Ignite Creation Date:
2024-05-06 @ 8:13 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06298201
Status:
RECRUITING
Last Update Posted:
2024-03-07
First Post:
2024-02-20
Brief Title:
E-Based Physical Exercise in Patients With Multiple Sclerosis and Comorbidity
Sponsor:
University of Southern Denmark
Organization:
University of Southern Denmark
Study Overview
Official Title:
Investigating of Effects of e-Based Physical Exercise in Patients With Multiple Sclerosis and Comorbidity
Status:
RECRUITING
Status Verified Date:
2024-02
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:
COMPACT
Brief Summary:
Background Physical exercise PE improves symptoms and quality of life in patients with multiple sclerosis pwMS Comorbidity is prevalent among pwMS and may contribute to disease progression Integrating and sustaining PE is challenging and E-based PE solutions have been proposed as a tool to support the integration of PE into daily life
Aims To assess the effect of e-based PE in addition to usual care in pwMS on clinical outcome and the levels of inflammatory metabolic and neurodegenerative mediators Furthermore to determine whether PE plays a role in the modification of comorbidities with a focus on vascular comorbidity and related risk factors ie type 2 diabetes mellitus
Method This study will be prospective with longitudinal follow-up of pwMS with and without comorbidities The physical activity of pwMS will be measured at baseline and after six months by accelerometers In a randomized controlled trial RCT patients will be randomly assigned in a 11 ratio to receive either usual care or usual care plus an e-based PE program The exercise program consists of resistance training with resistance bands targeting the lower extremities including leg press knee extension hip flexion hamstring curl and hip extension The sessions will enable participants to engage in group exercises from their homes through a secure online platform supervised virtually by physiotherapists The primary endpoints are walking capacity using the 6-meter walk test and the NEDA-3 scale focusing on the absence of clinical relapses and disease progression as indicated by an increase in the Expanded Disability Status Scale score and the absence of new disease activity on MRI including new T2 lesions or enhancing lesions Secondary outcomes will encompass measures of quality of life and fatigue as well as levels of potential biomarkers like neurofilament light chain in blood and cerebrospinal fluid
Conclusion This study will contribute to the rehabilitation and improved quality of life of pwMS particularly of patients with comorbidities The potential for e-based PE at home to encourage sustained exercise engagement among pwMS will be evaluated offering a significant contribution to the field of digital healthcare solutions
Aims To assess the effect of e-based PE in addition to usual care in pwMS on clinical outcome and the levels of inflammatory metabolic and neurodegenerative mediators Furthermore to determine whether PE plays a role in the modification of comorbidities with a focus on vascular comorbidity and related risk factors ie type 2 diabetes mellitus
Method This study will be prospective with longitudinal follow-up of pwMS with and without comorbidities The physical activity of pwMS will be measured at baseline and after six months by accelerometers In a randomized controlled trial RCT patients will be randomly assigned in a 11 ratio to receive either usual care or usual care plus an e-based PE program The exercise program consists of resistance training with resistance bands targeting the lower extremities including leg press knee extension hip flexion hamstring curl and hip extension The sessions will enable participants to engage in group exercises from their homes through a secure online platform supervised virtually by physiotherapists The primary endpoints are walking capacity using the 6-meter walk test and the NEDA-3 scale focusing on the absence of clinical relapses and disease progression as indicated by an increase in the Expanded Disability Status Scale score and the absence of new disease activity on MRI including new T2 lesions or enhancing lesions Secondary outcomes will encompass measures of quality of life and fatigue as well as levels of potential biomarkers like neurofilament light chain in blood and cerebrospinal fluid
Conclusion This study will contribute to the rehabilitation and improved quality of life of pwMS particularly of patients with comorbidities The potential for e-based PE at home to encourage sustained exercise engagement among pwMS will be evaluated offering a significant contribution to the field of digital healthcare solutions
Detailed Description:
Background Multiple sclerosis MS is an inflammatory demyelinating disease of the central nervous system CNS MS is a potentially disabling disease and occurs as a consequence of immune attacks on myelin and nerve fibers and may lead to neuronal damage neurodegeneration and consequently to the clinical accumulation of neurological disability Over the last two decades the age-specific prevalence of people with MS pwMS has increased and aging may amplify the risk of comorbidities and conversion to a progressive disease course Emerging evidence underscores the high prevalence of comorbidity in pwMS evident even at the time of MS diagnosis Comorbidities can lead to delayed MS diagnosis accelerated disease progression and diminished efficacy and safety of MS treatments subsequently increasing mortality Vascular comorbidities in particular are prevalent among MS patients with risk factors including type 2 diabetes mellitus T2DM obesity hyperlipidemia and hypertension
Physical exercise PE is advocated as an effective treatment for at least 26 chronic diseases including MS In pwMS PE has been shown to positively modulate peripheral inflammatory markers such as Tumour Necrosis Factor alpha TNF alpha interferon-gamma Interleukin-4 interleukin-10 etc and to reduce the rate of relapse PE directly enhances muscle strength and cardiorespiratory fitness as well as walking speed endurance and balance in MS patients Furthermore reductions in fatigue symptoms of depression and improvements in cognitive dysfunction and quality of life have been associated with PE in MS patients
Despite the clear benefits of PE for MS patients a significant proportion drop out or fail to maintain an active lifestyle post-rehabilitation This tendency is a serious challenge for integrating and sustaining PE in the daily lives of individuals with MS Consequently the effectiveness of electronic health devices or digital healthcare tools in addressing the challenge remains an important area of interest The effectiveness of new technology in MS rehabilitation including telerehabilitation has shown promising results in improving fitness gait balance and upper limb function often equaling or exceeding traditional methods
It may be concluded that PE represents an effective therapeutic strategy for pwMS however further research is required to investigate PEs long-term impact on managing pwMS with comorbidities
Study design This protocol delineates a prospective longitudinal randomized controlled trial RCT aimed at evaluating the effects of an e-based PE intervention at home in addition to usual care on the disability progression of pwMS both as an independent factor and in the context of comorbid conditions Furthermore an aim is to assess associations between PE and levels of inflammatory metabolic and neurodegenerative mediators and as well as clinical status in pwMS with or without comorbidities
Participants The study will include pwMS with T2DM as a well-defined and frequently occurring comorbidity and pwMS without comorbidity In addition screening for vascular comorbidity and related risk factors as T2DM hypertension and hyperlipidemia will be performed The pwMS will be matched for age and gender as well as severity of disability Details about the initiation and cessation of disease-modifying therapies DMT will be collected
Blinding and Randomization procedure Patients will be randomized in a 11 ratio into groups receiving either usual care or usual care plus a 6-month e-Based PE program using blocks of 4 or 6 by computer-generated assignment process Patients in both groups will receive care as usual which consist of single group therapy supervised by a physiotherapist 1 time a week The extent of care the patient receives during the trial period will be registered Due to the nature of the intervention it is not feasible to blind participants or physiotherapists delivering the program Nonetheless to preserve the integrity of the trial outcome assessors researchers will remain blinded to the allocation of treatments throughout the study
Interventions The e-based exercise intervention comprises a 6-months home-based resistance training for the lower extremities conducted twice weekly The focus on the lower extremities is due to the marked impairment in muscle strength compared to the upper extremities in pwMS The intervention adapts the principles of two previous studies on supervised machine-based resistance training for MS patients which effectively improved walking performance The original protocol is modified e-delivery incorporating five exercises leg press knee extension hip flexion hamstring curl and hip extension-using resistance bands While resistance band training has been beneficial for the upper extremity in MS in home-based training programs its application to the lower extremity is to the best of our knowledge yet unproven
All 48 sessions will be conducted in virtual groups of 6-8 participants supervised by an experienced physiotherapist connected to the virtual group from an exercise facility at the hospital using a 65 wide screen with computer hardware The sessions will be hosted using Hospital-to-Citizen videoconference software
Participants will perform exercises with a fast concentric phase and a slow eccentric phase
Participants will initially receive both verbal and written instructions on using the online platform and have a one-on-one virtual session with the physiotherapist to test the setup Resistance bands will be provided post-randomization The sessions will be tested and proven feasible in a mixed-methods study in patients with chronic conditions Additionally a trial run will be conducted with a few patients with MS to optimize the procedure before the trial
The self-management and exercise therapy programs details including activities duration frequency and methodologies are documented following the Template for Intervention Description and Replication TIDieR and the Consensus on Exercise Reporting Template CERT
Comorbid conditions At the study outset comorbidity data including diagnosis dates characteristics and treatments will be extracted from patients medical records and supplemented by patient interviews as needed
Cognitive assessment Participants education level and hand preference will be assessed through interviews and cognitive functions will be evaluated using the Montreal Cognitive Assessment MoCA Quality of life will be measured using the European Quality of Life-5 Dimensions EQ-5D index and visual analog scale VAS a range of scores from 0-100 A higher score indicates greater pain intensity
Specimens Blood and cerebrospinal fluid CSF samples will be systematically collected at three key time points baseline prior to starting the exercise program 6 months upon completion of the program at 12 and 24 months All clinical and laboratory data derived from these samples will be analyzed while maintaining blinding to ensure unbiased assessment The markers of inflammation metabolism and neurodegeneration will be measured with sensitive assays
MRI Participants will undergo initial and final CNS MRI using a 3 Tesla system will include brain spinal cord and optic nerve imaging with sequences like 3D FLAIR T2 SPACE and T1 MPRAGE Advanced techniques like multi-parametric mapping and diffusion-weighted imaging will be employed for detailed CNS characterization focusing on changes related to MS and vascular comorbidities
Patient reported outcomes For assessing fatigue the short-form Neuro-QOL Fatigue Scale will be utilized to measure current levels of fatigue This scale provides a valuable insight into the impact of fatigue on the quality of life of participants Health-related quality of life assessed using the standardized 5-level EuroQol 5-dimensional questionnaire EQ-5D-5L Depression level was measured using the Personal Health Questionnaire Depression Scale PHQ-8
Outcome measures and assessment timeline Outcome measures will include the above-mentioned assessments scheduled for documentation at baseline 6 12 and 24 months
Walking capacity assessed by the Six-Minute Walk Test 6MWT unit meter higher numbers indicate better performance
Objective measurement of physical activity PA at baseline and study conclusion providing detailed data on PA patterns and intensities Two accelerometers ms2 will be used to measure PA in each participant who will wear two accelerometers attached to the skin with tape one on the front of their thigh and one on the non-dominant wrist Data will be analyzed by descriptions of daily- and weekly PA patterns and time spent on different activities with different intensity among participants before and after the intervention
Cognitive function evaluated using the Montreal Cognitive Assessment MoCA a 30-item cognitive screen higher numbers indicate better performance
Fatigue levels assessed using the short-form Neuro-QOL Fatigue Scale Units on a Scale expressed as T scores with a mean of 50 and SD of 10
Disability progression monitored by changes in the EDSS score a scoring system between 0 and 10 the greater the level the more disability from baseline
MRI new T2 lesionenhancing lesion
Number of MS Relapses
Adverse events as detailed in section below
Body Mass Index BMI weight height kgmeter2 blood pressure mmHg lipid profiles triglyceride mmoll HDLmmoll HDLmmoll LDLmmoll cholesterolmmoll fasting blood glucose mmoll and insulin levels mIUL glucose tolerance mmoll and insulin resistance Patients who require 1 unitkgday are considered to have insulin resistance
Primary outcomes We will evaluate walking capacity by 6MWT and the no evidence of disease activity NEDA-3 score which is characterized by three parameters lack of clinical relapses and disease progression measured by EDSS and absence of new disease activity on MRI new T2 lesionsenhancing lesion over a period of observation time
Secondary outcomes Secondary outcomes include quality-of-life MoCA and fatigue the short-form Neuro-QOL Fatigue Scale Neurofilament Light Chain NfL levels will be used as marker of neuronal injury unit pgml
Adverse events Adverse events AE will be systematically documented for both the intervention and the usual care group using a patient diary over the course of the 6-month period Patients will report any symptoms or pain experienced post-PE Both AE and serious adverse events SAE will be proactively registered at all follow-ups visits employing open-probe questioning to ensure comprehensive recording of all AEs Additionally patient medical records will be reviewed at the primary endpoint 6 months to identify any AEs that have occurred since enrollment AEs will be classified in accordance with the Food and Drug Administrations definition of an SAE The recording categorization and assessment of the severity of AEs will be conducted irrespective of presumed causality with study treatments These evaluations will be conducted at 3- 6- and 12-months post-intervention
Data management The data related to this study will be securely stored in the REDCap database system This approved electronic platforms is chosen for data collection and data storage to ensure that missing data are kept to a minimum and that privacy and confidentiality of personal data are maintained
Physical exercise PE is advocated as an effective treatment for at least 26 chronic diseases including MS In pwMS PE has been shown to positively modulate peripheral inflammatory markers such as Tumour Necrosis Factor alpha TNF alpha interferon-gamma Interleukin-4 interleukin-10 etc and to reduce the rate of relapse PE directly enhances muscle strength and cardiorespiratory fitness as well as walking speed endurance and balance in MS patients Furthermore reductions in fatigue symptoms of depression and improvements in cognitive dysfunction and quality of life have been associated with PE in MS patients
Despite the clear benefits of PE for MS patients a significant proportion drop out or fail to maintain an active lifestyle post-rehabilitation This tendency is a serious challenge for integrating and sustaining PE in the daily lives of individuals with MS Consequently the effectiveness of electronic health devices or digital healthcare tools in addressing the challenge remains an important area of interest The effectiveness of new technology in MS rehabilitation including telerehabilitation has shown promising results in improving fitness gait balance and upper limb function often equaling or exceeding traditional methods
It may be concluded that PE represents an effective therapeutic strategy for pwMS however further research is required to investigate PEs long-term impact on managing pwMS with comorbidities
Study design This protocol delineates a prospective longitudinal randomized controlled trial RCT aimed at evaluating the effects of an e-based PE intervention at home in addition to usual care on the disability progression of pwMS both as an independent factor and in the context of comorbid conditions Furthermore an aim is to assess associations between PE and levels of inflammatory metabolic and neurodegenerative mediators and as well as clinical status in pwMS with or without comorbidities
Participants The study will include pwMS with T2DM as a well-defined and frequently occurring comorbidity and pwMS without comorbidity In addition screening for vascular comorbidity and related risk factors as T2DM hypertension and hyperlipidemia will be performed The pwMS will be matched for age and gender as well as severity of disability Details about the initiation and cessation of disease-modifying therapies DMT will be collected
Blinding and Randomization procedure Patients will be randomized in a 11 ratio into groups receiving either usual care or usual care plus a 6-month e-Based PE program using blocks of 4 or 6 by computer-generated assignment process Patients in both groups will receive care as usual which consist of single group therapy supervised by a physiotherapist 1 time a week The extent of care the patient receives during the trial period will be registered Due to the nature of the intervention it is not feasible to blind participants or physiotherapists delivering the program Nonetheless to preserve the integrity of the trial outcome assessors researchers will remain blinded to the allocation of treatments throughout the study
Interventions The e-based exercise intervention comprises a 6-months home-based resistance training for the lower extremities conducted twice weekly The focus on the lower extremities is due to the marked impairment in muscle strength compared to the upper extremities in pwMS The intervention adapts the principles of two previous studies on supervised machine-based resistance training for MS patients which effectively improved walking performance The original protocol is modified e-delivery incorporating five exercises leg press knee extension hip flexion hamstring curl and hip extension-using resistance bands While resistance band training has been beneficial for the upper extremity in MS in home-based training programs its application to the lower extremity is to the best of our knowledge yet unproven
All 48 sessions will be conducted in virtual groups of 6-8 participants supervised by an experienced physiotherapist connected to the virtual group from an exercise facility at the hospital using a 65 wide screen with computer hardware The sessions will be hosted using Hospital-to-Citizen videoconference software
Participants will perform exercises with a fast concentric phase and a slow eccentric phase
Participants will initially receive both verbal and written instructions on using the online platform and have a one-on-one virtual session with the physiotherapist to test the setup Resistance bands will be provided post-randomization The sessions will be tested and proven feasible in a mixed-methods study in patients with chronic conditions Additionally a trial run will be conducted with a few patients with MS to optimize the procedure before the trial
The self-management and exercise therapy programs details including activities duration frequency and methodologies are documented following the Template for Intervention Description and Replication TIDieR and the Consensus on Exercise Reporting Template CERT
Comorbid conditions At the study outset comorbidity data including diagnosis dates characteristics and treatments will be extracted from patients medical records and supplemented by patient interviews as needed
Cognitive assessment Participants education level and hand preference will be assessed through interviews and cognitive functions will be evaluated using the Montreal Cognitive Assessment MoCA Quality of life will be measured using the European Quality of Life-5 Dimensions EQ-5D index and visual analog scale VAS a range of scores from 0-100 A higher score indicates greater pain intensity
Specimens Blood and cerebrospinal fluid CSF samples will be systematically collected at three key time points baseline prior to starting the exercise program 6 months upon completion of the program at 12 and 24 months All clinical and laboratory data derived from these samples will be analyzed while maintaining blinding to ensure unbiased assessment The markers of inflammation metabolism and neurodegeneration will be measured with sensitive assays
MRI Participants will undergo initial and final CNS MRI using a 3 Tesla system will include brain spinal cord and optic nerve imaging with sequences like 3D FLAIR T2 SPACE and T1 MPRAGE Advanced techniques like multi-parametric mapping and diffusion-weighted imaging will be employed for detailed CNS characterization focusing on changes related to MS and vascular comorbidities
Patient reported outcomes For assessing fatigue the short-form Neuro-QOL Fatigue Scale will be utilized to measure current levels of fatigue This scale provides a valuable insight into the impact of fatigue on the quality of life of participants Health-related quality of life assessed using the standardized 5-level EuroQol 5-dimensional questionnaire EQ-5D-5L Depression level was measured using the Personal Health Questionnaire Depression Scale PHQ-8
Outcome measures and assessment timeline Outcome measures will include the above-mentioned assessments scheduled for documentation at baseline 6 12 and 24 months
Walking capacity assessed by the Six-Minute Walk Test 6MWT unit meter higher numbers indicate better performance
Objective measurement of physical activity PA at baseline and study conclusion providing detailed data on PA patterns and intensities Two accelerometers ms2 will be used to measure PA in each participant who will wear two accelerometers attached to the skin with tape one on the front of their thigh and one on the non-dominant wrist Data will be analyzed by descriptions of daily- and weekly PA patterns and time spent on different activities with different intensity among participants before and after the intervention
Cognitive function evaluated using the Montreal Cognitive Assessment MoCA a 30-item cognitive screen higher numbers indicate better performance
Fatigue levels assessed using the short-form Neuro-QOL Fatigue Scale Units on a Scale expressed as T scores with a mean of 50 and SD of 10
Disability progression monitored by changes in the EDSS score a scoring system between 0 and 10 the greater the level the more disability from baseline
MRI new T2 lesionenhancing lesion
Number of MS Relapses
Adverse events as detailed in section below
Body Mass Index BMI weight height kgmeter2 blood pressure mmHg lipid profiles triglyceride mmoll HDLmmoll HDLmmoll LDLmmoll cholesterolmmoll fasting blood glucose mmoll and insulin levels mIUL glucose tolerance mmoll and insulin resistance Patients who require 1 unitkgday are considered to have insulin resistance
Primary outcomes We will evaluate walking capacity by 6MWT and the no evidence of disease activity NEDA-3 score which is characterized by three parameters lack of clinical relapses and disease progression measured by EDSS and absence of new disease activity on MRI new T2 lesionsenhancing lesion over a period of observation time
Secondary outcomes Secondary outcomes include quality-of-life MoCA and fatigue the short-form Neuro-QOL Fatigue Scale Neurofilament Light Chain NfL levels will be used as marker of neuronal injury unit pgml
Adverse events Adverse events AE will be systematically documented for both the intervention and the usual care group using a patient diary over the course of the 6-month period Patients will report any symptoms or pain experienced post-PE Both AE and serious adverse events SAE will be proactively registered at all follow-ups visits employing open-probe questioning to ensure comprehensive recording of all AEs Additionally patient medical records will be reviewed at the primary endpoint 6 months to identify any AEs that have occurred since enrollment AEs will be classified in accordance with the Food and Drug Administrations definition of an SAE The recording categorization and assessment of the severity of AEs will be conducted irrespective of presumed causality with study treatments These evaluations will be conducted at 3- 6- and 12-months post-intervention
Data management The data related to this study will be securely stored in the REDCap database system This approved electronic platforms is chosen for data collection and data storage to ensure that missing data are kept to a minimum and that privacy and confidentiality of personal data are maintained
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?:
None
Is an FDA AA801 Violation?:
None