Towards Optimal Treatment of Marfan Syndrome (TOWER)

The purpose of this study is to determine whether new magnetic resonance imaging techniques can be used as a biomarker of aortic disease severity in patients with Marfan syndrome.

Study Overview

• Status: Completed
• Conditions: Marfan Syndrome
• Intervention / Treatment: Other: Magnetic Resonance imaging (MRI) examination

• Study Type: Observational
• Enrollment (Actual): 148

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC, location AMC
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud University Medical Center
  • Noord-Holland
    • Leiden, Noord-Holland, Netherlands, 2333 ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

All Marfan syndrome patients age 18-50 with a known FBN1 mutation are eligeble for participation. Only patients who are unable to undergo an MRI examination are excluded.

Description

Inclusion Criteria:

• MFS patients with a known FBN1 mutation
• Between 18-50 years of age

Exclusion Criteria:

• Contraindication for MR imaging
• Mental retardation
• Pregnancy, or planned pregnancy during study period

Additional exclusion criteria healthy controls:

- History of aorta disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Marfan Syndrome patients; Marfan Syndrome patients age 18-50 with a pathological FBN1 mutation	Other: Magnetic Resonance imaging (MRI) examination; 3D CINE and 4 dimensional (4D) flow MRI sequence
Healthy volunteers; Age and gender matched healthy control patients without a history of aortic disease.	Other: Magnetic Resonance imaging (MRI) examination; 3D CINE and 4 dimensional (4D) flow MRI sequence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in 3D aortic displacement in millimeters between Marfan patients (MFS) and healthy volunteers.	aortic displacement in the thoracic aorta. normal values unknown, but single paper: Marfan patients range: 1.77 to 10.03 millimeters, volunteers 7.34 ± 1.69 millimeters. lower is worse.	Baseline
Difference in pulse wave velocity, in meters per second between Marfan patients and healthy volunteers.	pulse wave velocity expressed in m/s in the thoracic aorta, normal values age dependent: but range +/- 4 - 30 m/s, higher is worse	Baseline
Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients and healthy volunteers	oscillatory shear index (dimensionless) in the thoracic aorta, range between 0 - 0.5 (No normal values defined), higher is worse	Baseline
Change in aortic displacement expressed in millimeters , between MFS patient aortas prior to compared to after PEARS procedure or conventional aortic surgery.	aortic displacement expressed in millimeters in the thoracic aorta. Pre-post change unknown, however operated 3.60 +/- 1.0 millimeter versus native aorta 7.01 +/- 3.09 millimeters. Lower is worse	Change from baseline to 6 months after surgery
Change in aortic pulse wave velocity (meters/second), between MFS patient aortas prior to compared to after PEARS procedure or conventional aortic surgery.	pulse wave velocity in the thoracic aorta expressed in meters/second. Higher is worse. normal values for change unknown.	Change from baseline to 6 months after surgery
Change in oscillatory shear index (dimensionless) between MFS patient aortas prior to compared to after PEARS procedure or conventional aortic surgery.	oscillatory shear index (dimensionless) in the thoracic aorta. Higher is worse range between 0 -5.	Change from baseline to 6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in 3D aortic displacement expressed in mm between Marfan patients with and without a native aorta	aortic displacement in the thoracic aorta, lower is worse. operated 3.60 +/- 1.0 millimeter versus native aorta 7.01 +/- 3.09 millimeters	Baseline
Difference in 3D aortic displacement expressed in mm between Marfan patients with aortic root diameter >4.5cm versus <4.5 cm	aortic displacement in the thoracic aorta, lower is worse. Normal values unknown.	Baseline
Difference in 3D aortic displacement expressed in mm between Marfan patients with a haploinsufficient fibrillin 1 mutation versus dominant negative mutation	aortic displacement in the thoracic aorta. Lower is worse. Normal values unknown.	Baseline
Difference in 3D aortic displacement expressed in mm between male versus female Marfan patients	aortic displacement in the thoracic aorta,Lower is worse. Normal values unknown.	Baseline
Difference in 3D aortic displacement expressed in mm between Marfan patients based on antihypertensive medication used	aortic displacement in the thoracic aorta, Lower is worse. Normal values unknown.	Baseline
Difference in pulse wave velocity, expressed in meters per second between Marfan patients with and without a native aorta	pulse wave velocity expressed in m/s in the thoracic aorta, Lower is worse. Normal values unknown. Single study in general aneurysm population: pre surgery: 18.0 +/-4.0 meters per second post surgery 20.6 +/- 6.0 meters per second. higher is worse	Baseline
Difference in pulse wave velocity, expressed in m/s between Marfan patients with an aortic root diameter >4.5 cm versus <4.5 cm	pulse wave velocity expressed in m/s in the thoracic aorta. Higher is worse. Normal values unknown.	Baseline
Difference in pulse wave velocity, expressed in m/s between Marfan patients with a haploinsufficient fibrillin-1 mutation versus a dominant negative mutation	pulse wave velocity expressed in m/s in the thoracic aorta. Higher is worse. Normal values unknown.	Baseline
Difference in pulse wave velocity, expressed in m/s between male and female Marfan patients	pulse wave velocity expressed in m/s in the thoracic aorta Higher is worse. Normal values unknown.	Baseline
Difference in pulse wave velocity, expressed in m/s between Marfan patients based on antihypertensive medication used	pulse wave velocity expressed in m/s in the thoracic aorta	Baseline
Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients with and without a native aorta	oscillatory shear index (dimensionless) in the thoracic aorta. Higher is worse. Normal values unknown.	Baseline
Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients with aortic root diameter >4.5cm versus <4.5 cm	oscillatory shear index (dimensionless) in the thoracic aorta. Higher is worse. Normal values unknown.	Baseline
Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients with a haploinsufficient fibrillin 1 mutation versus dominant negative mutation	oscillatory shear index (dimensionless) in the thoracic aorta. Higher is worse. Normal values unknown.	Baseline
Difference in oscillatory shear index (dimensionless) expressed in m/s between male versus female Marfan patients	oscillatory shear index (dimensionless) in the thoracic aorta. Higher is worse. Normal values unknown.	Baseline
Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients based on antihypertensive medication used	oscillatory shear index (dimensionless) in the thoracic aorta. Higher is worse. Normal values unknown.	Baseline
The correlation between regional wall shear stress and elastic fibre thickness in resected aorta tissue of MFS patients.	Correlation of locally MRI measured wall shear stress and histologic findings in the thoracic aorta. Neither is worse. Normal values dependent on location of measurement, exploratory outcome. .	Baseline MRI with aortic surgery tissue

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Netherlands Organisation for Scientific Research
• Investigators: Principal Investigator: Pim Ooij, PhD, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2023
• Primary Completion (Actual): April 16, 2025
• Study Completion (Actual): April 16, 2025

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 13, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Aortic disease
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Disease; Musculoskeletal Abnormalities; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Abnormalities, Multiple; Bone Diseases, Developmental; Limb Deformities, Congenital; Syndrome; Marfan Syndrome; Arachnodactyly
• Other Study ID Numbers: NL82669.018.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared

Drug and device information, study documents

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