Marfan Syndrome Moderate Exercise Pilot
- Conditions
- Marfan Syndrome
- Interventions
- Other: Exercise Intervention Group
- Registration Number
- NCT04641325
- Lead Sponsor
- Baylor College of Medicine
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
- 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
- Patients who have undergone aortic surgery
- Patients with major congenital heart disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Exercise Intervention Group Exercise Intervention Group Group of up to 20 patients will receive all of the preliminary outcome measure testing (cardiovascular, musculoskeletal, and psychological screening) in addition to exercise intervention education, demonstration, and follow up to ensure compliance and safety.
- Primary Outcome Measures
Name Time Method Maximum VO2 4 months Maximum VO2 in ml/kg/minute will be collected via Exercise Stress Test. Range 30-85, higher is better.
- Secondary Outcome Measures
Name Time Method BMI 4 months kg/m2, lower is better generally, excluding pts with BMI \<5% for age
Aortic Root β-Stiffness index 4 months No units, Range 0.1-90
Left ventricular strain by cardiac MRI 4 months Continuous measure derived from post-processing MRI
Aortic root strain 4 months Continuous measure %, higher is less stiff, Range 0-40
Aortic Root Distensibility 4 months ×10-3 mm Hg-1, Continuous measure, range 0.1-10
Reactive hyperemia index 4 months no units, 0-4 range, higher is worse
6M Timed Hop Test 4 months milliseconds, range 1 to infinity, lower is better
Weight 4 months kg, range 50-300kg, lower is better, excluding underweight patients
Aortic root z-score 4 months No units, based on body surface area published references, range -3 to 25
Pulse wave velocity derived from applanation tonometry 4 months meters/second, range 0-30
Visual analog assessment of pain 4 months no units, scale from 0-6, 6 is worse
Quality of Life Scale (QOLS) (ages 19-21 y) 4 months 16 items, each with 7 point Likert, higher is worse
Mean Diastolic blood pressure 4 months mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
Right ventricular strain by cardiac MRI 4 months Continuous measure derived from post-processing MRI
Pediatric Quality of Life Scale (PedsQL) scale scores 4 months reported in 3 domains, each reported on Likert scale, scaled to 0-100 scale, lower is worse
Mean systolic blood pressure 4 months mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile
Mean pulse pressure 4 months mmHg, systolic blood pressure minus diastolic blood pressure, range 30-70 mmHg, goal is normal range for age and sex
Maximum aortic root dimension 4 months Measured in cm, range 1-8cm
Aortic pulse wave velocity from MRI 4 months meters/second, range 0-30
Augmentation index 4 months %, range 1-90
Single limb squat test score 4 months seconds, higher is better
Scale for Child Anxiety Related Emotional Disorders (SCARED) (ages 12-18 y) 4 months 41 item scale, each with 3 point Likert scale, scale is summed, range 0-123, higher is worse
Manual muscle testing score 4 months Grade 0-5, higher is better
Single Leg Stance Test 4 months seconds, higher is better
Star Excursion Balance Test 4 months %, range 0-100, higher is better
Depression, Anxiety, & Stress Scale (DASS) (ages 19-21 y) 4 months set of 3 self-report scales. Each scale contains 14 items, each with a 4-point severity/frequency scale, higher is worse
Children's Depression Inventory (CDI) 2 (ages 12-18 y) 4 months 28-item assessment that yields a Total Score, 2 scale scores, and 4 subscale scores. For each item, respondent is presented with 3 choices that correspond to 3 levels of symptomatology: 0 (absence of symptoms), 1 (mild or probable symptom), or 2 (definite symptom). Lower is better
Trial Locations
- Locations (1)
Texas Children's Hospital
🇺🇸Houston, Texas, United States