Lymphedema, Low-grade Inflammation and the Vasculature in Turner Syndrome
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University of Aarhus
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Detecting low-grade inflammation in Turner Syndrome preforming FDG-PET/CT-scans to locate low grade inflammation.
Study Overview
Brief Summary
100 women with karyotype verified TS, previously examined at 4 study visits during a 19-year period will be asked to participate in a 5th study visit. Healthy age-matched females will be included as controls in a ratio 2:1.
The aim is to examine and quantify the cardiovascular and lymphatic system in women with TS. The investigators will study a possible causal mechanism between the known pathologic phenotype and alterations in these systems to understand, prevent or treat the life-threatening complications in TS.
Detailed Description
Background:
Patients with Turner syndrome (TS) are at risk of many complications during childhood, adolescence, and adulthood, including reduced final height, estrogen deficiency, infertility, lymphedema, ischemic heart disease, aortic dilation and dissection, congenital heart defect, hypertension, stroke, and autoimmune diseases in general.
The aim of this study is to evaluate the lymphatic and cardiovascular system in a cohort of adult women with TS to elucidate any defects, abnormalities or dysfunctions that may explain the myriad of complications related to TS.
Hypotheses:
- Both the lymphatic and cardiovascular system are affected in TS with alterations in both anatomy, flow, and function.
- Changes in the lymphatic system are more prevalent than previously assumed, affecting both central and peripheral lymphatic vessels.
- Changes in lymphatic transportation and development of cardiovascular malformations occur simultaneously in early fetal life, thus disease in either system may interplay with malfunctions in the other.
- The vascular structure in both lymph- and cardiovascular tissue is affected throughout the body and low-grade inflammation could be a possible factor in this pathogenesis in TS.
- Changes in the vascular structure affects flow through the systems resulting in increased stress point on vessel walls leading to a possible entry site for a dissection which can be detected through flow analyses.
- Genomic examination of multiple tissues will help in understanding the underlying genomic background for the congenital malformations seen in TS
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Turner Syndrome
Exclusion Criteria
- •pregnancy
- •contraindications for MRI
Arms & Interventions
Turner Syndrome
Women with karyotype verified Turner Syndrome n=100
Intervention: No intervention other than obtaining biopsies (Other)
Turner Syndrome
Women with karyotype verified Turner Syndrome n=100
Intervention: Indocyanine green (ICG) (Drug)
Female controls
Healthy, age-matched controls n=50
Intervention: No intervention other than obtaining biopsies (Other)
Female controls
Healthy, age-matched controls n=50
Intervention: Indocyanine green (ICG) (Drug)
Outcomes
Primary Outcomes
Detecting low-grade inflammation in Turner Syndrome preforming FDG-PET/CT-scans to locate low grade inflammation.
Time Frame: 3 years
Heat maps of the distribution of wall shear stress in the aorta
Time Frame: 3 years
Using 4D-flow analyses heat maps of the aorta will be made to illustrate the distribution of wall shear stress.
Grade dysfunction of clinical and subclinical lymphedema using Indocyanine Green Lymphography and Magnetic Resonance Lymphangiography.
Time Frame: 3 year
Lymphedema will be graded in a total score according to the International Society of Lymphology. The stages are: Stage 0: Subclinical lymphedema. • Stage 1: Early, reversible pitting edema. Stage 2: Irreversible lymphedema. Stage 3: End-stage lymphedema.
Secondary Outcomes
- Mapping DNA-methylations patterns in multiple tissues(3 years)
- MRI evaluation and description of vascular abnormalities in Turner Syndrome(3 years)
- Cardiac MRI to evaluate fibrosis of the myocardium(3 years)
- Cardiac MRI to evaluate function(3 years)
- Immunologic changes in Turner Syndrome(3 years)