Multiple Sclerosis: The Role of Mitochondrial Dysfunction in IR Resistance

NCT ID: NCT03052595

Last Updated: 2023-04-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

70 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-02-01

Study Completion Date

2023-03-31

Brief Summary

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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

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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.

Conditions

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Multiple Sclerosis Mitochondrial Alteration

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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)

Oral glucose tolerance test

Intervention Type DIAGNOSTIC_TEST

Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load

Testing of autonomous nervous system function

Intervention Type DIAGNOSTIC_TEST

Autonomous nervous system function will be assessed using a battery of tests (orthostasis, Valsalva manoeuvre, heart rate variability recording, blood hormone levels, ect.)

Stroop test

Intervention Type DIAGNOSTIC_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)

Oral glucose tolerance test

Intervention Type DIAGNOSTIC_TEST

Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load

Testing of autonomous nervous system function

Intervention Type DIAGNOSTIC_TEST

Autonomous nervous system function will be assessed using a battery of tests (orthostasis, Valsalva manoeuvre, heart rate variability recording, blood hormone levels, ect.)

Stroop test

Intervention Type DIAGNOSTIC_TEST

Stroop test will be used to test cognitive function

Interventions

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Oral glucose tolerance test

Oral glucose tolerance test to measure glucose and insulin concentrations after oral glucose load

Intervention Type 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.)

Intervention Type DIAGNOSTIC_TEST

Stroop test

Stroop test will be used to test cognitive function

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Comenius University

OTHER

Sponsor Role collaborator

Slovak Academy of Sciences

OTHER_GOV

Sponsor Role lead

Responsible Party

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Adela Penesova, MD, PhD

Responsible Clinical Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Viera Sevcikova, Ing

Role: STUDY_CHAIR

Biomedical Research Center of Slovak Academy of Sciences

Locations

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Biomedical Center, Slovak Academy of Sciences, Institute of clinical and translational reasearch

Bratislava, , Slovakia

Site Status

Countries

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Slovakia

References

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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.

Reference Type DERIVED
PMID: 33665745 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32178676 (View on PubMed)

Other Identifiers

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APVV 15-0228

Identifier Type: -

Identifier Source: org_study_id

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