Turner SyndromeTSCOR_VNCT06325618
Lymphedema, Low-grade Inflammation and the Vasculature in Turner Syndrome
An observational study of Turner Syndrome and Cardiovascular Diseases, run by University of Aarhus at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Turner Syndrome, Cardiovascular Diseases, Lymphedema
- What is being tested?
- Indocyanine green (ICG)
- How many people
- 150 participants
- Where
- 1 siteDenmark
- Study dates
- 8 Jan 2024to Aug 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Danish women.
Who may be able to join
- Turner Syndrome
Who cannot join
- pregnancy
- contraindications for MRI
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Aarhus University Hospital
Aarhus N, 8200
Line Balsby, MD, +4520461203, libals@clin.au.dk
Claus Gravholt, MD, Prof.
About this study
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.
Read the 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
Design:
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 lymphatic system will be examined using three different techniques to assess changes in both anatomy and function.
- The investigators will use Near infrared light to evaluate the lymphatic system and grade dysfunction and detect subclinical lymphedema. Indocyanine Green will be injected subcutaneously in the foot and hand and used to assess the flow 5-60 minutes after injection.
- A novel MRI technique to illustrate slow moving fluids, thus visualizing lymphatic fluid, will be used to display the contrast between fluids and tissue to view the thoracic duct and more peripheral lymphatic vessels and quantify their function, abnormalities and morphology.
- A DEXA scan will be performed to calculate and differentiate between subdermal fat and lymphatic drainage or edema.
To evaluate the cardiovascular system, the investigators will use MRI of the heart and aorta to asses both function and morphology to calculate, among others, mean cardiac output, stroke volume, ejection fraction and asses myocardial fibrosis. A novel technique is to use a PET-CT, as this has been associated with atherosclerosis, because it can visualize macrophage rich atherosclerotic plaques and thus detect otherwise undetectable low-grade inflammation and disease in the cardiovascular system which may contribute to the development of cardiovascular complications.
The investigators will also evaluate the flow in the aorta using 4D-flow measurements based on customized MRI protocols to evaluate stress on the aortic wall and analyze the risk of aortic wall rupture and dissection. The potential of this analysis is the possibility to identify patients at high risk and need for medical or surgical intervention at an early stage and thus prevent or minimize this acute life-threatening complication to TS.
Genomic studies: Samples will be taken from multiple tissues (Blood, fat, muscle, skin, buccal swaps, urine) and DNA and RNA will be isolated using standard methodology.
- Conditions
- Turner Syndrome, Cardiovascular Diseases, Lymphedema, Inflammation
- Being tested
- No intervention other than obtaining biopsies, Indocyanine green (ICG)
- Medical subject headings
- Turner Syndrome, Cardiovascular Diseases, Lymphedema, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No intervention other than obtaining biopsiesOther
Skin, fat, and muscle biopsies will be obtained
Indocyanine green (ICG)Drug
Indocyanine green will be injected to evaluate the lymphatic system.
| Study group | Role | What they receive |
|---|---|---|
| Turner Syndrome | Women with karyotype verified Turner Syndrome n=100 Receives: Other: No intervention other than obtaining biopsies; Drug: Indocyanine green (ICG) | |
| Female controls | Healthy, age-matched controls n=50 Receives: Other: No intervention other than obtaining biopsies; Drug: Indocyanine green (ICG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade dysfunction of clinical and subclinical lymphedema using Indocyanine Green Lymphography and Magnetic Resonance Lymphangiography.
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.
Measured: 3 year
Detecting low-grade inflammation in Turner Syndrome preforming FDG-PET/CT-scans to locate low grade inflammation.
Measured: 3 years
Heat maps of the distribution of wall shear stress in the aorta
Using 4D-flow analyses heat maps of the aorta will be made to illustrate the distribution of wall shear stress.
Measured: 3 years
Secondary outcomes (5)
MRI evaluation and description of vascular abnormalities in Turner Syndrome
Aortic dimensions
Measured: 3 years
Cardiac MRI to evaluate function
Diastolic and systolic function of the left ventricle
Measured: 3 years
Cardiac MRI to evaluate fibrosis of the myocardium
Estimation of myocardial fibrosis
Measured: 3 years
Mapping DNA-methylations patterns in multiple tissues
Mapping DNA-methylation patterns in muscle, skin, fat, blood and urine
Measured: 3 years
Immunologic changes in Turner Syndrome
Measuring blood concentrations of neutrophiles and lymphocytes, to asses neutrophil-to-lymphocyte ratio (NLR).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start8 Jan 2024
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Turner SyndromeStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06325618
- Sponsor's protocol ID
- 1-10-72-138-23
- Acronym
- TSCOR_V
- Status last verified
- Jan 2024
- First submitted
- 20 Feb 2024
- Last updated
- 22 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mortensen KH, Andersen NH, Gravholt CH. Cardiovascular phenotype in Turner syndrome--integrating cardiology, genetics, and endocrinology. Endocr Rev. 2012 Oct;33(5):677-714. doi: 10.1210/er.2011-1059. Epub 2012 Jun 15.
PubMed 22707402Hjerrild BE, Mortensen KH, Sorensen KE, Pedersen EM, Andersen NH, Lundorf E, Hansen KW, Horlyck A, Hager A, Christiansen JS, Gravholt CH. Thoracic aortopathy in Turner syndrome and the influence of bicuspid aortic valves and blood pressure: a CMR study. J Cardiovasc Magn Reson. 2010 Mar 11;12(1):12. doi: 10.1186/1532-429X-12-12.
PubMed 20222980Executive Committee. The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of Lymphology. Lymphology. 2016 Dec;49(4):170-84.
PubMed 29908550Yu DX, Ma XX, Zhang XM, Wang Q, Li CF. Morphological features and clinical feasibility of thoracic duct: detection with nonenhanced magnetic resonance imaging at 3.0 T. J Magn Reson Imaging. 2010 Jul;32(1):94-100. doi: 10.1002/jmri.22128.
PubMed 20578016Unno N, Nishiyama M, Suzuki M, Yamamoto N, Inuzuka K, Sagara D, Tanaka H, Konno H. Quantitative lymph imaging for assessment of lymph function using indocyanine green fluorescence lymphography. Eur J Vasc Endovasc Surg. 2008 Aug;36(2):230-236. doi: 10.1016/j.ejvs.2008.04.013. Epub 2008 Jun 4.
PubMed 18534875Mohanakumar S, Telinius N, Kelly B, Lauridsen H, Boedtkjer D, Pedersen M, de Leval M, Hjortdal V. Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation. Circ Cardiovasc Imaging. 2019 Apr;12(4):e008074. doi: 10.1161/CIRCIMAGING.118.008074.
PubMed 30943769
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lymphedema, Low-grade Inflammation and the Vasculature in Turner Syndrome
- ClinicalTrials.gov ID
- NCT06325618
- Acronym / sponsor ID
- TSCOR_V / 1-10-72-138-23
- Conditions
- Turner Syndrome, Cardiovascular Diseases, Lymphedema, Inflammation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital
- Study start
- 8 Jan 2024 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 22 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Design:
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 lymphatic system will be examined using three different techniques to assess changes in both anatomy and function.
- The investigators will use Near infrared light to evaluate the lymphatic system and grade dysfunction and detect subclinical lymphedema. Indocyanine Green will be injected subcutaneously in the foot and hand and used to assess the flow 5-60 minutes after injection.
- A novel MRI technique to illustrate slow moving fluids, thus visualizing lymphatic fluid, will be used to display the contrast between fluids and tissue to view the thoracic duct and more peripheral lymphatic vessels and quantify their function, abnormalities and morphology.
- A DEXA scan will be performed to calculate and differentiate between subdermal fat and lymphatic drainage or edema.
To evaluate the cardiovascular system, the investigators will use MRI of the heart and aorta to asses both function and morphology to calculate, among others, mean cardiac output, stroke volume, ejection fraction and asses myocardial fibrosis. A novel technique is to use a PET-CT, as this has been associated with atherosclerosis, because it can visualize macrophage rich atherosclerotic plaques and thus detect otherwise undetectable low-grade inflammation and disease in the cardiovascular system which may contribute to the development of cardiovascular complications.
The investigators will also evaluate the flow in the aorta using 4D-flow measurements based on customized MRI protocols to evaluate stress on the aortic wall and analyze the risk of aortic wall rupture and dissection. The potential of this analysis is the possibility to identify patients at high risk and need for medical or surgical intervention at an early stage and thus prevent or minimize this acute life-threatening complication to TS.
Genomic studies: Samples will be taken from multiple tissues (Blood, fat, muscle, skin, buccal swaps, urine) and DNA and RNA will be isolated using standard methodology.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Turner Syndrome | – | Other: No intervention other than obtaining biopsies, Drug: Indocyanine green (ICG)Women with karyotype verified Turner Syndrome n=100 |
| Female controls | – | Other: No intervention other than obtaining biopsies, Drug: Indocyanine green (ICG)Healthy, age-matched controls n=50 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Danish women.
Key inclusion criteria (1 listed)
- Turner Syndrome
Key exclusion criteria (2 listed)
- pregnancy
- contraindications for MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No intervention other than obtaining biopsiesSkin, fat, and muscle biopsies will be obtained | Other | Female controls, Turner Syndrome |
| Indocyanine green (ICG)Indocyanine green will be injected to evaluate the lymphatic system. | Drug | Female controls, Turner Syndrome |
Primary outcome
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.
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.
5 secondary outcomes
MRI evaluation and description of vascular abnormalities in Turner Syndrome
Time frame: 3 years
Cardiac MRI to evaluate function
Time frame: 3 years
Cardiac MRI to evaluate fibrosis of the myocardium
Time frame: 3 years
Mapping DNA-methylations patterns in multiple tissues
Time frame: 3 years
Immunologic changes in Turner Syndrome
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
- Background: PubMed 22707402Mortensen KH, Andersen NH, Gravholt CH. Cardiovascular phenotype in Turner syndrome--integrating cardiology, genetics, and endocrinology. Endocr Rev. 2012 Oct;33(5):677-714. doi: 10.1210/er.2011-1059. Epub 2012 Jun 15.
- Background: PubMed 20222980Hjerrild BE, Mortensen KH, Sorensen KE, Pedersen EM, Andersen NH, Lundorf E, Hansen KW, Horlyck A, Hager A, Christiansen JS, Gravholt CH. Thoracic aortopathy in Turner syndrome and the influence of bicuspid aortic valves and blood pressure: a CMR study. J Cardiovasc Magn Reson. 2010 Mar 11;12(1):12. doi: 10.1186/1532-429X-12-12.
- Background: PubMed 29908550Executive Committee. The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of Lymphology. Lymphology. 2016 Dec;49(4):170-84.
- Background: PubMed 20578016Yu DX, Ma XX, Zhang XM, Wang Q, Li CF. Morphological features and clinical feasibility of thoracic duct: detection with nonenhanced magnetic resonance imaging at 3.0 T. J Magn Reson Imaging. 2010 Jul;32(1):94-100. doi: 10.1002/jmri.22128.
- Background: PubMed 18534875Unno N, Nishiyama M, Suzuki M, Yamamoto N, Inuzuka K, Sagara D, Tanaka H, Konno H. Quantitative lymph imaging for assessment of lymph function using indocyanine green fluorescence lymphography. Eur J Vasc Endovasc Surg. 2008 Aug;36(2):230-236. doi: 10.1016/j.ejvs.2008.04.013. Epub 2008 Jun 4.
- Background: PubMed 30943769Mohanakumar S, Telinius N, Kelly B, Lauridsen H, Boedtkjer D, Pedersen M, de Leval M, Hjortdal V. Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation. Circ Cardiovasc Imaging. 2019 Apr;12(4):e008074. doi: 10.1161/CIRCIMAGING.118.008074.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Turner Syndrome and Cardiovascular Diseases, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Line Balsby, MD (+4520461203, libals@clin.au.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Grade dysfunction of clinical and subclinical lymphedema using Indocyanine Green Lymphography and Magnetic Resonance Lymphangiography. (time frame: 3 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06325618, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.