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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04641325
Other study ID # H-45475
Secondary ID
Status Completed
Phase N/A
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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