was used as the secondary antibody Nuclei were counterstained with mounting medium Vector Laboratories Inc Burlingame CA containing 406-diamidino-2-phenylindole The stained cells were examined with a confocal microscopic examination Leica TCS SP8 Leica Microsystems Inc Buffalo Grove IL
Statistical analysis Chi-square test was conducted to compare differences of non-parametric parameters between the two groups Mann-Whitney U test was used to assess differences of age stroke duration body mass index BMI changes of exercise capacity changes of brain oxygenation as well as regional blood volume changes of BDNF levels and changes of cell behaviors between the two groups Differences of within group changes in numerical data was assessed by Wilcoxon matched-pair signed-rank test Relationships between changes of measured clinical parameters after the exercise training and clinical information were analyzed by Pearson correlation A p value 005 was considered as statistical significance
Participants Stroke patients diagnosed by the neurologist were surveyed The inclusion criteria were listed as follows I 20 years old II stroke events with stable clinical status 3 months III mini-mental state examination MMSE 24 IV no acute coronary syndrome Those who had unstable angina systolic blood pressure 200 mmHg or diastolic blood pressure 110 mm Hg symptomatic orthostatic hypotension severe aortic stenosis peak systolic pressure gradient 50 mmHg or an aortic valve opening area 075 cm2 inflammatory disease within recent 3 months uncontrolled cardiac dysrhythmias uncompensated HF third degree atrioventricular block pericarditis or myocarditis within recent 3 months embolic disease within recent 3 months ST segment displacement 2 mm at rest and uncontrolled diabetes blood glucose 300 mgdL or 250 mgdL with ketone bodies were not candidates of the study
Stroke patients had absolute contraindications for cardiopulmonary exercise test CPET and aerobic activities suggested by the American College of Sports Medicine ACSM were also excluded in the study Afterwards eligible participants were randomly assigned to the MICT and HIIT groups Baseline demographic characteristics were also recorded All subjects provided informed consent after the experimental procedures were explained
Cardiopulmonary exercise test CPET Participants underwent an incremental exercise test on a bicycle ergometer Ergoselect 150P ergoline GmbH Bitz Germany and the examination was performed at a work-rate of 10 Wmin with continuous monitoring heart rate brachial blood pressure and arterial oxygen saturation until the stop conditions described previously Oxygen consumption VO2 was measured by a cardiopulmonary measurement device MasterScreen CPX CareFusion Corp Hoechberg Germany The VO2peak minute ventilation VE and carbon dioxide production VCO2 were defined as the guideline for exercise testing suggested by the ACSM VE and VCO2 responses acquired from the initiation of exercise to the peak values were used to calculate the VE-VCO2 slope using the least-square linear regression The O2 uptake efficiency slope OUES an estimation of the O2 consumption efficiency during exercise was derived from the slope of a natural logarithm plot of VE vs VO2
Cardiac hemodynamic measurements Noninvasive continuous cardiac output monitoring system NICOM Cheetah Medical Wilmington Delaware was used to evaluate cardiac hemodynamic response to exercise which analyzes the phase shift ΔΦ created by alternating electrical current across the chest of the subject as described in our previous study
Cerebral hemodynamic measurements Two pairs of near infra-red spectroscopy NIRS probes Oxymon Artinis The Netherland were attached to bilateral frontal areas of each included subject during CPET The Beer-Lambert law was applied to measure light absorption across each pair of NIRS detectors reflecting changes of oxyhemoglobin O2Hb and deoxyhemoglobin HHb in the frontal cortex during exercise Total Hb amount THb was calculated as the sum of O2Hb and HHb and was used as an index of change in blood volume in the frontal cortex Differences of the tissue oxygenation ΔO2Hb and ΔHHb and regional blood flow ΔTHb between involved and uninvolved frontal cortices involved-uninvolved were used to estimate effects of different exercise regimens on brain tissue oxygenation and regional blood flow
Health-related QoL QoL was measured by the Short Form-36 Health Survey questionnaire SF-36 and mini-mental status examination MMSE was used to assess QoL and cognitive functions of the participants
Exercise training protocols The included subjects underwent 36 times of supervised hospital-based training 2-3 sessionweek on a bicycle ergometer Ergoselect 150P Germany as our previous protocol15 The training comprised a warm-up at 30 of VO2peak for 3 min followed by a MICT 60 of VO2peak or HIIT five 3-min intervals at 80 of VO2peak and each interval separated by 3-min exercise at 40 of VO2peak for 30 min and then a cool-down at 30 of VO2peak for 3 min The training was terminated when the subject had symptomssigns suggested by the ACSM guideline
Serum preparation An amount of 20 ml fresh blood was collected from all our subjects before and after exercise training Samples were centrifuged at 2500 rpm for 5 min at room temperature and the upper serum was preserved for cell culture and measurement of serum BDNF levels
Measurement of serum BDNF BDNF levels were assessed before and after aerobic exercise trainings Prepared serum of 100 µL was added in each well coated with the human BDNF capture antibody in a solid-phase sandwich two-site enzyme linked immunoassay ELISA kit BioVision Inc Milpitas CA The BDNF level was then determined by the microplate reader SpectraMax M3 Molecular Devices LLC San Jose CA
Cell culture and neurite growth assay Rat neuroblastic cells PC-12 cell line were grown in Dulbeccos modified Eagles medium DMEM supplemented with 75 patient serum before and after exercise training 75 horse serum HS 100 unitsml penicillin and 100 mgL streptomycin
A total of 100000 cells were plated overnight on 35-mm dishes coated with poly- DL-lysine After serum starvation in DMEM containing 2 HS for 12-18 h cells were treated with 50 ngml NGF for the indicated time Morphological changes were observed using the Leica TCS SP8 confocal microscopy 7 days after cultured with patient sera before and after exercise training Percentage of cells with neurites of at least one cell body diameter in length was determined in five independent fields of every plate
Fluorescent stains Cells 100000 were inoculated in each well of the eight-chamber slide Millicell EZ slide Millipore Corp Billerica MA and were incubated at the pre- and post-MICT or HIIT sera for 12h Vivid staining of Mitotracker Invitrogen corp Carlsbad CA was used to observe mitochondria in neuroblastic cells treated with sera from the above different status The cells were stained with primary rabbit monoclonal anti--tubulin antibodies Cell Signaling Technology Inc Boston MA Fluorescein isothiocyanate-conjugated AffiniPure Goat anti-rabbit IgG Jackson ImmunoResearch Laboratories West Grove PA was used as the secondary antibody Nuclei were counterstained with mounting medium Vector Laboratories Inc Burlingame CA containing 406-diamidino-2-phenylindole The stained cells were examined with a confocal microscopic examination Leica TCS SP8 Leica Microsystems Inc Buffalo Grove IL
Statistical analysis Chi-square test was conducted to compare differences of non-parametric parameters between the two groups Mann-Whitney U test was used to assess differences of age stroke duration body mass index BMI changes of exercise capacity changes of brain oxygenation as well as regional blood volume changes of BDNF levels and changes of cell behaviors between the two groups Differences of within group changes in numerical data was assessed by Wilcoxon matched-pair signed-rank test Relationships between changes of measured clinical parameters after the exercise training and clinical information were analyzed by Pearson correlation A p value 005 was considered as statistical significance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None