Lymphatic System Disorders CongenitalLENSNCT06267807
Lymphatic Phenotype in Noonan Syndrome Spectrum Disorders
A study testing Dynamic contrast-enhanced lymphangiography in people with Lymphatic System Disorders Congenital and Lymphatic Diseases, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
To get a better insight into the central conducting lymphatic system in adult volunteers with Noonan Syndrome (NS) without clinical symptoms or signs of lymphatic disease compared to NS and CardioFacioCutaan syndrome patients with severe lymphatic disease Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphatic System Disorders Congenital, Lymphatic Diseases, Noonan Syndrome
- What is being tested?
- Dynamic contrast-enhanced lymphangiography
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteNetherlands
- Study dates
- 27 Mar 2024to 1 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Noonan Syndrome confirmed by genetic test with a class 4 or 5 pathogenic variant according to ClinVar
- 18 years and older (no restriction for sex)
- Willing and able to have MR lymphangiography scanning in the Radboudumc
- Oral and written informed consent
- None of the exclusion criteria
Who cannot join
- unsuitable for MRI (e.g. metallic objects in the body, severe claustrophobia)
- A history of symptoms related to lymphatic disease
- pregnancy
- renal insufficiency
- liver cirrhosis
- History of surgery related to cardiovascular disease with hemodynamic consequence
- Other genetic diseases
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Lymphatic Phenotype in Patients With Noonan Syndrome Without a Clinical History of Lymphatic Disease
To get a better insight into the central conducting lymphatic system in adult volunteers with Noonan Syndrome (NS) without clinical symptoms or signs of lymphatic disease compared to NS and CardioFacioCutaan syndrome patients with severe lymphatic disease
Read the detailed description
Rationale: Noonan Syndrome Spectrum Disorders (NSSDs) are caused by pathogenic variants in genes of the Ras/MAPK signaling pathway, and belong to the RASopathy.
Lymphatic disease occur in 36% of patients with Noonan Syndrome (NS) during their lifetime, with different symptoms, severity, and onset. However, it is unknown how many patients with RASopathy are exactly impaired with lymph flow disorders, since many of these patients have unrecognized symptoms and go undiagnosed. For example, patients diagnosed with primary lymphedema (which implies being without known etiologic cause) may have an anatomic or functional abnormality of the central conducting lymph system that is not diagnosed as the causative lymph flow problem. With the diagnosis being based on the symptoms and not on the underlying pathophysiological mechanism, therapy will focus on diminishing symptoms and not on healing the pathophysiological cause. To eventually improve therapeutic intervention, a better understanding of the pathophysiology is necessary, and may be found by studying the central conducting lymphatic system of patients with NS and lymphatic disease, and adult volunteers with Noonan Syndrome without lymphatic disease. Objective: To get a better insight into the central conducting lymphatic system in adult volunteers with Noonan Syndrome (NS) without clinical symptoms or signs of lymphatic disease compared to NS and CardioFacioCutaan syndrome patients with severe lymphatic disease and healthy volunteers. (ongoing study: (Lymphomics; improving the understanding the anatomy of the lymphatic system and the direction and velocity of lymph flow; approved by the Medical Ethics Committee at Radboud University Medical Center Nijmegen file number 2021-7514) Study design: A single center, prospective collection of data Study population: Adult volunteers with Noonan Syndrome without (a history of) complaints or signs of lymphatic disease. Intervention: Three questionnaires (general health, lymphatic abnormalities and general MRI safety) will be taken prior to the dynamic MR lymphangiography. In addition to standard physical examination and electronic patient file screening, for inclusion and exclusion purposes. Subsequently, the MR lymphangiography will be performed. After 24 hours, the subject will be called for a follow-up by phone. Main study parameters/endpoints: the anatomy of the central lymph vessels, the velocity and direction of lymph flow, which can be compared with reference values. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation in this study places subjects at minimal risk. Subjects will undergo placement of a small needle in an inguinal lymph node on both sides, with very little risk of bleeding and/or infection, as with other minimal invasive procedures. The dynamic MR lymphangiography will take approximately two hours
- Conditions
- Lymphatic System Disorders Congenital, Lymphatic Diseases, Noonan Syndrome, Lymphatic Disease
- Being tested
- Dynamic contrast-enhanced lymphangiography
- Medical subject headings
- Lymphatic Diseases, Noonan Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dynamic contrast-enhanced lymphangiographyDiagnostic test
Also called MR lymphangiography
The subject is placed supine on a detachable MR imaging table, outside the scanning room. Both inguinal regions are prepared under sterile conditions. Using Ultrasound guidance, the thoracic duct outlet at the left venous angle is identified. Under US guidance, a small 25 gauge needle is placed at the corticomedullar junction of an inguinal lymph node on each side. The needle position is confirmed and checked that there is no extravasation at saline injection under US visualization. The subject is then transferred to the MR imaging machine. First, pre-contrast imaging is performed, this takes around 20 minutes.
| Study group | Role | What they receive |
|---|---|---|
| MR lymphangiography contrast injection | Other | GBCM will be administered. Any routinely used macrocyclic GBCM can be used for MR lymphangiography, we generally use Dotarem® (Gadoteric acid- gadoterate meglumine). The dose used is the same standard dose of 0.1 mmol/kg of body weight used for routine intravenous injection. The guidelines and precautions used for intravenous injection of GBCM, should be followed for MR lymphangiography.
Subsequently, post-contrast imaging is performed (again, this will take around 20 minutes) Receives: Diagnostic Test: Dynamic contrast-enhanced lymphangiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central lymphatic system anatomy and flow descriptive parameters.
Categorical assessment of the anatomy and lymphatic flow in the central lymphatic system. Including the presence or absence of the central lymphatic vessels, edema and fluid collections.
Measured: Through study completion, an average of 1 year.
Diameter Thoracic duct
Measurements consist of the maximal diameter of the thoracic duct, the diameter at the level of the diaphragm, and the width and length of the cisterna chyli.
Measured: Through study completion, an average of 1 year.
Lymph flow velocity
Lymph flow velocity will be determined on the dynamic MR lymphangiography by measuring the distance of contrast movement covered over time in cm/min.
Measured: Through study completion, an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start27 Mar 2024
- Primary completion1 Apr 2025
- Study completion1 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphatic System Disorders CongenitalStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06267807
- Sponsor's protocol ID
- 114369
- Other IDs
- NL84520.091.23
- Acronym
- LENS
- Status last verified
- Apr 2024
- First submitted
- 18 Jan 2024
- Last updated
- 25 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lymphatic Phenotype in Patients With Noonan Syndrome Without a Clinical History of Lymphatic Disease
- ClinicalTrials.gov ID
- NCT06267807
- Acronym / sponsor ID
- LENS / 114369
- Conditions
- Lymphatic System Disorders Congenital, Lymphatic Diseases, Noonan Syndrome, Lymphatic Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 27 Mar 2024 (actual)
- Primary completion
- 1 Apr 2025 (actual)
- Study completion
- 1 Apr 2025 (actual)
- First posted
- 20 Feb 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.
To get a better insight into the central conducting lymphatic system in adult volunteers with Noonan Syndrome (NS) without clinical symptoms or signs of lymphatic disease compared to NS and CardioFacioCutaan syndrome patients with severe lymphatic disease
Detailed description
Rationale: Noonan Syndrome Spectrum Disorders (NSSDs) are caused by pathogenic variants in genes of the Ras/MAPK signaling pathway, and belong to the RASopathy.
Lymphatic disease occur in 36% of patients with Noonan Syndrome (NS) during their lifetime, with different symptoms, severity, and onset. However, it is unknown how many patients with RASopathy are exactly impaired with lymph flow disorders, since many of these patients have unrecognized symptoms and go undiagnosed. For example, patients diagnosed with primary lymphedema (which implies being without known etiologic cause) may have an anatomic or functional abnormality of the central conducting lymph system that is not diagnosed as the causative lymph flow problem. With the diagnosis being based on the symptoms and not on the underlying pathophysiological mechanism, therapy will focus on diminishing symptoms and not on healing the pathophysiological cause. To eventually improve therapeutic intervention, a better understanding of the pathophysiology is necessary, and may be found by studying the central conducting lymphatic system of patients with NS and lymphatic disease, and adult volunteers with Noonan Syndrome without lymphatic disease. Objective: To get a better insight into the central conducting lymphatic system in adult volunteers with Noonan Syndrome (NS) without clinical symptoms or signs of lymphatic disease compared to NS and CardioFacioCutaan syndrome patients with severe lymphatic disease and healthy volunteers. (ongoing study: (Lymphomics; improving the understanding the anatomy of the lymphatic system and the direction and velocity of lymph flow; approved by the Medical Ethics Committee at Radboud University Medical Center Nijmegen file number 2021-7514) Study design: A single center, prospective collection of data Study population: Adult volunteers with Noonan Syndrome without (a history of) complaints or signs of lymphatic disease. Intervention: Three questionnaires (general health, lymphatic abnormalities and general MRI safety) will be taken prior to the dynamic MR lymphangiography. In addition to standard physical examination and electronic patient file screening, for inclusion and exclusion purposes. Subsequently, the MR lymphangiography will be performed. After 24 hours, the subject will be called for a follow-up by phone. Main study parameters/endpoints: the anatomy of the central lymph vessels, the velocity and direction of lymph flow, which can be compared with reference values. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation in this study places subjects at minimal risk. Subjects will undergo placement of a small needle in an inguinal lymph node on both sides, with very little risk of bleeding and/or infection, as with other minimal invasive procedures. The dynamic MR lymphangiography will take approximately two hours
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MR lymphangiography contrast injection | Other | Diagnostic Test: Dynamic contrast-enhanced lymphangiographyGBCM will be administered. Any routinely used macrocyclic GBCM can be used for MR lymphangiography, we generally use Dotarem® (Gadoteric acid- gadoterate meglumine). The dose used is the same standard dose of 0.1 mmol/kg of body weight used for routine intravenous injection. The guidelines and precautions used for intravenous injection of GBCM, should be followed for MR lymphangiography. Subsequently, post-contrast imaging is performed (again, this will take around 20 minutes) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Noonan Syndrome confirmed by genetic test with a class 4 or 5 pathogenic variant according to ClinVar
- 18 years and older (no restriction for sex)
- Willing and able to have MR lymphangiography scanning in the Radboudumc
- Oral and written informed consent
- None of the exclusion criteria
Key exclusion criteria (7 listed)
- unsuitable for MRI (e.g. metallic objects in the body, severe claustrophobia)
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 |
|---|---|---|
| Dynamic contrast-enhanced lymphangiographyAlso: MR lymphangiographyThe subject is placed supine on a detachable MR imaging table, outside the scanning room. Both inguinal regions are prepared under sterile conditions. Using Ultrasound guidance, the thoracic duct outlet at the left venous angle is identified. Under US guidance, a small 25 gauge needle is placed at the corticomedullar junction of an inguinal lymph node on each side. The needle position is confirmed and checked that there is no extravasation at saline injection under US visualization. The subject is then transferred to the MR imaging machine. First, pre-contrast imaging is performed, this takes around 20 minutes. | Diagnostic test | MR lymphangiography contrast injection |
Primary outcome
Central lymphatic system anatomy and flow descriptive parameters.
Time frame: Through study completion, an average of 1 year.
Categorical assessment of the anatomy and lymphatic flow in the central lymphatic system. Including the presence or absence of the central lymphatic vessels, edema and fluid collections.
Diameter Thoracic duct
Time frame: Through study completion, an average of 1 year.
Measurements consist of the maximal diameter of the thoracic duct, the diameter at the level of the diaphragm, and the width and length of the cisterna chyli.
Lymph flow velocity
Time frame: Through study completion, an average of 1 year.
Lymph flow velocity will be determined on the dynamic MR lymphangiography by measuring the distance of contrast movement covered over time in cm/min.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2025.
- Individual participant dataSharing planned: No. No plan
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dynamic contrast-enhanced lymphangiography in people with Lymphatic System Disorders Congenital and Lymphatic Diseases, run by Radboud University Medical Center at 1 site in Netherlands.
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 5 inclusion and 7 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: finished, as of the sponsor's last update on 25 Apr 2025. 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 Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central lymphatic system anatomy and flow descriptive parameters. (time frame: Through study completion, an average of 1 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?
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 25 Apr 2025.