Clinical trial NCT03052595: Multiple Sclerosis: The Role of Mitochondrial Dysfunction in IR Resistance
Official title: Multiple Sclerosis: The Role of Mitochondrial Dysfunction in Insulin Resistance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Mitochondrial Alteration
Lead sponsor: Slovak Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Comenius University
First posted: 2017-02-14
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with newly diagnosed MS will be examined twice: immediately after the diagnosis confirmation and after at least 12 months of MS treatment

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.

Eligibility criteria: 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

Primary outcomes:
measure: Insulin sensitivity
timeFrame: 2017-2019
Secondary outcomes:
measure: Expanded Disability Status Scale (EDSS)
timeFrame: 2017-2020
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: Biomedical Center, Slovak Academy of Sciences, Institute of clinical and translational reasearch
Study officials:
affiliation: Biomedical Research Center of Slovak Academy of Sciences
name: Viera Sevcikova, Ing
role: STUDY_CHAIR
References:
citation: Imrich R, Vlcek M, Penesova A, Radikova Z, Havranova A, Sivakova M, Siarnik P, Kollar B, Sokolov T, Turcani P, Heckova E, Hangel G, Strasser B, Bogner W. Cardiac autonomic function in patients with early multiple sclerosis. Clin Auton Res. 2021 Aug;31(4):553-562. doi: 10.1007/s10286-021-00790-w. Epub 2021 Mar 4.
citation: Radikova Z, Penesova A, Vlcek M, Havranova A, Sivakova M, Siarnik P, Zitnanova I, Imrich R, Turcani P, Kollar B. Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation? Lipids Health Dis. 2020 Mar 17;19(1):49. doi: 10.1186/s12944-020-01221-x.