Marfan Syndrome Moderate Exercise Pilot

Marfan Syndrome Clinical Trial

Official title:

Evaluating the Effects of Moderate Physical Activity on Health and Well-being in Adolescents and Young Adults With Marfan Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04641325
• Other study ID #: H-45475
• Status: Completed
• Phase: N/A
• Start date: November 9, 2020
• Est. completion date: December 20, 2022

Study information

• Verified date: August 2023
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: December 20, 2022
• Est. primary completion date: October 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Marfan Syndrome
• Syndrome

Intervention

Other:
• Exercise Intervention Group
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.

Locations

Country	Name	City	State
United States	Texas Children's Hospital	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor College of Medicine	The Marfan Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum VO2	Maximum VO2 in ml/kg/minute will be collected via Exercise Stress Test. Range 30-85, higher is better.	4 months
Secondary	Mean systolic blood pressure	mmHg, range 70-200, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile	4 months
Secondary	Mean Diastolic blood pressure	mmHg, range 20-150, both low and high are abnormal, goal is age, sex and height-based, goal 10-50 percentile	4 months
Secondary	Mean pulse pressure	mmHg, systolic blood pressure minus diastolic blood pressure, range 30-70 mmHg, goal is normal range for age and sex	4 months
Secondary	Weight	kg, range 50-300kg, lower is better, excluding underweight patients	4 months
Secondary	BMI	kg/m2, lower is better generally, excluding pts with BMI <5% for age	4 months
Secondary	Left ventricular strain by cardiac MRI	Continuous measure derived from post-processing MRI	4 months
Secondary	Right ventricular strain by cardiac MRI	Continuous measure derived from post-processing MRI	4 months
Secondary	Aortic root strain	Continuous measure %, higher is less stiff, Range 0-40	4 months
Secondary	Aortic Root Distensibility	×10-3 mm Hg-1, Continuous measure, range 0.1-10	4 months
Secondary	Aortic Root ß-Stiffness index	No units, Range 0.1-90	4 months
Secondary	Maximum aortic root dimension	Measured in cm, range 1-8cm	4 months
Secondary	Aortic root z-score	No units, based on body surface area published references, range -3 to 25	4 months
Secondary	Aortic pulse wave velocity from MRI	meters/second, range 0-30	4 months
Secondary	Pulse wave velocity derived from applanation tonometry	meters/second, range 0-30	4 months
Secondary	Augmentation index	%, range 1-90	4 months
Secondary	Manual muscle testing score	Grade 0-5, higher is better	4 months
Secondary	Reactive hyperemia index	no units, 0-4 range, higher is worse	4 months
Secondary	Visual analog assessment of pain	no units, scale from 0-6, 6 is worse	4 months
Secondary	Single Leg Stance Test	seconds, higher is better	4 months
Secondary	Single limb squat test score	seconds, higher is better	4 months
Secondary	Star Excursion Balance Test	%, range 0-100, higher is better	4 months
Secondary	6M Timed Hop Test	milliseconds, range 1 to infinity, lower is better	4 months
Secondary	Scale for Child Anxiety Related Emotional Disorders (SCARED) (ages 12-18 y)	41 item scale, each with 3 point Likert scale, scale is summed, range 0-123, higher is worse	4 months
Secondary	Quality of Life Scale (QOLS) (ages 19-21 y)	16 items, each with 7 point Likert, higher is worse	4 months
Secondary	Pediatric Quality of Life Scale (PedsQL) scale scores	reported in 3 domains, each reported on Likert scale, scaled to 0-100 scale, lower is worse	4 months
Secondary	Children's Depression Inventory (CDI) 2 (ages 12-18 y)	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	4 months
Secondary	Depression, Anxiety, & Stress Scale (DASS) (ages 19-21 y)	set of 3 self-report scales. Each scale contains 14 items, each with a 4-point severity/frequency scale, higher is worse	4 months