Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06298201 |
| Other study ID # |
IMAGINE2024 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 2024 |
| Est. completion date |
July 2025 |
Study information
| Verified date |
February 2024 |
| Source |
University of Southern Denmark |
| Contact |
Nasrin Asgari, Professor |
| Phone |
+4530700612 |
| Email |
nasgari[@]health.sdu.dk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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, i.e., 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 1:1 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.
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 PE's 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 1:1 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 program's 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 (m/s2) 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 lesion/enhancing lesion
- Number of MS Relapse(s)
- Adverse events (as detailed in section below)
- Body Mass Index (BMI) (weight /height, kg/meter2), blood pressure (mmHg), lipid profiles
(triglyceride (mmol/l), HDL(mmol/l, HDL(mmol/l), , LDL(mmol/l), cholesterol(mmol/l),),
fasting blood glucose (mmol/l), and insulin levels (mIU/L), glucose tolerance (mmol/l),
and insulin resistance (Patients who require >1 unit/kg/day 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 lesions/enhancing 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 pg/ml.
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-up's 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
Administration's 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.
