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

NCT03243812 | Completed

• 1 other identifier: 69HCL17_0313
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Muscle function; Hemorheological disorders

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Surface Electromyography (EMG) Activity

  Day 1

• Muscle oxygenation measurement

  Day 1

• Measurement of six-minute walk distance (6MWD)

  Day 1

• Complete Blood Count (CBC)

  Day 1

• Hematocrit

  Day 1

Study Arms (3)

SS genotype group

ACTIVE COMPARATOR

Sickle cell patients with SS genotype. Each subject will undergo the following : 1. Blood sample 2. Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test 3. Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery. 4. Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society

Biological: Blood sampling; Other: Maximum Voluntary Contraction (MVC) test force; Other: Localized muscle endurance test; Other: Self-paced six-minute walk test

SC genotype group

ACTIVE COMPARATOR

Sickle cell patients with SC genotype. Each subject will undergo the following : 1. Blood sample 2. Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test 3. Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery. 4. Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society

Biological: Blood sampling; Other: Maximum Voluntary Contraction (MVC) test force; Other: Localized muscle endurance test; Other: Self-paced six-minute walk test

control group

ACTIVE COMPARATOR

Healthy subjects. Each subject will undergo the following : 1. Blood sample 2. Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test 3. Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery. 4. Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society

Biological: Blood sampling; Other: Maximum Voluntary Contraction (MVC) test force; Other: Localized muscle endurance test; Other: Self-paced six-minute walk test

Interventions

Blood sampling BIOLOGICAL

Blood sampling will be performed to assess hematological and hemorheological parameters

SC genotype group; SS genotype group; control group

Maximum Voluntary Contraction (MVC) test force OTHER

Maximum Voluntary Contraction (MVC) test force will be performed before and after a localized muscle endurance test

SC genotype group; SS genotype group; control group

Localized muscle endurance test OTHER

Subject will perform 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.

SC genotype group; SS genotype group; control group

Self-paced six-minute walk test OTHER

Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society

SC genotype group; SS genotype group; control group

Eligibility Criteria

• Age: 15 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Edouard Herriot

Lyon, 69003, France

Location

Related Publications (1)

• Gouraud E, Connes P, Gauthier-Vasserot A, Faes C, Merazga S, Poutrel S, Renoux C, Boisson C, Joly P, Bertrand Y, Hot A, Cannas G, Hautier C. Is Skeletal Muscle Dysfunction a Limiting Factor of Exercise Functional Capacity in Patients with Sickle Cell Disease? J Clin Med. 2021 May 22;10(11):2250. doi: 10.3390/jcm10112250.

  PMID: 34067352 RESULT

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Giovanna CANNAS, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 9, 2017
• Study Start: September 15, 2017
• Primary Completion: December 13, 2019
• Study Completion: December 13, 2019
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)