Clinical trial NCT04641325: Marfan Syndrome Moderate Exercise Pilot
Official title: Evaluating the Effects of Moderate Physical Activity on Health and Well-being in Adolescents and Young Adults With Marfan Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Marfan Syndrome
Keywords: Cardiovascular
Moderate Exercise
Physical Therapy
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: The Marfan Foundation
First posted: 2020-11-23
Enrollment: 23
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Must be between the ages of 12-21
* Diagnosis of Marfan Syndrome
* Must not have other conditions that limit the patients ability to perform exercise

Exclusion Criteria:

* Patients who have undergone aortic surgery
* Patients with major congenital heart disease

Primary outcomes:
measure: Maximum VO2
timeFrame: 4 months
Secondary outcomes:
measure: Mean systolic blood pressure
timeFrame: 4 months
measure: Mean Diastolic blood pressure
timeFrame: 4 months
measure: Mean pulse pressure
timeFrame: 4 months
measure: Weight
timeFrame: 4 months
measure: BMI
timeFrame: 4 months
measure: Left ventricular strain by cardiac MRI
timeFrame: 4 months
measure: Right ventricular strain by cardiac MRI
timeFrame: 4 months
measure: Aortic root strain
timeFrame: 4 months
measure: Aortic Root Distensibility
timeFrame: 4 months
measure: Aortic Root β-Stiffness index
timeFrame: 4 months
measure: Maximum aortic root dimension
timeFrame: 4 months
measure: Aortic root z-score
timeFrame: 4 months
measure: Aortic pulse wave velocity from MRI
timeFrame: 4 months
measure: Pulse wave velocity derived from applanation tonometry
timeFrame: 4 months
measure: Augmentation index
timeFrame: 4 months
measure: Manual muscle testing score
timeFrame: 4 months
measure: Reactive hyperemia index
timeFrame: 4 months
measure: Visual analog assessment of pain
timeFrame: 4 months
measure: Single Leg Stance Test
timeFrame: 4 months
measure: Single limb squat test score
timeFrame: 4 months
measure: Star Excursion Balance Test
timeFrame: 4 months
measure: 6M Timed Hop Test
timeFrame: 4 months
measure: Scale for Child Anxiety Related Emotional Disorders (SCARED) (ages 12-18 y)
timeFrame: 4 months
measure: Quality of Life Scale (QOLS) (ages 19-21 y)
timeFrame: 4 months
measure: Pediatric Quality of Life Scale (PedsQL) scale scores
timeFrame: 4 months
measure: Children's Depression Inventory (CDI) 2 (ages 12-18 y)
timeFrame: 4 months
measure: Depression, Anxiety, & Stress Scale (DASS) (ages 19-21 y)
timeFrame: 4 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Shaine A Morris, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: