Children and Adolescents With Marfan Syndrome: 10,000 Healthy Steps and Beyond

• ClinicalTrials.gov Identifier: NCT03567460
• Recruitment Status: Recruiting
• First Posted: June 25, 2018
• Last Update Posted: September 19, 2019
• Sponsor: Stanford University
• Collaborator: Midwestern University
• Information provided by (Responsible Party): Seda Tierney, Stanford University

Study Description

Brief Summary:

Marfan patients are at risk of sudden death due to weakening of the wall of the large blood vessel leading from the heart (aorta). The wall of the aorta weakens and dilates which can rupture, leading to death, and sometimes during intense exercise.

There is some evidence in Marfan patients that a stiffer aorta increases risk for rupture.

For some time, clinical care has focused on what type of exercise these patients should avoid due to risk for aortic dissection. Little clinical emphasis has been placed on encouraging patients to engage in routine and safe exercise such as walking. Informed by this evidence, the investigators propose to collaboratively investigate whether regular exercise improves aortic health in adolescent Marfan patients.

Condition or disease	Intervention/treatment	Phase
Marfan Syndrome	Behavioral: Exercise	Not Applicable

Detailed Description:

Marfan syndrome is an inherited disorder of the connective tissue, which provides material and support for the skeleton, muscles, and blood vessels. Marfan patients are at risk of sudden death due to weakening of the wall of the large blood vessel leading from the heart (aorta). The wall of the aorta weakens and dilates which can rupture, leading to death, and sometimes during intense exercise.

Typically, the weakening process starts when elastin fibers in the aorta become fragmented. There is some evidence in Marfan patients that a stiffer aorta increases risk for rupture.

For some time, clinical care has focused on what type of exercise these patients should avoid due to risk for aortic dissection. Little clinical emphasis has been placed on encouraging patients to engage in routine and safe exercise such as walking. These young patients also frequently choose sedentary lifestyles, most likely due to limitations imposed by parents as well as adolescents' own perceptions of what is safe for them and their physical capabilities. Another complicating factor is that these patients often experience difficulty coping with their diagnosis. Informed by this evidence, the investigators propose to collaboratively investigate whether regular exercise improves aortic health and coping skills in adolescent Marfan patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 25 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Children and Adolescents With Marfan Syndrome: 10,000 Healthy Steps and Beyond
• Actual Study Start Date: January 1, 2017
• Estimated Primary Completion Date: December 31, 2019
• Estimated Study Completion Date: December 31, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: 10,000 Steps/day for Pediatric Marfan Patients; Participants will be given a Garmin VivoFit and asked to take at least 10,000 steps per day. A study coordinator will reach out at least once per week to check in on progress made and help make weekly goals.

Behavioral: Exercise; Across studies in adolescents in general population, 60 minutes of recommended daily exercise level is achieved, on average, within a total volume of 10,000-11,700 steps. The investigators will assess baseline physical activity quantitatively by using an accelerometer worn on the wrist during waking hours over a 7-day period. Each participant will be given a Garmin device to place on their wrist that will track their steps. Then patients will be asked to complete 10,000 steps daily for 6 months (acclimation over a week), which will be encouraged by daily text messages or e-mail, and weekly phone calls by the intervention team in addition to a Garmin and Facebook peer group.

Outcome Measures

Primary Outcome Measures :

1. To determine if 6 months of regular physical activity improves aortic stiffness in MFS patients. exercise, a decrease in expressed biomarkers, and an increase in COPE scores of MFS patients. [ Time Frame: 6 months of intervention ]
   The investigators' primary outcome measure is aortic stiffness measured by arterial tonometry (pulse wave velocity).

Secondary Outcome Measures :

1. To determine if 6 months of regular physical activity improves aortic stiffness and the biomarker profile in MFS patients. [ Time Frame: 6 months of intervention ]
   The secondary outcomes include aortic stiffness at the aortic root at the level of the sinuses of Valsalva and ascending aorta.
2. To determine if 6 months of regular physical activity improves aortic stiffness and the biomarker profile in MFS patients. [ Time Frame: 6 months of intervention ]
   Secondary outcomes will be expression levels of TGF-β, Ang-II, MMP-2 & -9, ROS levels.
3. To determine if 6 months of regular physical activity decreases aortic stiffness and rate of aortic root dilation in Marfan mice. [ Time Frame: 6 months of intervention ]
   Secondary outcomes will be expression levels of TGF-β, MMP-2, MMP-9, and ROS.
4. To determine if 6 months of regular physical activity improves coping skills in Marfan patients. [ Time Frame: 6 months of intervention ]
   The outcome measure is the COPE inventory score.

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 19 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 10-19 years of age,
2. MFS by revised Ghent criteria,
3. Cardiac clearance to exercise by the primary cardiologist.

Exclusion Criteria:

1. Ventricular dysfunction,
2. Prior history of aortic surgery.

Contacts and Locations

Contacts

Contact: Seda Tierney, MD; (650) 725-8246; tierneys@stanford.edu

Contact: Angela Chen, BS; 650-307-3595; achen11@stanford.edu

Locations

United States, California

Stanford Children's Health; Recruiting

Palo Alto, California, United States, 94306

Contact: Elif Seda M Selamet Tierney 650-736-8716 tierneys@stanford.edu

Sponsors and Collaborators

Stanford University

Midwestern University

Investigators

• Principal Investigator: Seda Tierney, MD; Stanford University

More Information

• Responsible Party: Seda Tierney, Assistant Professor in Pediatrics, Stanford University
• ClinicalTrials.gov Identifier: NCT03567460
• Other Study ID Numbers: 37176
• First Posted: June 25, 2018
• Last Update Posted: September 19, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Marfan Syndrome; Arachnodactyly; Syndrome; Disease; Pathologic Processes; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Abnormalities, Multiple; Congenital Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Limb Deformities, Congenital; Musculoskeletal Abnormalities