<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03243812</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL17_0313</org_study_id>
    <nct_id>NCT03243812</nct_id>
  </id_info>
  <brief_title>Muscle Function and Its Biological and Physiological Determinants in Sickle Cell Disease</brief_title>
  <acronym>DREPAMUSCLE</acronym>
  <official_title>Muscle Function and Its Biological and Physiological Determinants in Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background : Sickle cell patients have profound remodeling of their muscle microcirculation&#xD;
      networks with signs of amyotrophy. However, the consequences of these muscle alterations on&#xD;
      the functional status of muscles are unknown. In addition, whether the poor physical fitness&#xD;
      of sickle cell patients can be attributed, at least partly, to an hypothetical muscle&#xD;
      dysfunction has never been tested.&#xD;
&#xD;
      Purpose : this study will compare the muscle function of legs between sickle cell patients&#xD;
      (SS and SC genotypes) and healthy individuals (AA genotype) before, during and after a short&#xD;
      localized muscle endurance exercise.&#xD;
&#xD;
      Abstract : Very recently, a study reported large differences between the muscle&#xD;
      microcirculation networks of sickle cell patients compared to healthy individuals with&#xD;
      decreased capillary density and higher proportion of large capillaries in the former&#xD;
      population. In addition, the same study showed signs of amyotrophy in sickle cell patients.&#xD;
      However, the muscle function of sickle cell patients has not been investigated and one may&#xD;
      suggest that muscle dysfunction could participate in the decrease of physical fitness, in&#xD;
      association with the hematological and hemorheological disorders, already reported in this&#xD;
      population. The hypothesis is that muscle fatigue during a short localized muscle endurance&#xD;
      exercise should be higher in sickle cell patients compared to healthy individuals, due to a&#xD;
      greater recruitment of glycolytic fibers and a faster decrease of muscle oxygenation during&#xD;
      exercise.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">December 13, 2019</completion_date>
  <primary_completion_date type="Actual">December 13, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum isometric muscular strength</measure>
    <time_frame>Day 1</time_frame>
    <description>Isometric muscular strength will be determined by Maximum Voluntary Contraction (MVC) test force on dominant leg.&#xD;
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.&#xD;
Muscle weakness will be determined by a loss of maximum isometric strength ≥ 20 % compared with control group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Surface Electromyography (EMG) Activity</measure>
    <time_frame>Day 1</time_frame>
    <description>Surface EMG signals will be recorded by non-invasive electrodes on the dominant leg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle oxygenation measurement</measure>
    <time_frame>Day 1</time_frame>
    <description>oxyhemoglobin (HbO2) and deoxyhemoglobin (HHb) levels will be measured using Near-Infrared spectroscopy on the dominant leg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of six-minute walk distance (6MWD)</measure>
    <time_frame>Day 1</time_frame>
    <description>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).&#xD;
6MWD will be measured = the distance that a patient has walked on a flat, hard surface in a period of 6 minutes (6MWT).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Blood Count (CBC)</measure>
    <time_frame>Day 1</time_frame>
    <description>CBC will be performed in order to evaluate the role of hematological disorders in the muscle fatigue of sickle cell patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematocrit</measure>
    <time_frame>Day 1</time_frame>
    <description>Hematocrit will be measured in order to evaluate the role of hematological disorders in the muscle fatigue of sickle cell patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood viscosity</measure>
    <time_frame>Day 1</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Red blood cell (RBC) deformability</measure>
    <time_frame>Day 1</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aggregation properties</measure>
    <time_frame>Day 1</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin oxygenation level</measure>
    <time_frame>Day 1</time_frame>
    <description>Hemoglobin oxygenation level will be measured in order to evaluate the role of hemorheological disorders in the muscle fatigue of sickle cell patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of vaso-occlusive crises and acute chest syndrome within a 5 years retrospective period.</measure>
    <time_frame>Day 1</time_frame>
    <description>Number of vaso-occlusive crises and acute chest syndrome reflects of clinical severity of the sickle cell disease.&#xD;
Clinical severity will be retrospectively (5 years) collected in clinical record of sickle cell patients.&#xD;
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.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">77</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>SS genotype group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sickle cell patients with SS genotype. Each subject will undergo the following :&#xD;
Blood sample&#xD;
Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test&#xD;
Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.&#xD;
Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SC genotype group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sickle cell patients with SC genotype. Each subject will undergo the following :&#xD;
Blood sample&#xD;
Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test&#xD;
Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.&#xD;
Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects. Each subject will undergo the following :&#xD;
Blood sample&#xD;
Maximum Voluntary Contraction (MVC) test force before and after a localized muscle endurance test&#xD;
Localized muscle endurance test: 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.&#xD;
Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>Blood sampling will be performed to assess hematological and hemorheological parameters</description>
    <arm_group_label>SC genotype group</arm_group_label>
    <arm_group_label>SS genotype group</arm_group_label>
    <arm_group_label>control group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Maximum Voluntary Contraction (MVC) test force</intervention_name>
    <description>Maximum Voluntary Contraction (MVC) test force will be performed before and after a localized muscle endurance test</description>
    <arm_group_label>SC genotype group</arm_group_label>
    <arm_group_label>SS genotype group</arm_group_label>
    <arm_group_label>control group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Localized muscle endurance test</intervention_name>
    <description>Subject will perform 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.</description>
    <arm_group_label>SC genotype group</arm_group_label>
    <arm_group_label>SS genotype group</arm_group_label>
    <arm_group_label>control group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Self-paced six-minute walk test</intervention_name>
    <description>Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society</description>
    <arm_group_label>SC genotype group</arm_group_label>
    <arm_group_label>SS genotype group</arm_group_label>
    <arm_group_label>control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For Sickle cell patients :&#xD;
&#xD;
          -  age ≥ 15 and &lt; 60 years old,&#xD;
&#xD;
          -  SS homozygote or SC heterozygote&#xD;
&#xD;
          -  in clinical steady state (i.e. without vaso-occlusive crisis or recent blood&#xD;
             transfusion)&#xD;
&#xD;
          -  identified by systematic neonatal screening programs,&#xD;
&#xD;
          -  registered in the French medical social security national program&#xD;
&#xD;
        For Healthy and non sickle cell subjects:&#xD;
&#xD;
          -  age ≥ 18 and &lt; 60 years old&#xD;
&#xD;
          -  without cardiovascular/respiratory/muscle disease,&#xD;
&#xD;
          -  registered in the French medical social security national program.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  other hemoglobinopathies,&#xD;
&#xD;
          -  stroke or vasculopathy history,&#xD;
&#xD;
          -  presence of leg ulcers or osteonecrosis,&#xD;
&#xD;
          -  recent infectious episode (less than 1 month),&#xD;
&#xD;
          -  chronic transfusion therapy programs,&#xD;
&#xD;
          -  recent blood transfusion or phlebotomies (less than 3 months),&#xD;
&#xD;
          -  patients not at steady state,&#xD;
&#xD;
          -  pregnancy or breast feeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giovanna CANNAS, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospices Civils de Lyon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>January 28, 2020</last_update_submitted>
  <last_update_submitted_qc>January 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>Muscle function</keyword>
  <keyword>Hemorheological disorders</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03243812
org study id: 69HCL17_0313
nct id: NCT03243812
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Maximum isometric muscular strength
time frame: Day 1
description: 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.
measure: Surface Electromyography (EMG) Activity
time frame: Day 1
description: Surface EMG signals will be recorded by non-invasive electrodes on the dominant leg.
measure: Muscle oxygenation measurement
time frame: Day 1
description: oxyhemoglobin (HbO2) and deoxyhemoglobin (HHb) levels will be measured using Near-Infrared spectroscopy on the dominant leg.
measure: Measurement of six-minute walk distance (6MWD)
time frame: Day 1
description: 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).
measure: Complete Blood Count (CBC)
time frame: Day 1
description: CBC will be performed in order to evaluate the role of hematological disorders in the muscle fatigue of sickle cell patients.
measure: Hematocrit
time frame: Day 1
description: Hematocrit will be measured in order to evaluate the role of hematological disorders in the muscle fatigue of sickle cell patients.
measure: Blood viscosity
time frame: Day 1
description: 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.
measure: Red blood cell (RBC) deformability
time frame: Day 1
description: 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.
measure: Aggregation properties
time frame: Day 1
description: 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.
measure: Hemoglobin oxygenation level
time frame: Day 1
description: Hemoglobin oxygenation level will be measured in order to evaluate the role of hemorheological disorders in the muscle fatigue of sickle cell patients.
measure: Number of vaso-occlusive crises and acute chest syndrome within a 5 years retrospective period.
time frame: Day 1
description: 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.
arm group label: SS genotype group
arm group type: Active Comparator
description: 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
arm group label: SC genotype group
arm group type: Active Comparator
description: 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
arm group label: control group
arm group type: Active Comparator
description: 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
intervention type: Biological
intervention name: Blood sampling
description: Blood sampling will be performed to assess hematological and hemorheological parameters
arm group label: SC genotype group
arm group label: SS genotype group
arm group label: control group
intervention type: Other
intervention name: Maximum Voluntary Contraction (MVC) test force
description: Maximum Voluntary Contraction (MVC) test force will be performed before and after a localized muscle endurance test
arm group label: SC genotype group
arm group label: SS genotype group
arm group label: control group
intervention type: Other
intervention name: Localized muscle endurance test
description: Subject will perform 4 series of 20 submaximal dynamic contractions at 50% of the MVC interspaced with 1 min recovery.
arm group label: SC genotype group
arm group label: SS genotype group
arm group label: control group
intervention type: Other
intervention name: Self-paced six-minute walk test
description: Self-paced six-minute walk test will be conducted according to the guidelines of the American Thoracic Society
arm group label: SC genotype group
arm group label: SS genotype group
arm group label: control group
criteria: 
gender: All
minimum age: 15 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Giovanna CANNAS, MD
role: Principal Investigator
affiliation: Hospices Civils de Lyon
facility: 
country: France
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
sharing ipd: No