Marfan Syndrome Moderate Exercise Pilot
Condition: Marfan Syndrome
MeSH terms: Marfan Syndrome; Arachnodactyly; Syndrome
Study type: Interventional

Summary: 
      Marfan syndrome (MFS) affects multiple organ systems including the heart, bones, ligaments,
      and eyes, and is associated with significant risk of aortic dissection. Given limited
      evidence from in-vitro studies, and theoretical concerns, the majority of patients with MFS
      are restricted from certain physical activities. The lack of exercise and deconditioning have
      detrimental effects including increasing weakness, joint pain, decreased endurance, and
      depressive symptoms. Given the significant paucity of data currently existing on the effects
      of exercise in humans with MFS, and the recent, optimistic findings in rodent models, this
      pilot trial was established to assess the effects of moderated dynamic exercise in
      adolescents and young adults with MFS.
    

Detailed description: 
      Marfan syndrome (MFS) affects multiple organ systems including the heart, bones, ligaments,
      and eyes, and is associated with significant risk of aortic dissection. Given anecdotal
      reports of aortic dissection, limited evidence from in-vitro studies, and theoretical
      concerns, the majority of patients with MFS are restricted from certain physical activities,
      most commonly isometric exercise and contact sports. Published guidelines also suggest
      restriction from highly dynamic competitive sports. While clinicians may mean to restrict
      patients only from competitive sports, often children and families interpret this caution as
      applying to almost all exercise, resulting in a large number of patients with Marfan syndrome
      being sedentary. This lack of exercise and deconditioning likely have detrimental effects in
      increasing weakness and joint pain and decreasing endurance. Depressive symptoms are also not
      uncommon in Marfan syndrome, and may be triggered or exacerbated by guidance to acutely cease
      participation in sports at the time of diagnosis.

      To date, as far as the investigators are aware, there are no published controlled studies on
      the effects of dynamic exercise on human subjects. In 2017, Mas-Stachurska et al published a
      study suggesting that a moderate level of dynamic exercise mitigated progressive degradation
      of the cardiac structures typically seen in Marfan Syndrome in a rodent sample. This study
      suggests the possibility that the fears surrounding moderate exercise in humans may be
      unwarranted. In addition, this study suggests that moderate exercise may actually protect the
      aorta and myocardium, in addition to the numerous other physical and emotional benefits that
      have been shown to result from consistent exercise. The overall goal is to evaluate the
      effects of a moderate dynamic exercise program on measures of cardiovascular, muscular, and
      mental health in adolescents and young adults with Marfan syndrome. The investigators plan to
      perform a randomized pilot study to calculate effect estimates to perform a larger
      multi-center study. The objective is to 1) randomize 20 patients with Marfan syndrome age
      12-21 years to current status (controls) versus a moderate dynamic exercise intervention,
      then 2) allow the control group patients to undergo the exercise intervention. The
      investigators will then compare outcomes between both the intervention and control groups,
      and between the baseline and post-intervention states. Specific outcome measures will include
      cardiovascular assessment: maximal oxygen uptake (max VO2), segmental and central aortic
      stiffness, ventricular mass and volume, and endothelial function, muscular/physical
      assessment: manual muscle testing (MMT), functional balance, and pain assessment, and quality
      of life/mental health assessment: health-related quality of life, depression and anxiety
      screening scales. The hypothesis is that the intervention of a moderate exercise program
      introduced by a licensed physical therapist will result in improvement in cardiovascular
      status, muscular health, and mental health without detrimental effects on the aortic wall.
    

Intervention name(s): Exercise Intervention Group
Intervention type(s): Other
Intervention description(s): Patients will be educated on methods of self-evaluating exertion and cardiovascular effort by assessing respiratory rate and perceived exertion. Next, patients will be given options for cardiovascular activities and complete at a moderate level of activity for a minimum of 150 minutes per week. Patients will perform a combination of exercises under the supervision of a physical therapist until a mod intensity level is reached and sustained. Patients will be taught to use the activity tracker to record their heart rate, activity, and PES. Patients will have a phone call every week to assess status, answer questions, and provide guidance on progressing intensity or duration of exercise. At the end of 8 weeks all patients will return for re-assessment.
Intervention model: Single Group Assignment
Intervention model description: The first part of trial was a Randomized Controlled Step-Wedge Pilot Trial as below 2 groups (Exercise Intervention Group and Current Care Group) The first phase of the study will maintain the Current Care Group as the control. At the end of the first phase, the Current Care Group will crossover and receive the Exercise Intervention as the second phase of the trial.
With the COVID-19 pandemic causing delays in the study, and decreased enrollment and decreased access to MRI, the study was altered to a single group. comparing the same outcomes at baseline and after the intervention. This eliminates the blinding of the PI, but those interpreting the tests are still blinded.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cardiovascular; Moderate Exercise; Physical Therapy