Multiple Sclerosis: The Role of Mitochondrial Dysfunction in IR Resistance

Completed

• Conditions: Multiple Sclerosis; Mitochondrial Alteration
• Interventions: Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Testing of autonomous nervous system function; Diagnostic Test: Stroop test

• Registration Number: NCT03052595
• Lead Sponsor: Slovak Academy of Sciences

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.

Study Timeline

• Study Start: 2017-02-01
• Study First Submitted: 2017-02-10
• Study First Submitted QC: 2017-02-13
• Study First Posted: 2017-02-14
• Primary Completion: 2023-03-31
• Study Completion: 2023-03-31
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-11
• Last Update Posted: 2023-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

• smoking, pregnancy, lactation, received a course of steroids (intravenous or oral) within 60 days of screening, diabetes, hypertension

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control	Stroop test	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)
SM	Stroop test	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)
Control	Oral glucose tolerance test	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)
SM	Oral glucose tolerance test	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)
SM	Testing of autonomous nervous system function	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)
Control	Testing of autonomous nervous system function	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)

Primary Outcome Measures

Name	Time	Method
Insulin sensitivity	2017-2019	Insulin sensitivity indices calculated from plasma glucose and insulin concentrations during oral glucose tolerance test

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Biomedical Center, Slovak Academy of Sciences, Institute of clinical and translational reasearch; 🇸🇰 Bratislava, Slovakia