Clinical trial NCT06083194: Evaluation of Muscle Oxidative Capacity Relationship With Muscular Endurance, Fatigue (Multiple Sclerosis).
Official title: Non-invasive Evaluation of Muscle Oxidative Capacity. Study of Its Relationship With Muscular Endurance and Fatigue in Patients With Multiple Sclerosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Near infrared spectroscopy (NIRS)
Physical capacities
Fatigue
Muscle oxidative capacity
Skeletal muscle mitochondrial capacity
Muscle oxygen consumption
Single-Leg Heel Raise Test
Endurance
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2023-10-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Multiple Sclerosis with a Kurtzke Expanded Disability Status Scale (EDSS) score \< 5 prospectively assesed for muscle oxidative capacity and muscle endurance.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximal muscle oxidative capacity (mVO2)
timeFrame: At the beginning of the protocol inclusion day (to) and at 6 months (t1)
measure: Muscular endurance of the gastrocnemius muscles
timeFrame: At the beginning of the protocol inclusion day (to) and at 6 months (t1)
Secondary outcomes:
measure: Expanded Disability Status Scale (EDSS)
timeFrame: At the beginning of the protocol inclusion day (to)
measure: Weight (Kg)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Height (cm)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Waist circumference (cm)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Hip circumference (cm)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Body Mass Index (Kg/m²)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Body composition
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Thickness of subcutaneous adipose tissue of the gastrocnemius muscles (mm)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Functional capacity
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Gastrocnemius muscle endurance (number of repetitions and time(sec))
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Energy expenditure level (MET/minute/week)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Functional Assessment of Chronic Illness Therapy Fatigue Scale
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: VO2max (maximal oxygen consumption) (mL/Kg/min)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Maximum power (Watts)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Threshold power (Watts)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Maximum heart rate (bpm)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Threshold heart rate (bpm)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Forced vital Capacity (L and % of the theoretical value)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Forced Expiratory volume (L and % of the theoretical value)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Tiffeneau ratio (%)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Ventilatory reserve (%)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
measure: Tissue saturation index (kNIRS, min-1)
timeFrame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU clermont-ferrand
Study officials:
affiliation: fcostes@chu-clermontferrand.fr
name: Fréderic COSTES
role: PRINCIPAL_INVESTIGATOR
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