Muscle Function and Its Biological and Physiological Determinants in Sickle Cell Disease

Hospices Civils de Lyon77 enrolled

Overview

Background : Sickle cell patients have profound remodeling of their muscle microcirculation networks with signs of amyotrophy. However, the consequences of these muscle alterations on the functional status of muscles are unknown. In addition, whether the poor physical fitness of sickle cell patients can be attributed, at least partly, to an hypothetical muscle dysfunction has never been tested. Purpose : this study will compare the muscle function of legs between sickle cell patients (SS and SC genotypes) and healthy individuals (AA genotype) before, during and after a short localized muscle endurance exercise. Abstract : Very recently, a study reported large differences between the muscle microcirculation networks of sickle cell patients compared to healthy individuals with decreased capillary density and higher proportion of large capillaries in the former population. In addition, the same study showed signs of amyotrophy in sickle cell patients. However, the muscle function of sickle cell patients has not been investigated and one may suggest that muscle dysfunction could participate in the decrease of physical fitness, in association with the hematological and hemorheological disorders, already reported in this population. The hypothesis is that muscle fatigue during a short localized muscle endurance exercise should be higher in sickle cell patients compared to healthy individuals, due to a greater recruitment of glycolytic fibers and a faster decrease of muscle oxygenation during exercise.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Sickle Cell Disease

Eligibility

Sex: ALLMin age: 15 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: For Sickle cell patients : * age ≥ 15 and \< 60 years old, * SS homozygote or SC heterozygote * in clinical steady state (i.e. without vaso-occlusive crisis or recent blood transfusion) * identified by systematic neonatal screening programs, * registered in the French medical social security national program For Healthy and non sickle cell subjects: * age ≥ 18 and \< 60 years old * without cardiovascular/respiratory/muscle disease, * registered in the French medical social security national program. Exclusion Criteria: * other hemoglobinopathies, * stroke or vasculopathy history, * presence of leg ulcers or osteonecrosis, * recent infectious episode (less than 1 month), * chronic transfusion therapy programs, * recent blood transfusion or phlebotomies (less than 3 months), * patients not at steady state, * pregnancy or breast feeding

Outcomes

Primary Outcomes

Maximum isometric muscular strength

Isometric muscular strength will be determined by Maximum Voluntary Contraction (MVC) test force on dominant leg. Muscular function will be evaluated using Maximum Voluntary Contraction (MVC) test force and the muscle endurance ability, which will be highlighted by the degree of decline of MVC after a short localized muscle effort using the formula: ((post MVC force - pre MVC force) / pre MVC force)x100. Muscle weakness will be determined by a loss of maximum isometric strength ≥ 20 % compared with control group.

Time frame: Day 1

Secondary Outcomes

Surface Electromyography (EMG) Activity

Surface EMG signals will be recorded by non-invasive electrodes on the dominant leg.

Time frame: Day 1

Muscle oxygenation measurement

oxyhemoglobin (HbO2) and deoxyhemoglobin (HHb) levels will be measured using Near-Infrared spectroscopy on the dominant leg.

Time frame: Day 1

Measurement of six-minute walk distance (6MWD)

In order to investigate the association between muscle endurance ability and physical fitness in sickle cell patients, patients will realize a six-minute walk test (6MWT). 6MWD will be measured = the distance that a patient has walked on a flat, hard surface in a period of 6 minutes (6MWT).

Time frame: Day 1

Complete Blood Count (CBC)

CBC will be performed in order to evaluate the role of hematological disorders in the muscle fatigue of sickle cell patients.

Time frame: Day 1

Hematocrit

Hematocrit will be measured in order to evaluate the role of hematological disorders in the muscle fatigue of sickle cell patients.

Time frame: Day 1

Blood viscosity

Blood viscosity will be measured by using viscosimetry, in order to evaluate the role of hemorheological disorders in the muscle fatigue of sickle cell patients.

Time frame: Day 1

Red blood cell (RBC) deformability

RBC deformability will be assessed by using ektacytometry, in order to evaluate the role of hemorheological disorders in the muscle fatigue of sickle cell patients.

Time frame: Day 1

Aggregation properties

Aggregation properties will be assessed by using syllectometry, in order to evaluate the role of hemorheological disorders in the muscle fatigue of sickle cell patients.

Time frame: Day 1

Hemoglobin oxygenation level

Hemoglobin oxygenation level will be measured in order to evaluate the role of hemorheological disorders in the muscle fatigue of sickle cell patients.

Time frame: Day 1

Number of vaso-occlusive crises and acute chest syndrome within a 5 years retrospective period.

Number of vaso-occlusive crises and acute chest syndrome reflects of clinical severity of the sickle cell disease. Clinical severity will be retrospectively (5 years) collected in clinical record of sickle cell patients. These clinical data will be used to study the relationships between the degree of muscle dysfunction and the degree of clinical severity in sickle cell patients.

Time frame: Day 1

Muscle Function and Its Biological and Physiological Determinants in Sickle Cell Disease

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes