Multiple Sclerosis: The Role of Mitochondrial Dysfunction in IR Resistance (MS-MIDY)

Multiple Sclerosis: The Role of Mitochondrial Dysfunction in Insulin Resistance

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Mitochondrial Alteration
• Intervention / Treatment: Diagnostic test: Oral glucose tolerance test; Diagnostic test: Testing of autonomous nervous system function; Diagnostic test: Stroop test

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.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Slovakia
  • Bratislava, Slovakia, 84505
    • Biomedical Center, Slovak Academy of Sciences, Institute of clinical and translational reasearch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SM; Patients with newly diagnosed multiple sclerosis undergo Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load Patients undergo testing of autonomous nervous system function and testing of cognitive function (Stroop test)	Diagnostic test: Oral glucose tolerance test; Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load; Diagnostic test: Testing 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 test: Stroop test; Stroop test will be used to test cognitive function
Control; Age, sex, Body Mass Index (BMI) matched healthy subjects undergo Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load Healthy controls undergo testing of autonomous nervous system function and testing of cognitive function (Stroop test)	Diagnostic test: Oral glucose tolerance test; Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load; Diagnostic test: Testing 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 test: Stroop test; Stroop test will be used to test cognitive function

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Insulin sensitivity indices calculated from plasma glucose and insulin concentrations during oral glucose tolerance test	2017-2019

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded Disability Status Scale (EDSS)	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.	2017-2020

Collaborators and Investigators

• Sponsor: Slovak Academy of Sciences
• Collaborators: Comenius University
• Investigators: Study Chair: Viera Sevcikova, Ing, Biomedical Research Center of Slovak Academy of Sciences

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: February 10, 2017
• First Submitted That Met QC Criteria: February 13, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: APVV 15-0228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No