Multiple Sclerosis, Mitochondrial Alteration
Conditions
Brief summary
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and is one of the most common neurological diseases, often leading to disability of the patients. The MS pathogenesis includes vascular and inflammatory components, however recently also the role of mitochondrial dysfunction being a hot topic in neurodegeneration.
Detailed description
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and is one of the most common neurological diseases, often leading to disability of the patients. The MS pathogenesis includes vascular and inflammatory components, however recently also the role of mitochondrial dysfunction being a hot topic in neurodegeneration. Current project is based on previous project results, where the investigators of this project found signs of insulin resistance (IR) with hyperinsulinemia in patients with MS, which seem not to be related to chronic inflammation or low physical activity. Therefore aim of the present project is to elucidate impact of mitochondrial dysfunction in the pathogenesis of impaired insulin action and its role in the neurodegenerative process. To test the hypothesis, mitochondrial function, endothelial function, changes in membrane proteins and function of autonomic nervous system will be assessed. Those parameters will be measured non-invasively and in samples of blood, cerebrospinal fluid and skeletal muscle. MS patients will be examined at the time of diagnosis and after 12 months of treatment; healthy subjects will be used as controls. Elucidation of insulin resistance cause and the role of mitochondrial dysfunction in pathogenesis of disease is expected. Potential outcome of the project could be the answer, if pharmacological or non-pharmacological intervention might lead to improvement of mitochondrial function and therefore represent a new approach to prevent MS progression.
Interventions
DIAGNOSTIC_TESTOral glucose tolerance test
Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load
DIAGNOSTIC_TESTTesting of autonomous nervous system function
Autonomous nervous system function will be assessed using a battery of tests (orthostasis, Valsalva manoeuvre, heart rate variability recording, blood hormone levels, ect.)
DIAGNOSTIC_TESTStroop test
Stroop test will be used to test cognitive function
Sponsors
Comenius University
Slovak Academy of Sciences
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
for MS patients: * Age: 18-45 years * Recent diagnosis of MS based on McDonald criteria * Functional disability defined by the EDDS in the range of 2 to 6 * Patient demonstrates ability to successfully perform physical therapy exercises and procedures independently or with assistance of a caregiver
Exclusion criteria
* smoking, pregnancy, lactation, received a course of steroids (intravenous or oral) within 60 days of screening, diabetes, hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | 2017-2019 | Insulin sensitivity indices calculated from plasma glucose and insulin concentrations during oral glucose tolerance test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expanded Disability Status Scale (EDSS) | 2017-2020 | Expanded Disability Status Scale (EDSS) was developed for rating overall disability in MS. Patients are graded on the basis of presenting symptoms in eight different functional systems (FS), including pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, mental, and other functions. Scoring of the EDSS uses a 0 to 10, 20-step scale, with 0 equal to normal neurological function, 6.0 requires an assistive device for walking and 10.0 equal to death due to MS. The final score is based on grades obtained in the FS assessment. |
Countries
Slovakia
Outcome results
None listed