Clinical trial NCT06436131: The Effects of In-phase Bilateral Exercise in People with Progressive Multiple Sclerosis
Official title: The Effects of In-phase Bilateral Exercise on Cognitive and Motor Outcome Measures, in Patients with Progressive Multiple Sclerosis, a Randomized Control Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis, Primary Progressive
Multiple Sclerosis, Secondary Progressive
Keywords: In-phase Bilateral
exercise
cognitive processing
multiple sclerosis
manual dexterity
Lead sponsor: Cyprus University of Technology
Sponsor class: OTHER
Collaborators: name: Cyprus Institute of Neurology and Genetics
First posted: 2024-05-30
Enrollment: 20
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects were randomized in two groups. Experimental group received an exercise program based on in-phase bilateral exercises, whereas the active control group receives conservative exercises. The duration of the study was 12 consecutive weeks for both groups.
Primary purpose: TREATMENT

Brief summary: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. MS, typical presents with progression of clinical symptoms which mainly include motor and cognitive impairment, as well as reduction of patients' quality of life. Exercise is an effective approach in the management of the symptoms in people with progressive MS. Previous studies in healthy and in people with MS, reported a close relationship between cognitive functions and upper limb performance. Since patients with progressive MS facing difficulties with performing complex exercises due to cognitive dysfunctions and given the close relationship between cognitive functions and manual dexterity, a reasonable question arises whether a type of upper limbs exercises with less cognitive demands will improve the information processing speed in people with progressive MS. The aim of the current study is to investigate the effects of in-phase bilateral upper limbs exercises on the information processing speed, in patients with progressive MS, given that in-phase bilateral movements needs less attentional load than the other types of bilateral coordination. The intervention protocol lasted for 12 consecutive weeks (30-60 minutes /session x 3 sessions/week) and included in-phase bilateral exercises of the upper limbs, adapted to different sports activities and to functional training. Results from the statistical analysis indicated improvement of the experimental group compared to the control group, on the information processing speed alongside with improvement of motor skills.

Detailed description: The term progressive multiple sclerosis (MS) includes both secondary progressive MS (SPMS) and primary progressive MS (PPMS). As it is well known, the course of MS is highly variable. On one hand, almost 50% of the patients who is characterized by the relapsing remitting MS, after 10-15 years of disease this pattern becomes progressive, in which individual clinical symptoms slowly progress, a disease type defined as a SPMS. On the other hand, in about 15% of people with MS, disease progression is persistent from onset defined as a PPMS. Patients with progressive MS except from physical impairment, often have cognitive dysfunctions, which negatively affect quality of life. Information processing speed is the most common cognitive deficit, between people with PPMS and those with SPMS.

Despite the fact that cognitive rehabilitation approaches are effective in treating MS-related cognitive dysfunctions, there are evidence from several studies which indicated the impact of different types of exercises in the improvement of cognitive in people with MS. Furthermore, evidences from previous studies in healthy and people with MS, reported a close relationship between cognitive functions and upper limbs performance, defined by the projections from the Anterior Cingulate Cortex to the motor cortex and spinal cord. Specifically, the decline of information processing speed indicates reduction of manual dexterity in people with MS. Manual dexterity is defined as the manual skill which contains coordination of fine and gross voluntary movements of the upper limbs. Manual dexterity dysfunction in MS contributes to reduced ability to perform activities of daily living (ADLs) and social activities, which causes reduction of independency and quality of life.

Moreover, evidence from previous studies, reported that in-phase bilateral movements needs less attentional load and less neural control than the unilateral or the other types of bilateral coordination, as a result to perform the specific type of movement (i.e., in-phase bilateral) more efficient and more easy. Therefore, given that patients with progressive MS characterized by decline of information processing speed, which affects manual dexterity, a reasonable question arises whether in-phase bilateral upper limbs exercises will improve information processing speed and thus, to improve manual dexterity in the specific clinical cohort.

The aim of the current study was to investigate primarily the hypothesis that a 12-week exercise program based on in-phase bilateral upper limbs movements, based on sport activities and functional training, could improve information processing speed compared to a conservative type of exercise, in people with progressive MS. A secondary aim was to evaluate whether the specific exercise program could improve manual dexterity and have a correlation with information processing speed.

Second aim of the study was to investigate the effects of the specific type of exercises on various clinical symptoms, fatigue and on quality of life, using clinical assessment tools and subjective questionnaires.

Eligibility criteria: Inclusion Criteria:

* diagnosis of progressive multiple sclerosis (MS) (primary or/and secondary progressive MS)
* Expanded Disability Status Scale score between three and six
* no relapse within 30 days
* aged between 30 and 70 years
* Mini Mental State of Examination score between 20 and 30 (mild to no cognitive impairment)

Exclusion Criteria:

* history of any disease affecting the central nervous system other than MS (e.g., stroke, Parkinson's disease, cerebral palsy)
* history of cardiovascular disease (e.g., known aneurism, myocardial infarction, hyper/hypotension, heart failure)
* severe orthopaedic disorders (e.g., knee or hip replacement, spondylosurgery, disk herniation, recent bone fracture)
* mental disorders (e.g., depression, schizophrenia, bipolar syndrome)
* pregnancy during the implementation of the study timeline
* hearing impairments (i.e., deafness)
* visual deficit (e.g., optic neuritis, blindness, diplopia, glaucoma, blurred vision)
* history of epileptic seizures
* spasticity level on upper or lower limbs more than 1+ (slight increase in muscle tone) according to Modified Ashworth Scale

Primary outcomes:
measure: Symbol Digit Modalities Test
timeFrame: Baseline (3 weeks) until the end of the Intervention (12 weeks)
Secondary outcomes:
measure: Medical Outcomes Study Short Form 36
timeFrame: Baseline (3rd week) until the end of the Intervention (12 weeks)
measure: Modified Fatigue Impact Scale
timeFrame: Baseline (3rd week) until the end of the Intervention (12 weeks)
measure: Trail Making Test
timeFrame: Baseline (3 weeks) until the end of the Intervention (12 weeks)
measure: Purdue Pegboard Test
timeFrame: Baseline (3 weeks) until the end of the Intervention (12 weeks)
measure: Timed 25-Foot Walk
timeFrame: Baseline (3 weeks) until the end of the Intervention (12 weeks)
measure: Six Spot Step Test
timeFrame: Baseline (3 weeks) until the end of the Intervention (12 weeks)
Other outcomes:
Locations:
city: Limassol
country: Cyprus
facility: Dimitris Sokratous
Study officials:
affiliation: Cyprus University of Technology
name: Dimitris Sokratous
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Sokratous D, Charalambous CC, Papanicolaou EZ, Michailidou K, Konstantinou N. Investigation of in-phase bilateral exercise effects on corticospinal plasticity in relapsing remitting multiple sclerosis: A registered report single-case concurrent multiple baseline design across five subjects. PLoS One. 2023 Mar 2;18(3):e0272114. doi: 10.1371/journal.pone.0272114. eCollection 2023.