TOWER: Towards Optimal Treatment of Marfan Syndrome

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05944614
• Collaborator: Netherlands Organisation for Scientific Research (Other)
• Enrollment: 150
• Locations: 4
• Anticipated Duration (Months): 27.2
• Patients Per Site: 37.5
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Marfan Syndrome	Other: Magnetic Resonance imaging examination

Study Design

• Study Type: Observational
• Anticipated Enrollment: 150 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Towards Optimal Treatment of Marfan Syndrome
• Actual Study Start Date: Feb 23, 2023
• Anticipated Primary Completion Date: Jun 1, 2025
• Anticipated Study Completion Date: Jun 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Difference in 3D aortic displacement expressed in mm between Marfan patients and healthy volunteers [Baseline]

   aortic displacement in the thoracic aorta

2. Difference in pulse wave velocity, expressed in m/s between Marfan patients and healthy volunteers [Baseline]

   pulse wave velocity expressed in m/s in the thoracic aorta

3. Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients and healthy volunteers [Baseline]

   oscillatory shear index (dimensionless) in the thoracic aorta

4. Change in aortic displacement expressed in mm, between MFS patient aortas prior to compared to after PEARS procedure or conventional aortic surgery. [Change from baseline to 6 months after surgery]

   aortic displacement expressed in mm in the thoracic aorta

5. Change in aortic pulse wave velocity, between MFS patient aortas prior to compared to after PEARS procedure or conventional aortic surgery. [Change from baseline to 6 months after surgery]

   pulse wave velocity in the thoracic aorta

6. Change in oscillatory shear index (dimensionless) between MFS patient aortas prior to compared to after PEARS procedure or conventional aortic surgery. [Change from baseline to 6 months after surgery]

   oscillatory shear index (dimensionless) in the thoracic aorta

Secondary Outcome Measures

1. Difference in 3D aortic displacement expressed in mm between Marfan patients with and without a native aorta [Baseline]

   aortic displacement in the thoracic aorta

2. Difference in 3D aortic displacement expressed in mm between Marfan patients with aortic root diameter >4.5cm versus <4.5 cm [Baseline]

   aortic displacement in the thoracic aorta

3. Difference in 3D aortic displacement expressed in mm between Marfan patients with a haploinsufficient fibrillin 1 mutation versus dominant negative mutation [Baseline]

   aortic displacement in the thoracic aorta

4. Difference in 3D aortic displacement expressed in mm between male versus female Marfan patients [Baseline]

   aortic displacement in the thoracic aorta

5. Difference in 3D aortic displacement expressed in mm between Marfan patients based on anithypertensive medication used [Baseline]

   aortic displacement in the thoracic aorta

6. Difference in pulse wave velocity, expressed in m/s between Marfan patients with and without a native aorta [Baseline]

   pulse wave velocity expressed in m/s in the thoracic aorta

7. Difference in pulse wave velocity, expressed in m/s between Marfan patients with an aortic root diameter >4.5 cm versus <4.5 cm [Baseline]

   pulse wave velocity expressed in m/s in the thoracic aorta

8. Difference in pulse wave velocity, expressed in m/s between Marfan patients with a haploinsufficient fibrillin-1 mutation versus a dominant negative mutation [Baseline]

   pulse wave velocity expressed in m/s in the thoracic aorta

9. Difference in pulse wave velocity, expressed in m/s between male and female Marfan patients [Baseline]

   pulse wave velocity expressed in m/s in the thoracic aorta

10. Difference in pulse wave velocity, expressed in m/s between Marfan patients based on anithypertensive medication used [Baseline]

    pulse wave velocity expressed in m/s in the thoracic aorta

11. Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients with and without a native aorta [Baseline]

    oscillatory shear index (dimensionless) in the thoracic aorta

12. Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients with aortic root diameter >4.5cm versus <4.5 cm [Baseline]

    oscillatory shear index (dimensionless) in the thoracic aorta

13. Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients with a haploinsufficient fibrillin 1 mutation versus dominant negative mutation [Baseline]

    oscillatory shear index (dimensionless) in the thoracic aorta

14. Difference in oscillatory shear index (dimensionless) expressed in m/s between male versus female Marfan patients [Baseline]

    oscillatory shear index (dimensionless) in the thoracic aorta

15. Difference in oscillatory shear index (dimensionless) expressed in m/s between Marfan patients based on anithypertensive medication used [Baseline]

    oscillatory shear index (dimensionless) in the thoracic aorta

16. The correlation between regional wall shear stress and elastic fibre thickness in resected aorta tissue of MFS patients. [Baseline MRI with aortic surgery tissue]

    Correlation of locally MRI measured wall shear stress and histologic findings in the thoracic aorta

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboud University Medical Center	Nijmegen	Gelderland	Netherlands	6525 GA
2	Amsterdam UMC, location AMC	Amsterdam	Meibergdreef 9	Netherlands	1105 AZ
3	Leiden University Medical Center	Leiden	Noord-Holland	Netherlands	2333 ZA
4	University Medical Center Groningen	Groningen		Netherlands	9713 GZ

Sponsors and Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Netherlands Organisation for Scientific Research

Investigators

• Principal Investigator: Pim Ooij, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Ir. Pim van Ooij, Dr. ir., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• ClinicalTrials.gov Identifier: NCT05944614
• Other Study ID Numbers: NL82669.018.22
• First Posted: Jul 13, 2023
• Last Update Posted: Jul 13, 2023
• Last Verified: Jul 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dr. Ir. Pim van Ooij, Dr. ir., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): Magnetic Resonance Imaging; Aortic disease
• Additional relevant MeSH terms: Marfan Syndrome; Arachnodactyly; Syndrome

Study Results

No Results Posted as of Jul 13, 2023