Evaluation of Muscle Oxidative Capacity Relationship With Muscular Endurance, Fatigue (Multiple Sclerosis).

Multiple Sclerosis Clinical Trial

— OXYSEP  

Official title:

Non-invasive Evaluation of Muscle Oxidative Capacity. Study of Its Relationship With Muscular Endurance and Fatigue in Patients With Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06083194
• Other study ID #: RBHP 2023 COSTES
• Status: Recruiting
• Start date: January 14, 2024
• Est. completion date: June 2025

Study information

• Verified date: October 2023
• Source: University Hospital, Clermont-Ferrand
• Contact: Lise LACLAUTRE
• Phone: 334.73.754.963
• Email: promo_interne_drci[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. It is characterized by different progressive forms with periods of flare-ups interspersed with phases of remission. MS manifests clinically with signs of multiple neurological dysfunctions as well as less specific symptoms such as fatigue, the prevalence of which is found to be high in these patients and is independently associated with an alteration in their quality of life.

Recently, a non-invasive method for assessing maximal muscle oxidative capacity (mVO2) using optical measurement of muscle oxygenation (near-infrared spectroscopy, NIRS) has been described. Measuring tissue light absorption from a skin sensor facing a muscle, makes it possible to distinguish tissue concentrations of oxyhemoglobin (HbO2) and hemoglobin (Hb). The difference in absorbance of Hb and HbO2 corresponds to the balance of O2 supply and consumption in tissue capillaries, allowing calculation of a time constant (kNIRS, min-1) reflecting mitochondrial function.

Current literature provides reference values in young healthy subjects and MS patients. This index could therefore constitute a particularly interesting non-invasive indicator of mitochondrial functioning, usable in the clinic.

Description:

Following an arterial occlusion, the rate of decay of the NIRS signal is only dependent on local O2 consumption. Following an exercise increasing the oxygen consumption of the muscle (isometric contractions for 10 to 15 s), carrying out a series of brief occlusions makes it possible to calculate mVO2 (slope of O2 desaturation at each occlusion). mVO2 decreases exponentially with time, allowing calculation of a time constant (kNIRS, min-1) reflecting mitochondrial function. Furthermore, it has been shown that kNIRS correlates with mitochondrial respiration rate measured in oxygraphy (Ryan et al., 2014).

A few studies have focused on the link between maximal muscular oxidative capacity (mVO2), fatigue and muscular endurance in patients with MS. Furthermore, contradictory results have been reported regarding mVO2 in this population, suggesting in one case a higher mVO2 compared to healthy subjects while others observe the opposite. This results in an imprecise assessment of maximum muscle oxidative capacity (mVO2) in MS patients and its relationship with fatigue and muscular endurance in this population. The investigator therefore propose to carry out a prospective interventional study to analyze the relationship between these different parameters. The investigator's hypothesis is the existence of a positive correlation between mVO2 and muscular endurance, and negative with fatigue. This relationship will also be sought 6 months after participants engagement in regular physical activity. Given the accumulation of functional deficits, this approach is focused on preventive medicine, and with the aim of improving the care of these patients.

The statistical analyzes will be carried out with Stata software (version 15; StataCorp, College Station, Texas, USA), considering a risk of two-sided first type error of 5%.

Continuous variables will be presented in the form of mean and standard deviation, according to the normality of their distribution (Shapiro-Wilk test if necessary). In case of non-normality, they will be presented in the form of median, quartiles and extreme values. Qualitative variables will be expressed in numbers and associated percentages.

Graphical representations will, as much as possible, be associated with these analyses.

A description of the deviations from the protocol, the patients distributed according to these deviations and the causes of abandonment will also be carried out. The number of patients included and the inclusion curve will be presented by group.

Patients will be described at inclusion according to the following variables: compliance with eligibility criteria, epidemiological characteristics, clinical characteristics and possible treatments.

The main analysis aiming to investigate the association between maximum muscle oxidative capacity (mVO2) of MS patients assessed by near-infrared spectroscopy (NIRS) and muscular endurance of the gastrocnemius muscles assessed with the unipedal plantar flexion test (Single- Leg standing Heel Raise Test (SLSHR)) will be based on a regression coefficient (Pearson or Spearman with regard to the statistical distribution), interpreted with regard to the recommendations reported in the literature.

The main analysis could be supplemented by a multivariate analysis aimed at taking into account possible confounding factors (including form/type of MS, functional deficits and age); a multiple linear regression will be proposed. The normality of the residuals will be studied; if necessary, a transformation (for example logarithmic) of the dependent variable of the study may be proposed). The results will then be expressed in terms of regression coefficients and 95% confidence interval. A subgroup analysis of the main analysis will be carried out (if possible), according to age, MS, and functional deficits; which will make it possible to evaluate the robustness of the results with regard to the heterogeneity of the sample under study and the possible impact of these variables in addition to the aforementioned multivariate analysis. The maximum muscular oxidative capacity and the muscular endurance of the gastrocnemius muscles could, secondly, be treated and analyzed as categorical data with regard to the work reported in the literature; the study of their relationship will then be analyzed by the most appropriate statistical test. For the study of the relationship between two categorical variables, a chi2 test or a Fisher exact test will be confirmed by presenting the results in terms of absolute difference and 95% confidence interval. The secondary analyzes aiming to study the relationship between the maximum muscular oxidative capacity, the fatigue (FACIT-F questionnaire) and the walking capacity will be based on a regression coefficient (Pearson or Spearman with regard to the statistical distribution) and will be interpreted with regard to the recommendations reported in the literature. The variation in mVO2 at 6 months following the engagement in physical activity [assessed by the variation in energy expenditure (number of METs per week)] will be studied by the paired Student test or the Wilcoxon test; Results will be expressed in terms of effect size and 95% confidence interval.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients with Multiple Sclerosis (MS) with a diagnosis established by MRI.

• Patients with a Kurtzke Expanded Disability Status Scale (EDSS) score < 5.

• Body mass index (BMI) < 30 Kg/m².

• Thickness of subcutaneous adipose tissue at the calf = 20 mm.

• MS patients without neurological signs of flare-up since 1 month.

• MS patients who have not had any treatment modification during the last 2 months.

• Subjects affiliated to French health care system (for France).

• Volunteers who have given their written consent.

Exclusion Criteria:

• Patients suffering from progressive psychiatric pathologies (active psychosis, , etc.) or the presence of another serious unstabilized pathology (decompensated heart failure, progressive terminal cancer, etc.).

• People with poorly controlled or unstable cardiovascular disease.

• Major osteoarticular or neurological problems completely preventing the proper performance of the various tests.

• Persons under guardianship, curatorship, deprived of liberty or safeguarding justice.

• Pregnant or lactating women.

Related Conditions & MeSH terms

• Fatigue
• Multiple Sclerosis
• Sclerosis

Locations

Country	Name	City	State
France	CHU clermont-ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

References & Publications (28)

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal muscle oxidative capacity (mVO2)	Maximal muscle oxidative capacity will be measured by near-infrared spectroscopy (NIRS)	At the beginning of the protocol inclusion day (to) and at 6 months (t1)
Primary	Muscular endurance of the gastrocnemius muscles	Muscular endurance of the gastrocnemius muscles, represented by the number of repetitions measured with the Single-Leg Heel Raise Test.	At the beginning of the protocol inclusion day (to) and at 6 months (t1)
Secondary	Expanded Disability Status Scale (EDSS)	Medical information about the degree of disability patients with Multiple Sclerosis (MS) using the EDSS score; varying between (0 -10). Higher the value higher the disability.	At the beginning of the protocol inclusion day (to)
Secondary	Weight (Kg)	Weight will be measured with the medical body weight scale SECA® and according to the ISAK recommendations.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Height (cm)	Height will be measured with a wall mounted tape measure and according to the ISAK recommendations.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Waist circumference (cm)	Waist circumference will be measured with a medical body tape measure and according to the ISAK recommendations.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Hip circumference (cm)	Hip circumference will be measured with a medical body tape measure and according to the ISAK recommendations.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Body Mass Index (Kg/m²)	BMI will be calculated (weight in kilograms divided by height in meters squared).	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Body composition	Body composition (muscle and fat) will be measured using he Bodystat® Impedance-meter.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Thickness of subcutaneous adipose tissue of the gastrocnemius muscles (mm)	the measure will be performed using a portable ultrasound machine (Sonobook 6 (CHISON Medical Technologies Co., Ltd.) with a linear probe (40 MHz - 150MHz Linear L7-V). The patient will be in a standing position with the foot placed on a stool so that the thigh is parallel to the ground and the knee joint forms a 90° angle.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Functional capacity	Functional capacity will be evaluated using the 6-minute walk test.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Gastrocnemius muscle endurance (number of repetitions and time(sec))	Muscular endurance of the gastrocnemius muscles will be measured with theSingle-Leg Heel Raise Test. Number of repetition will be recorded as well as the time to failure.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Energy expenditure level (MET/minute/week)	Physical activity will be measured using the Global Physical Activity Questionnaire (GPAQ)	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Functional Assessment of Chronic Illness Therapy Fatigue Scale	The degree of fatigue will be evaluated with the FACIT-F Questionnaire. Score varying between 0 to 52. Higher the score higher the fatigue.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	VO2max (maximal oxygen consumption) (mL/Kg/min)	: VO2max will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Maximum power (Watts)	Maximum power will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Threshold power (Watts)	Threshold power will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Maximum heart rate (bpm)	Maximum heart rate will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Threshold heart rate (bpm)	Threshold heart will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Forced vital Capacity (L and % of the theoretical value)	Forced vital Capacity will be measured with a spirometry test	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Forced Expiratory volume (L and % of the theoretical value)	Forced Expiratory volume will be measured with a spirometry test	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Tiffeneau ratio (%)	Tiffeneau ratio will be calculated by dividing the Forced Expiratory volume to the Forced vital Capacity.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Ventilatory reserve (%)	Ventilatory reserve will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Secondary	Tissue saturation index (kNIRS, min-1)	For the determination of mVO2 The patient will be lying down, a cuff (Hokanson SC 12L) will be placed at the level of the thigh, 2 cm from the upper edge of the patella. The NIRS sensor (Portamon, Artinis, Netherlands) will be positioned opposite the body of the two gastrocnemius at the level of its maximum arch, maintained and protected from ambient light by an elastic bandage. The calculation of the absorbances at the 2 wavelengths will be carried out by specific software (Oxysoft) making it possible to display in real time the relative concentrations of Hb and HbO2 and the tissue oxygen saturation (TSI) reflecting muscle O2 saturation.	At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)