<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/NCT03236571</url>
  </required_header>
  <id_info>
    <org_study_id>RC31/17/0257</org_study_id>
    <nct_id>NCT03236571</nct_id>
  </id_info>
  <brief_title>Cardiorespiratory and Muscular Rehabilitation of Children and Young Adults With Marfan Syndrome.</brief_title>
  <acronym>Marfanpower</acronym>
  <official_title>Cardiorespiratory and Muscular Rehabilitation of Children and Young Adults With Marfan Syndrome: an Interventional, Prospective, Monocentric Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</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>
      Marfan syndrome (MFS) is a rare genetic disease (1/5000) characterized by the association of&#xD;
      ocular impairment, cardiovascular disease and musculoskeletal disease.&#xD;
&#xD;
      In some chronic conditions, physical activity and training have been shown to be effective in&#xD;
      improving muscle strength and functional abilities but also fatigue and quality of life. We&#xD;
      hypothesize that the implementation of a personalized exercise rehabilitation program&#xD;
      (Personalized Training Program) in children and young adults with MFS, by improving muscle&#xD;
      mass, physical endurance, muscle strength, bone mass and quality of life of these patients.&#xD;
      In order to test this hypothesis, investigators wish to carry out an interventional,&#xD;
      prospective, monocentric study for the first time in children and young adults (&lt;25 years&#xD;
      old) presenting an MFS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Marfan syndrome (MFS) is a rare genetic disease (1/5000) characterized by the association of&#xD;
      ocular impairment, cardiovascular disease and musculoskeletal disease. Chronic fatigue and&#xD;
      decreased physical endurance are almost constant complaints of patients with MFS (90%&#xD;
      according to some studies), and have an impact on activities of daily living and quality of&#xD;
      life. The fragility of the connective tissues and the muscle deficit, responsible for&#xD;
      increased stress on the musculoskeletal system, may be involved in this symptomatology. This&#xD;
      deficiency in muscle mass is already present in young children and worsens in adolescents and&#xD;
      young adults, as researchers have shown in a clinical study carried out in the Toulouse MFS&#xD;
      competence center. This muscle deficit may also explain, at least in part, the deficit in&#xD;
      bone mass observed in children and adults.&#xD;
&#xD;
      In some chronic conditions, physical activity and training have been shown to be effective in&#xD;
      improving muscle strength and functional abilities but also fatigue and quality of life.&#xD;
      Investigators hypothesize that the implementation of a personalized exercise rehabilitation&#xD;
      program (Personalized Training Program) in children and young adults with MFS, by improving&#xD;
      muscle mass, physical endurance, muscle strength, bone mass and quality of life of these&#xD;
      patients. In order to test this hypothesis, investigators wish to carry out an&#xD;
      interventional, prospective, monocentric study for the first time in children and young&#xD;
      adults (&lt;25 years old) presenting an MFS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 24, 2018</start_date>
  <completion_date type="Actual">June 21, 2022</completion_date>
  <primary_completion_date type="Actual">June 21, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of the maximum endurance capacities.</measure>
    <time_frame>Month 9</time_frame>
    <description>Reflected by the maximal oxygen consumption (VO2 peak) during an exercise test. The values of VO2 peak will be compared between the beginning and the end of the rehabilitation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fatigability with effort and quality of life.</measure>
    <time_frame>Month 9</time_frame>
    <description>Questionnaires and self-assessment test. It will be compared between the beginning and the end of the rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscular force.</measure>
    <time_frame>Month 9</time_frame>
    <description>Static evaluation (handgrip) and dynamic evaluation by mechanography. It will be compared between the beginning and the end of the rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition (muscle mass and bone mass).</measure>
    <time_frame>Month 9</time_frame>
    <description>Bone mineral content, bone mineral density of the entire body and lumbar spine (L2-L4), and muscle mass evaluated by dual-energy xray absorptiometry. It will be compared between the beginning and the end of the rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aortic dilation and myocardial function.</measure>
    <time_frame>Month 9</time_frame>
    <description>Assessed by a cardiac ultrasound 2D and 2D strain. It will be compared between the beginning and the end of the rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial function.</measure>
    <time_frame>Month 9</time_frame>
    <description>Assessed by a high resolution vascular ultrasound. It will be compared between the beginning and the end of the rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance.</measure>
    <time_frame>Month 9</time_frame>
    <description>Assessed by questionnaires. It will be compared between the beginning and the end of the rehabilitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac adverse events.</measure>
    <time_frame>Month 9</time_frame>
    <description>Evolution of the aorta dimensions, evaluated by ultrasound. It will be compared between the beginning and the end of the rehabilitation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Marfan Syndrome</condition>
  <arm_group>
    <arm_group_label>Rehabilitation Program</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>It will consist of 2 sessions of 40 minutes per week, for 12 weeks on ergometric bicycle. Each session of 40 min will include 5 minutes of warm-up, 5 minutes of recovery and 6 sequences of 5 min. Each 5-minute sequence will alternate between 4 minutes of pedaling at a load corresponding to the 1st ventilatory threshold (determined in the initial maximum cardiorespiratory effort test) and 1 minute of pedaling at a load corresponding to 2nd ventilatory threshold (determined in the initial maximum cardiopulmonary stress test).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Rehabilitation program</intervention_name>
    <description>The rehabilitation program will consist of a Personalized Training Program and a muscle building program.</description>
    <arm_group_label>Rehabilitation Program</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Marfan syndrome according to Ghent criteria.&#xD;
&#xD;
          -  For minors, signed informed consent of at least one of the holders of the parental&#xD;
             authority. For majors, signed informed consent.&#xD;
&#xD;
          -  Patient affiliated to a social security scheme or equivalent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Cardiac contraindications to Personal Training Program: O Severe aorta dilatation (aortic&#xD;
        diameter&gt; 45 mm) O and / or left ventricular failure (left ventricular ejection fraction&#xD;
        &lt;45%) O and / or severe mitral leakage ≥ grade 3&#xD;
&#xD;
        - Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Edouard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Toulouse</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Toulouse</name>
      <address>
        <city>Toulouse</city>
        <state>Midi-Pyrénées</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Judge DP, Dietz HC. Marfan's syndrome. Lancet. 2005 Dec 3;366(9501):1965-76. doi: 10.1016/S0140-6736(05)67789-6.</citation>
    <PMID>16325700</PMID>
  </reference>
  <reference>
    <citation>De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996 Apr 24;62(4):417-26. doi: 10.1002/(SICI)1096-8628(19960424)62:43.0.CO;2-R.</citation>
    <PMID>8723076</PMID>
  </reference>
  <reference>
    <citation>Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-85. doi: 10.1136/jmg.2009.072785.</citation>
    <PMID>20591885</PMID>
  </reference>
  <reference>
    <citation>Bathen T, Velvin G, Rand-Hendriksen S, Robinson HS. Fatigue in adults with Marfan syndrome, occurrence and associations to pain and other factors. Am J Med Genet A. 2014 Aug;164A(8):1931-9. doi: 10.1002/ajmg.a.36574. Epub 2014 Apr 9.</citation>
    <PMID>24719044</PMID>
  </reference>
  <reference>
    <citation>Giske L, Stanghelle JK, Rand-Hendrikssen S, Strom V, Wilhelmsen JE, Roe C. Pulmonary function, working capacity and strength in young adults with Marfan syndrome. J Rehabil Med. 2003 Sep;35(5):221-8. doi: 10.1080/16501970306095.</citation>
    <PMID>14582554</PMID>
  </reference>
  <reference>
    <citation>Percheron G, Fayet G, Ningler T, Le Parc JM, Denot-Ledunois S, Leroy M, Raffestin B, Jondeau G. Muscle strength and body composition in adult women with Marfan syndrome. Rheumatology (Oxford). 2007 Jun;46(6):957-62. doi: 10.1093/rheumatology/kel450. Epub 2007 Feb 28.</citation>
    <PMID>17329351</PMID>
  </reference>
  <reference>
    <citation>Behan WM, Longman C, Petty RK, Comeglio P, Child AH, Boxer M, Foskett P, Harriman DG. Muscle fibrillin deficiency in Marfan's syndrome myopathy. J Neurol Neurosurg Psychiatry. 2003 May;74(5):633-8. doi: 10.1136/jnnp.74.5.633.</citation>
    <PMID>12700307</PMID>
  </reference>
  <reference>
    <citation>Haine E, Salles JP, Khau Van Kien P, Conte-Auriol F, Gennero I, Plancke A, Julia S, Dulac Y, Tauber M, Edouard T. Muscle and Bone Impairment in Children With Marfan Syndrome: Correlation With Age and FBN1 Genotype. J Bone Miner Res. 2015 Aug;30(8):1369-76. doi: 10.1002/jbmr.2471. Epub 2015 May 14.</citation>
    <PMID>25656438</PMID>
  </reference>
  <reference>
    <citation>Burks TN, Andres-Mateos E, Marx R, Mejias R, Van Erp C, Simmers JL, Walston JD, Ward CW, Cohn RD. Losartan restores skeletal muscle remodeling and protects against disuse atrophy in sarcopenia. Sci Transl Med. 2011 May 11;3(82):82ra37. doi: 10.1126/scitranslmed.3002227.</citation>
    <PMID>21562229</PMID>
  </reference>
  <reference>
    <citation>Peters KF, Horne R, Kong F, Francomano CA, Biesecker BB. Living with Marfan syndrome II. Medication adherence and physical activity modification. Clin Genet. 2001 Oct;60(4):283-92. doi: 10.1034/j.1399-0004.2001.600406.x.</citation>
    <PMID>11683774</PMID>
  </reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>July 18, 2022</last_update_submitted>
  <last_update_submitted_qc>July 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Marfan syndrome</keyword>
  <keyword>Personal Training Program</keyword>
  <keyword>Cardiorespiratory rehabilitation</keyword>
  <keyword>Muscular rehabilitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Marfan Syndrome</mesh_term>
    <mesh_term>Arachnodactyly</mesh_term>
    <mesh_term>Syndrome</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/NCT03236571
org study id: RC31/17/0257
nct id: NCT03236571
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Marfan syndrome (MFS) is a rare genetic disease (1/5000) characterized by the association of
      ocular impairment, cardiovascular disease and musculoskeletal disease.

      In some chronic conditions, physical activity and training have been shown to be effective in
      improving muscle strength and functional abilities but also fatigue and quality of life. We
      hypothesize that the implementation of a personalized exercise rehabilitation program
      (Personalized Training Program) in children and young adults with MFS, by improving muscle
      mass, physical endurance, muscle strength, bone mass and quality of life of these patients.
      In order to test this hypothesis, investigators wish to carry out an interventional,
      prospective, monocentric study for the first time in children and young adults (<25 years
      old) presenting an MFS.
Marfan syndrome (MFS) is a rare genetic disease (1/5000) characterized by the association of
      ocular impairment, cardiovascular disease and musculoskeletal disease. Chronic fatigue and
      decreased physical endurance are almost constant complaints of patients with MFS (90%
      according to some studies), and have an impact on activities of daily living and quality of
      life. The fragility of the connective tissues and the muscle deficit, responsible for
      increased stress on the musculoskeletal system, may be involved in this symptomatology. This
      deficiency in muscle mass is already present in young children and worsens in adolescents and
      young adults, as researchers have shown in a clinical study carried out in the Toulouse MFS
      competence center. This muscle deficit may also explain, at least in part, the deficit in
      bone mass observed in children and adults.

      In some chronic conditions, physical activity and training have been shown to be effective in
      improving muscle strength and functional abilities but also fatigue and quality of life.
      Investigators hypothesize that the implementation of a personalized exercise rehabilitation
      program (Personalized Training Program) in children and young adults with MFS, by improving
      muscle mass, physical endurance, muscle strength, bone mass and quality of life of these
      patients. In order to test this hypothesis, investigators wish to carry out an
      interventional, prospective, monocentric study for the first time in children and young
      adults (<25 years old) presenting an MFS.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Measurement of the maximum endurance capacities.
time frame: Month 9
description: Reflected by the maximal oxygen consumption (VO2 peak) during an exercise test. The values of VO2 peak will be compared between the beginning and the end of the rehabilitation.
measure: Fatigability with effort and quality of life.
time frame: Month 9
description: Questionnaires and self-assessment test. It will be compared between the beginning and the end of the rehabilitation.
measure: Muscular force.
time frame: Month 9
description: Static evaluation (handgrip) and dynamic evaluation by mechanography. It will be compared between the beginning and the end of the rehabilitation.
measure: Body composition (muscle mass and bone mass).
time frame: Month 9
description: Bone mineral content, bone mineral density of the entire body and lumbar spine (L2-L4), and muscle mass evaluated by dual-energy xray absorptiometry. It will be compared between the beginning and the end of the rehabilitation.
measure: Aortic dilation and myocardial function.
time frame: Month 9
description: Assessed by a cardiac ultrasound 2D and 2D strain. It will be compared between the beginning and the end of the rehabilitation.
measure: Endothelial function.
time frame: Month 9
description: Assessed by a high resolution vascular ultrasound. It will be compared between the beginning and the end of the rehabilitation.
measure: Compliance.
time frame: Month 9
description: Assessed by questionnaires. It will be compared between the beginning and the end of the rehabilitation.
measure: Cardiac adverse events.
time frame: Month 9
description: Evolution of the aorta dimensions, evaluated by ultrasound. It will be compared between the beginning and the end of the rehabilitation.
arm group label: Rehabilitation Program
arm group type: Experimental
description: It will consist of 2 sessions of 40 minutes per week, for 12 weeks on ergometric bicycle. Each session of 40 min will include 5 minutes of warm-up, 5 minutes of recovery and 6 sequences of 5 min. Each 5-minute sequence will alternate between 4 minutes of pedaling at a load corresponding to the 1st ventilatory threshold (determined in the initial maximum cardiorespiratory effort test) and 1 minute of pedaling at a load corresponding to 2nd ventilatory threshold (determined in the initial maximum cardiopulmonary stress test).
intervention type: Device
intervention name: Rehabilitation program
description: The rehabilitation program will consist of a Personalized Training Program and a muscle building program.
arm group label: Rehabilitation Program
criteria: 
gender: All
minimum age: 7 Years
maximum age: 25 Years
healthy volunteers: No
last name: Thomas Edouard, MD
role: Principal Investigator
affiliation: CHU Toulouse
facility: 
country: France
citation: Judge DP, Dietz HC. Marfan's syndrome. Lancet. 2005 Dec 3;366(9501):1965-76. doi: 10.1016/S0140-6736(05)67789-6.
PMID: 16325700
citation: De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996 Apr 24;62(4):417-26. doi: 10.1002/(SICI)1096-8628(19960424)62:43.0.CO;2-R.
PMID: 8723076
citation: Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-85. doi: 10.1136/jmg.2009.072785.
PMID: 20591885
citation: Bathen T, Velvin G, Rand-Hendriksen S, Robinson HS. Fatigue in adults with Marfan syndrome, occurrence and associations to pain and other factors. Am J Med Genet A. 2014 Aug;164A(8):1931-9. doi: 10.1002/ajmg.a.36574. Epub 2014 Apr 9.
PMID: 24719044
citation: Giske L, Stanghelle JK, Rand-Hendrikssen S, Strom V, Wilhelmsen JE, Roe C. Pulmonary function, working capacity and strength in young adults with Marfan syndrome. J Rehabil Med. 2003 Sep;35(5):221-8. doi: 10.1080/16501970306095.
PMID: 14582554
citation: Percheron G, Fayet G, Ningler T, Le Parc JM, Denot-Ledunois S, Leroy M, Raffestin B, Jondeau G. Muscle strength and body composition in adult women with Marfan syndrome. Rheumatology (Oxford). 2007 Jun;46(6):957-62. doi: 10.1093/rheumatology/kel450. Epub 2007 Feb 28.
PMID: 17329351
citation: Behan WM, Longman C, Petty RK, Comeglio P, Child AH, Boxer M, Foskett P, Harriman DG. Muscle fibrillin deficiency in Marfan's syndrome myopathy. J Neurol Neurosurg Psychiatry. 2003 May;74(5):633-8. doi: 10.1136/jnnp.74.5.633.
PMID: 12700307
citation: Haine E, Salles JP, Khau Van Kien P, Conte-Auriol F, Gennero I, Plancke A, Julia S, Dulac Y, Tauber M, Edouard T. Muscle and Bone Impairment in Children With Marfan Syndrome: Correlation With Age and FBN1 Genotype. J Bone Miner Res. 2015 Aug;30(8):1369-76. doi: 10.1002/jbmr.2471. Epub 2015 May 14.
PMID: 25656438
citation: Burks TN, Andres-Mateos E, Marx R, Mejias R, Van Erp C, Simmers JL, Walston JD, Ward CW, Cohn RD. Losartan restores skeletal muscle remodeling and protects against disuse atrophy in sarcopenia. Sci Transl Med. 2011 May 11;3(82):82ra37. doi: 10.1126/scitranslmed.3002227.
PMID: 21562229
citation: Peters KF, Horne R, Kong F, Francomano CA, Biesecker BB. Living with Marfan syndrome II. Medication adherence and physical activity modification. Clin Genet. 2001 Oct;60(4):283-92. doi: 10.1034/j.1399-0004.2001.600406.x.
PMID: 11683774
responsible party type: Sponsor
mesh term: Marfan Syndrome
mesh term: Arachnodactyly
mesh term: Syndrome