Marfan Syndrome Moderate Exercise Pilot

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

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.

Study Overview

• Status: Completed
• Conditions: Marfan Syndrome
• Intervention / Treatment: Other: Exercise Intervention Group

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum VO2	Maximum VO2 in ml/kg/minute will be collected via Exercise Stress Test. Range 30-85, higher is better.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Weight	kg, range 50-300kg, lower is better, excluding underweight patients	4 months
BMI	kg/m2, lower is better generally, excluding pts with BMI <5% for age	4 months
Left ventricular strain by cardiac MRI	Continuous measure derived from post-processing MRI	4 months
Right ventricular strain by cardiac MRI	Continuous measure derived from post-processing MRI	4 months
Aortic root strain	Continuous measure %, higher is less stiff, Range 0-40	4 months
Aortic Root Distensibility	×10-3 mm Hg-1, Continuous measure, range 0.1-10	4 months
Aortic Root β-Stiffness index	No units, Range 0.1-90	4 months
Maximum aortic root dimension	Measured in cm, range 1-8cm	4 months
Aortic root z-score	No units, based on body surface area published references, range -3 to 25	4 months
Aortic pulse wave velocity from MRI	meters/second, range 0-30	4 months
Pulse wave velocity derived from applanation tonometry	meters/second, range 0-30	4 months
Augmentation index	%, range 1-90	4 months
Manual muscle testing score	Grade 0-5, higher is better	4 months
Reactive hyperemia index	no units, 0-4 range, higher is worse	4 months
Visual analog assessment of pain	no units, scale from 0-6, 6 is worse	4 months
Single Leg Stance Test	seconds, higher is better	4 months
Single limb squat test score	seconds, higher is better	4 months
Star Excursion Balance Test	%, range 0-100, higher is better	4 months
6M Timed Hop Test	milliseconds, range 1 to infinity, lower is better	4 months
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
Quality of Life Scale (QOLS) (ages 19-21 y)	16 items, each with 7 point Likert, higher is worse	4 months
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
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
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

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: The Marfan Foundation
• Investigators: Principal Investigator: Shaine A Morris, MD MPH, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Actual): October 30, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Physical Therapy; Cardiovascular; Moderate Exercise
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Bone Diseases, Developmental; Limb Deformities, Congenital; Syndrome; Marfan Syndrome; Arachnodactyly
• Other Study ID Numbers: H-45475

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No