An observational study in Multiple Sclerosis, sponsored by University Hospital, Clermont-Ferrand. Recruiting at 1 site in France. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-01-17.
Sponsored by University Hospital, Clermont-Ferrand · Observational
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.
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.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
This study's planned enrollment of 30 is below the median of 100 across 1,016 observational studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →University Hospital, Clermont-Ferrand is the lead sponsor of 841 studies on the registry; 178 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with Multiple Sclerosis with a Kurtzke Expanded Disability Status Scale (EDSS) score \< 5 prospectively assesed for muscle oxidative capacity and muscle endurance.
Exclusion Criteria:
Maximal muscle oxidative capacity (mVO2)
Maximal muscle oxidative capacity will be measured by near-infrared spectroscopy (NIRS)
Time frame: At the beginning of the protocol inclusion day (to) and at 6 months (t1)
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.
Time frame: At the beginning of the protocol inclusion day (to) and at 6 months (t1)
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.
Time frame: At the beginning of the protocol inclusion day (to)
Weight (Kg)
Weight will be measured with the medical body weight scale SECA® and according to the ISAK recommendations.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Height (cm)
Height will be measured with a wall mounted tape measure and according to the ISAK recommendations.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Waist circumference (cm)
Waist circumference will be measured with a medical body tape measure and according to the ISAK recommendations.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Hip circumference (cm)
Hip circumference will be measured with a medical body tape measure and according to the ISAK recommendations.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Body Mass Index (Kg/m²)
BMI will be calculated (weight in kilograms divided by height in meters squared).
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Body composition
Body composition (muscle and fat) will be measured using he Bodystat® Impedance-meter.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Functional capacity
Functional capacity will be evaluated using the 6-minute walk test.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Energy expenditure level (MET/minute/week)
Physical activity will be measured using the Global Physical Activity Questionnaire (GPAQ)
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Maximum power (Watts)
Maximum power will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Threshold power (Watts)
Threshold power will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Forced vital Capacity (L and % of the theoretical value)
Forced vital Capacity will be measured with a spirometry test
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Forced Expiratory volume (L and % of the theoretical value)
Forced Expiratory volume will be measured with a spirometry test
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Tiffeneau ratio (%)
Tiffeneau ratio will be calculated by dividing the Forced Expiratory volume to the Forced vital Capacity.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
Ventilatory reserve (%)
Ventilatory reserve will be obtained by performing a cardiopulmonary exercise testing at maximal effort during incremental exercise on a cycle ergometer.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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.
Time frame: At the beginning of the protocol inclusion day (to), at 6 months from the inclusion (t1)
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