Muscle Function and Its Biological and Physiological Determinants in Sickle Cell Disease (DREPAMUSCLE)

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 Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Biological: Blood sampling; Other: Maximum Voluntary Contraction (MVC) test force; Other: Localized muscle endurance test; Other: Self-paced six-minute walk test

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69003
    • Hôpital Edouard Herriot

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 60 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: SS genotype group; Sickle cell patients with SS genotype. Each subject will undergo the following : Blood sample; Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test; Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.; Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society	Biological: Blood sampling; Blood sampling will be performed to assess hematological and hemorheological parameters; Other: Maximum Voluntary Contraction (MVC) test force; Maximum Voluntary Contraction (MVC) test force will be performed before and after a localized muscle endurance test; Other: Localized muscle endurance test; Subject will perform 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.; Other: Self-paced six-minute walk test; Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society
ACTIVE_COMPARATOR: SC genotype group; Sickle cell patients with SC genotype. Each subject will undergo the following : Blood sample; Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test; Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.; Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society	Biological: Blood sampling; Blood sampling will be performed to assess hematological and hemorheological parameters; Other: Maximum Voluntary Contraction (MVC) test force; Maximum Voluntary Contraction (MVC) test force will be performed before and after a localized muscle endurance test; Other: Localized muscle endurance test; Subject will perform 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.; Other: Self-paced six-minute walk test; Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society
ACTIVE_COMPARATOR: control group; Healthy subjects. Each subject will undergo the following : Blood sample; Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test; Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.; Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society	Biological: Blood sampling; Blood sampling will be performed to assess hematological and hemorheological parameters; Other: Maximum Voluntary Contraction (MVC) test force; Maximum Voluntary Contraction (MVC) test force will be performed before and after a localized muscle endurance test; Other: Localized muscle endurance test; Subject will perform 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.; Other: Self-paced six-minute walk test; Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surface Electromyography (EMG) Activity	Surface EMG signals will be recorded by non-invasive electrodes on the dominant leg.	Day 1
Muscle oxygenation measurement	oxyhemoglobin (HbO2) and deoxyhemoglobin (HHb) levels will be measured using Near-Infrared spectroscopy on the dominant leg.	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).	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.	Day 1
Hematocrit	Hematocrit will be measured in order to evaluate the role of hematological disorders in the muscle fatigue of sickle cell patients.	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.	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.	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.	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.	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.	Day 1

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Giovanna CANNAS, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2017
• Primary Completion (ACTUAL): December 13, 2019
• Study Completion (ACTUAL): December 13, 2019

Study Registration Dates

• First Submitted: July 27, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (ACTUAL): August 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Sickle Cell Disease; Muscle function; Hemorheological disorders
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: 69HCL17_0313

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No