<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/NCT03802279</url>
  </required_header>
  <id_info>
    <org_study_id>APHP 180 009</org_study_id>
    <secondary_id>2018-A01771-54</secondary_id>
    <nct_id>NCT03802279</nct_id>
  </id_info>
  <brief_title>Evaluate the Effort Test as a Therapeutic Monitoring Tool in Acute Rhabdomyolyses</brief_title>
  <acronym>EFFORHAB</acronym>
  <official_title>Study of the Correlation Between the Effort Test, With the Assessment of Peripheral Oxygen Consumption and Cardiac Output in Patients With Acute Rhabdomyolysis Related to a Hereditary Disease of Metabolism, and the Biochemical Flux on Myoblasts: Evaluate the Effort Test as a Therapeutic Monitoring Tool in Acute Rhabdomyolyses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and&#xD;
      treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by&#xD;
      fever and fasting. They are unpredictable. In spite of the care of patient in an intensive&#xD;
      care unit, the occurrence of renal failure and heart rhythm disorders explains a significant&#xD;
      acute-phase mortality rate. There is an urgent need to understand the pathophysiological&#xD;
      mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to&#xD;
      identify specific treatments.&#xD;
&#xD;
      Patients with rhabdomyolyses have few clinical signs outside of access. So there is a&#xD;
      methodological difficulty in following a treatment test. There is an urgency to identify&#xD;
      follow-up parameters in anticipation of new therapies.&#xD;
&#xD;
      The objective of this study is to validate the hypothesis that effort test and cardiac&#xD;
      function parameters are usable in the treatment monitoring for patients with acute&#xD;
      rhabdomyolysis linked to a hereditary disease of metabolism and thus propose the effort test&#xD;
      as an assessment tool for future clinical trials. In order to do so, the correlation between&#xD;
      the results of the effort tests, performed to each patient with rhabdomyolysis related to a&#xD;
      hereditary disease of metabolism, with the severity of the disease will be evaluated. This&#xD;
      study is original because it opens up innovative prospects for monitoring in the field of&#xD;
      hereditary diseases of metabolism, with the identification of new monitoring tools.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rhabdomyolysis is a poorly known symptom associated with the destruction of skeletal muscle&#xD;
      cells. The diagnosis of rhabdomyolyses is carried when the dosage of muscle enzymes, in&#xD;
      particular creatine phosphate kinase (KPC), is greater than 1000 U/L (normal &lt; 160 U/L).&#xD;
&#xD;
      Rhabdomyolyses may be of viral origin, but fever and viruses are also triggers of genetic&#xD;
      diseases. Also, the incidence of genetic rhabdomyolyses, representing 10 to 15% of all&#xD;
      rhabdomyolyses, is underestimated. Genetic causes are heterogeneous. They are mainly&#xD;
      attributed to hereditary diseases of metabolism, in particular fatty acid oxidation defects,&#xD;
      Lipin-1 deficiency, muscle glycogenoses, TANGO2 deficiency, mitochondrial cytopathies and&#xD;
      calcium channels anomalies of in particular RYR1.&#xD;
&#xD;
      Whatever the cause, traumatic, infectious or genetic, the rhabdomyolyses cause an alteration&#xD;
      of the metabolism of adenosine triphosphate and a deregulation of the ionic channels, with&#xD;
      the consequences of an intracytoplasmic calcium release and the destruction of muscle cells.&#xD;
&#xD;
      The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and&#xD;
      treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by&#xD;
      fever and fasting. They are unpredictable. In spite of the care of patient in an intensive&#xD;
      care unit, the occurrence of renal failure and heart rhythm disorders explains a significant&#xD;
      acute-phase mortality rate. There is an urgent need to understand the pathophysiological&#xD;
      mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to&#xD;
      identify specific treatments.&#xD;
&#xD;
      The pathophysiological mechanism of rhabdomyolyses related to Lipin-1 deficiency has been&#xD;
      identified. Two patients with Lipin-1 deficiency treated in vivo by Hydroxychloroquine&#xD;
      (Plaquenil ®, 6 mg/kg/day by one oral intake) rapidly standardized their serum inflammatory&#xD;
      profile and corrected their clinical phenotype: Plasma creatine phosphokinase levels, Amount&#xD;
      of mitochondrial DNA in plasma, number of myolyses, muscular pain, quality of life. One of&#xD;
      these two patients, suffering from cardiac dysfunction already reported in Lipin-1 deficiency&#xD;
      (left ventricular ejection fraction or LVEF 45%), significantly and durably improved cardiac&#xD;
      function after one month of treatment (LVEF 62%). In addition, his fatigability and sleep&#xD;
      disturbances have dramatically improved.&#xD;
&#xD;
      Disruption of mitophagy and immunity could be a common denominator for rhabdomyolyses linked&#xD;
      to hereditary diseases of metabolism, which could, despite their heterogeneity, benefit from&#xD;
      a common therapeutic approach, Now non-existent. There could be a role of inflammation in&#xD;
      rhabdomyolyses outbreaks of metabolic origin and new therapeutic approaches could be imagined&#xD;
      as in the Lipin-1 deficiency.&#xD;
&#xD;
      Patients with rhabdomyolyses have few clinical signs outside of access. So there is a&#xD;
      methodological difficulty in following a treatment test. There is an urgency to identify&#xD;
      follow-up parameters in anticipation of new therapies.&#xD;
&#xD;
      In the Lipin deficiency, an anomaly of the effort tests with measurement of oxygen&#xD;
      consumption and cardiac output was characterized. These effort tests were carried out in the&#xD;
      context of care, in order to recognize for a given patient whether the practice of sport is a&#xD;
      factor triggering rhabdomyolysis.&#xD;
&#xD;
      The objective of this study is to validate the hypothesis that effort test and cardiac&#xD;
      function parameters are usable in the treatment monitoring for patients with acute&#xD;
      rhabdomyolysis linked to a hereditary disease of metabolism and thus propose the effort test&#xD;
      as an assessment tool for future clinical trials. To date, no tests are available for&#xD;
      clinical trials. In order to do so, the correlation between the results of the effort tests,&#xD;
      performed to each patient with rhabdomyolysis related to a hereditary disease of metabolism,&#xD;
      with the severity of the disease will be assessed, including:&#xD;
&#xD;
      1) Metabolic flux on myoblasts, 2) clinical severity (onset of disease, number of&#xD;
      rhabdomyolyses, cardiomyopathy), 3) genotype.&#xD;
&#xD;
      This study is original because it opens up innovative prospects for monitoring in the field&#xD;
      of hereditary diseases of metabolism, with the identification of new monitoring tools.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 25, 2019</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of cardiac output (Q)</measure>
    <time_frame>Day 0</time_frame>
    <description>Effort test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of oxygen consumption (VO2)</measure>
    <time_frame>Day 0</time_frame>
    <description>Effort test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Calculation of the slope of the relationship heart rate-oxygen consumed (dQ/dVO2)</measure>
    <time_frame>Day 0</time_frame>
    <description>Effort test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Calculation of the maximum arteriovenous difference (DAV) : DAV=VO2/Q</measure>
    <time_frame>Day 0</time_frame>
    <description>Effort test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Calculation of maximum muscle diffusion (DM) using the equation of Fick: DM = (Q x DAV)/(200-DAV)</measure>
    <time_frame>Day 0</time_frame>
    <description>Effort test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peripheral muscular oxygenation</measure>
    <time_frame>Day 0</time_frame>
    <description>Measurement of peripheral muscular oxygenation during the effort test.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systolic ejection volume at the peak of the effort during the effort test</measure>
    <time_frame>Day 0</time_frame>
    <description>Evaluation of cardiac performance by the value of the systolic ejection volume at the peak of the effort.&#xD;
The systolic ejection volume is measured beat per beat during the effort test.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ejection fraction of the left ventricle</measure>
    <time_frame>Day 0</time_frame>
    <description>Measurement of the ejection fraction of the left ventricle in Simpson biplane and the longitudinal strain of the left ventricle in echocardiography.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolic pathways of myoblasts</measure>
    <time_frame>From study start until 26 months</time_frame>
    <description>Myoblasts will be incubated in the presence of stable isotope-labeled tracers. The natural metabolites labelled with stable isotopes will be dosed. The acylcarnitines will be dosed on a mass spectrometer. The Krebs cycle intermediates will be measured in gas chromatography coupled with mass spectrometry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Presence of cardiomyopathy</measure>
    <time_frame>Day 0</time_frame>
    <description>Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Age of onset of disease (neonatal, &lt; 2 years, 2 - 10 years, &gt; 10 years)</measure>
    <time_frame>Day 0</time_frame>
    <description>Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of acute episodes of rhabdomyolyses</measure>
    <time_frame>Day 0</time_frame>
    <description>Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Character of mutations nonsense or missense of the hereditary disease of metabolism</measure>
    <time_frame>Day 0</time_frame>
    <description>Genotypic severity of rhabdomyolysis linked to a hereditary disease of metabolism.&#xD;
Information available in the patient medical record.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">27</enrollment>
  <condition>Rhabdomyolysis Linked to a Hereditary Disease of Metabolism</condition>
  <arm_group>
    <arm_group_label>Rhabdomyolysis with myoblasts back up</arm_group_label>
    <description>Patients with a rhabdomyolysis linked to a hereditary disease of metabolism who have benefited from a diagnostically muscle biopsy and whose myoblasts are available.&#xD;
Patients benefit from an effort test as part of their care.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rhabdomyolysis</arm_group_label>
    <description>Patients with a rhabdomyolysis linked to a hereditary disease of metabolism who have benefited or not from a diagnostically muscle biopsy but whose myoblasts are not available.&#xD;
Patients benefit from an effort test as part of their care.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Witness patients : effort test</arm_group_label>
    <description>10 patient-matched healthy controls for age and sex having performed an effort test and cardiac exploration as part of their care.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Witness patients : myoblasts</arm_group_label>
    <description>6 healthy controls matched by age and sex having performed a muscle biopsy as part of their care and whose myoblasts are kept.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Effort test</intervention_name>
    <description>Cardiac function:&#xD;
Echocardiography: left ventricular ejection fraction and global longitudinal strain will be measured.&#xD;
Cardiopulmonary exercise test (CPET): left ventricular stroke volume was assessed noninvasively using a thoracic bioelectrical impedance device : maximal stroke volume at the peak of effort will be considered.&#xD;
Peripheral muscle function:&#xD;
CPET: Oxygen uptake (VO2) (and carbon dioxide) output are measured. The slope of the relationship (dQ/dVO2) will be calculated between cardiac output (Q) and VO2 using measurements of Q (using measure of the stroke volume by thoracic bioelectrical impedance device) and VO2 at rest as well as during submaximal and maximal exercise&#xD;
Muscle oxygenation is measured using a near-infrared spectroscopy device.&#xD;
VO2 et Q will be measured : dQ/dVO2 is high in case of oxydation defect; If Q is low because of a concommittant cardiac impairement, the DAV = VO2/Q, and DO = (Q x DAV) / (200 - DAV) will be calculated.</description>
    <arm_group_label>Rhabdomyolysis</arm_group_label>
    <arm_group_label>Rhabdomyolysis with myoblasts back up</arm_group_label>
    <arm_group_label>Witness patients : effort test</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Functional tests on fibroblasts</intervention_name>
    <description>Functional tests performed on fibroblasts in primary culture, using as tracers of stable isotope-labeled substrates. The metabolites of interest are assayed in mass spectrometry.</description>
    <arm_group_label>Rhabdomyolysis with myoblasts back up</arm_group_label>
    <arm_group_label>Witness patients : myoblasts</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The population to be studied consists of 40 patients with metabolic rhabdomyolyses followed&#xD;
        by the centre of reference for metabolic diseases of the child and adult of the Necker&#xD;
        Hospital.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        subjects with metabolic rhabdomyolysis related to a hereditary metabolic disease :&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  pathology characterized on the biochemical and molecular level&#xD;
&#xD;
          -  patients who can make an effort test&#xD;
&#xD;
          -  patients who benefited from a diagnostically targeted muscle biopsy with backup of&#xD;
             myoblasts (group 1)&#xD;
&#xD;
          -  patients who have benefited from a diagnostically targeted muscle biopsy but whose&#xD;
             myoblasts are not available (group 2) Exclusion Criteria&#xD;
&#xD;
          -  inability or refusal of compliance to the requirements of the research&#xD;
&#xD;
          -  patients with contraindications for the effort test in particular heart failure and&#xD;
             acute rhabdomyolysis&#xD;
&#xD;
          -  Patients without biochemical and/or molecular diagnosis&#xD;
&#xD;
        Criteria for inclusion of witness patients :&#xD;
&#xD;
          -  holders of parental authority and/or patients not opposed to the use of their&#xD;
             cardio-respiratory analysis results for this study or to the use of their myoblasts&#xD;
             for this study&#xD;
&#xD;
          -  normal cardio-respiratory analysis results&#xD;
&#xD;
          -  normal myoblasts (group 4).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pascale de Lonlay</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antoine Legendre, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Florence Habarou, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Caroline Tuchmann-Durand, Pharm. D, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Necker-Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rhabdomyolysis linked to a hereditary disease of metabolism</keyword>
  <keyword>Correlation between the effort test and the severity of the disease and biochemical flux on myoblasts</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhabdomyolysis</mesh_term>
    <mesh_term>Genetic Diseases, Inborn</mesh_term>
  </condition_browse>
  <!-- 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/NCT03802279
org study id: APHP 180 009
secondary id: 2018-A01771-54
nct id: NCT03802279
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and
      treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by
      fever and fasting. They are unpredictable. In spite of the care of patient in an intensive
      care unit, the occurrence of renal failure and heart rhythm disorders explains a significant
      acute-phase mortality rate. There is an urgent need to understand the pathophysiological
      mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to
      identify specific treatments.

      Patients with rhabdomyolyses have few clinical signs outside of access. So there is a
      methodological difficulty in following a treatment test. There is an urgency to identify
      follow-up parameters in anticipation of new therapies.

      The objective of this study is to validate the hypothesis that effort test and cardiac
      function parameters are usable in the treatment monitoring for patients with acute
      rhabdomyolysis linked to a hereditary disease of metabolism and thus propose the effort test
      as an assessment tool for future clinical trials. In order to do so, the correlation between
      the results of the effort tests, performed to each patient with rhabdomyolysis related to a
      hereditary disease of metabolism, with the severity of the disease will be evaluated. This
      study is original because it opens up innovative prospects for monitoring in the field of
      hereditary diseases of metabolism, with the identification of new monitoring tools.
Rhabdomyolysis is a poorly known symptom associated with the destruction of skeletal muscle
      cells. The diagnosis of rhabdomyolyses is carried when the dosage of muscle enzymes, in
      particular creatine phosphate kinase (KPC), is greater than 1000 U/L (normal < 160 U/L).

      Rhabdomyolyses may be of viral origin, but fever and viruses are also triggers of genetic
      diseases. Also, the incidence of genetic rhabdomyolyses, representing 10 to 15% of all
      rhabdomyolyses, is underestimated. Genetic causes are heterogeneous. They are mainly
      attributed to hereditary diseases of metabolism, in particular fatty acid oxidation defects,
      Lipin-1 deficiency, muscle glycogenoses, TANGO2 deficiency, mitochondrial cytopathies and
      calcium channels anomalies of in particular RYR1.

      Whatever the cause, traumatic, infectious or genetic, the rhabdomyolyses cause an alteration
      of the metabolism of adenosine triphosphate and a deregulation of the ionic channels, with
      the consequences of an intracytoplasmic calcium release and the destruction of muscle cells.

      The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and
      treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by
      fever and fasting. They are unpredictable. In spite of the care of patient in an intensive
      care unit, the occurrence of renal failure and heart rhythm disorders explains a significant
      acute-phase mortality rate. There is an urgent need to understand the pathophysiological
      mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to
      identify specific treatments.

      The pathophysiological mechanism of rhabdomyolyses related to Lipin-1 deficiency has been
      identified. Two patients with Lipin-1 deficiency treated in vivo by Hydroxychloroquine
      (Plaquenil ®, 6 mg/kg/day by one oral intake) rapidly standardized their serum inflammatory
      profile and corrected their clinical phenotype: Plasma creatine phosphokinase levels, Amount
      of mitochondrial DNA in plasma, number of myolyses, muscular pain, quality of life. One of
      these two patients, suffering from cardiac dysfunction already reported in Lipin-1 deficiency
      (left ventricular ejection fraction or LVEF 45%), significantly and durably improved cardiac
      function after one month of treatment (LVEF 62%). In addition, his fatigability and sleep
      disturbances have dramatically improved.

      Disruption of mitophagy and immunity could be a common denominator for rhabdomyolyses linked
      to hereditary diseases of metabolism, which could, despite their heterogeneity, benefit from
      a common therapeutic approach, Now non-existent. There could be a role of inflammation in
      rhabdomyolyses outbreaks of metabolic origin and new therapeutic approaches could be imagined
      as in the Lipin-1 deficiency.

      Patients with rhabdomyolyses have few clinical signs outside of access. So there is a
      methodological difficulty in following a treatment test. There is an urgency to identify
      follow-up parameters in anticipation of new therapies.

      In the Lipin deficiency, an anomaly of the effort tests with measurement of oxygen
      consumption and cardiac output was characterized. These effort tests were carried out in the
      context of care, in order to recognize for a given patient whether the practice of sport is a
      factor triggering rhabdomyolysis.

      The objective of this study is to validate the hypothesis that effort test and cardiac
      function parameters are usable in the treatment monitoring for patients with acute
      rhabdomyolysis linked to a hereditary disease of metabolism and thus propose the effort test
      as an assessment tool for future clinical trials. To date, no tests are available for
      clinical trials. In order to do so, the correlation between the results of the effort tests,
      performed to each patient with rhabdomyolysis related to a hereditary disease of metabolism,
      with the severity of the disease will be assessed, including:

      1) Metabolic flux on myoblasts, 2) clinical severity (onset of disease, number of
      rhabdomyolyses, cardiomyopathy), 3) genotype.

      This study is original because it opens up innovative prospects for monitoring in the field
      of hereditary diseases of metabolism, with the identification of new monitoring tools.
observational model: Case-Control
time perspective: Prospective
measure: Measurement of cardiac output (Q)
time frame: Day 0
description: Effort test
measure: Measurement of oxygen consumption (VO2)
time frame: Day 0
description: Effort test
measure: Calculation of the slope of the relationship heart rate-oxygen consumed (dQ/dVO2)
time frame: Day 0
description: Effort test
measure: Calculation of the maximum arteriovenous difference (DAV) : DAV=VO2/Q
time frame: Day 0
description: Effort test
measure: Calculation of maximum muscle diffusion (DM) using the equation of Fick: DM = (Q x DAV)/(200-DAV)
time frame: Day 0
description: Effort test
measure: Peripheral muscular oxygenation
time frame: Day 0
description: Measurement of peripheral muscular oxygenation during the effort test.
measure: Systolic ejection volume at the peak of the effort during the effort test
time frame: Day 0
description: Evaluation of cardiac performance by the value of the systolic ejection volume at the peak of the effort.
The systolic ejection volume is measured beat per beat during the effort test.
measure: Ejection fraction of the left ventricle
time frame: Day 0
description: Measurement of the ejection fraction of the left ventricle in Simpson biplane and the longitudinal strain of the left ventricle in echocardiography.
measure: Metabolic pathways of myoblasts
time frame: From study start until 26 months
description: Myoblasts will be incubated in the presence of stable isotope-labeled tracers. The natural metabolites labelled with stable isotopes will be dosed. The acylcarnitines will be dosed on a mass spectrometer. The Krebs cycle intermediates will be measured in gas chromatography coupled with mass spectrometry.
measure: Presence of cardiomyopathy
time frame: Day 0
description: Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism.
measure: Age of onset of disease (neonatal, < 2 years, 2 - 10 years, > 10 years)
time frame: Day 0
description: Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism.
measure: Number of acute episodes of rhabdomyolyses
time frame: Day 0
description: Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism.
measure: Character of mutations nonsense or missense of the hereditary disease of metabolism
time frame: Day 0
description: Genotypic severity of rhabdomyolysis linked to a hereditary disease of metabolism.
Information available in the patient medical record.
arm group label: Rhabdomyolysis with myoblasts back up
description: Patients with a rhabdomyolysis linked to a hereditary disease of metabolism who have benefited from a diagnostically muscle biopsy and whose myoblasts are available.
Patients benefit from an effort test as part of their care.
arm group label: Rhabdomyolysis
description: Patients with a rhabdomyolysis linked to a hereditary disease of metabolism who have benefited or not from a diagnostically muscle biopsy but whose myoblasts are not available.
Patients benefit from an effort test as part of their care.
arm group label: Witness patients : effort test
description: 10 patient-matched healthy controls for age and sex having performed an effort test and cardiac exploration as part of their care.
arm group label: Witness patients : myoblasts
description: 6 healthy controls matched by age and sex having performed a muscle biopsy as part of their care and whose myoblasts are kept.
intervention type: Other
intervention name: Effort test
description: Cardiac function:
Echocardiography: left ventricular ejection fraction and global longitudinal strain will be measured.
Cardiopulmonary exercise test (CPET): left ventricular stroke volume was assessed noninvasively using a thoracic bioelectrical impedance device : maximal stroke volume at the peak of effort will be considered.
Peripheral muscle function:
CPET: Oxygen uptake (VO2) (and carbon dioxide) output are measured. The slope of the relationship (dQ/dVO2) will be calculated between cardiac output (Q) and VO2 using measurements of Q (using measure of the stroke volume by thoracic bioelectrical impedance device) and VO2 at rest as well as during submaximal and maximal exercise
Muscle oxygenation is measured using a near-infrared spectroscopy device.
VO2 et Q will be measured : dQ/dVO2 is high in case of oxydation defect; If Q is low because of a concommittant cardiac impairement, the DAV = VO2/Q, and DO = (Q x DAV) / (200 - DAV) will be calculated.
arm group label: Rhabdomyolysis
arm group label: Rhabdomyolysis with myoblasts back up
arm group label: Witness patients : effort test
intervention type: Other
intervention name: Functional tests on fibroblasts
description: Functional tests performed on fibroblasts in primary culture, using as tracers of stable isotope-labeled substrates. The metabolites of interest are assayed in mass spectrometry.
arm group label: Rhabdomyolysis with myoblasts back up
arm group label: Witness patients : myoblasts
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: 75 Years
healthy volunteers: No
last name: Pascale de Lonlay
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Antoine Legendre, MD, PhD
role: Study Chair
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Florence Habarou, MD, PhD
role: Study Chair
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Caroline Tuchmann-Durand, Pharm. D, PhD
role: Study Chair
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Rhabdomyolysis
mesh term: Genetic Diseases, Inborn