Gorham DiseaseNCT02744027
Imaging of Lymphatic Anomalies
A study testing Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL), Heavy Weighted T2 Imaging (T2W) and Lymph Node Access in people with Gorham Disease and Lymphatic Diseases, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
Lymphatic Anomalies (LA) is characterized by proliferation of lymphatic tissue causing deterioration of pulmonary function. Understanding changes in lymphatic anatomy in these patients is hindered by the difficulty of imaging the lymphatic system. Read more about this study
- Who is it for?
- Ages 2 to 80 years
- Conditions the study is for
- Gorham Disease, Lymphatic Diseases, Lymphangiomatosis
- What is being tested?
- Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL), Heavy Weighted T2 Imaging (T2W) and Lymph Node Access
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Dec 2017
- 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 2 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects diagnosed with Lymphatic Anomalies (GLA, KL, Gorham disease) with radiological and or pathological confirmation of lung involvement will be considered for the study.
- Girls > 11 y.o. with a negative urine pregnancy test and contraception use.
- Registration in the International Lymphangiomatosis and Gorham's Disease Alliance (LGDA) Patient Registry or referral by a physician.
Who cannot join
- Subjects with contraindications to contrast enhanced MRI: allergy to gadolinium imaging agents, impaired renal function (GFR<30) and presence of paramagnetic objects.
- Claustrophobia or contraindications to sedation/anesthesia
- Uncorrectable coagulopathy (bleeding disorders).
- Pregnant or lactating females.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Dynamic Contrast Enhanced MR Lymphangiogram Imaging of Lymphatic Anomalies (LA)
Lymphatic Anomalies (LA) is characterized by proliferation of lymphatic tissue causing deterioration of pulmonary function. Understanding changes in lymphatic anatomy in these patients is hindered by the difficulty of imaging the lymphatic system. Dynamic Contrast Enhanced MR Lymphangiogram (DCMRL) may be useful in investigating pathological changes in the lymphatic system.
Read the detailed description
Lymphatic anomalies (LA) are a spectrum of rare diseases classified into lymphatic tumors and malformations. Complicated LA cases in the past have been called lymphangiomatosis because of varied disseminated involvement including soft tissue and viscera such as the spleen, liver and bone. Pleural effusions and pericardial effusions are often associated with these lesions. These are now classified into different phenotypes such as Generalized Lymphatic Anomaly (GLA), Gorham's Stout Disease (GSD) and Kaposiform Lymphangiomatosis (KLA). These complicated phenotypes can cause massive osteolysis causing a morbidity and mortality from infection or paralysis or worsening pulmonary function and effusions (GSD, GLA, KLA).
The major cause of mortality and morbidity in these patients is the deterioration of pulmonary function by chronic chylous effusions and progressive interstitial lung disease. Unfortunately, little is known about biomarkers, risk stratification or the pathophysiology of this progression. The understanding of changes in patients' lymphatic anatomy with LA is hindered by the difficulty of imaging the lymphatic system. Dynamic Contrast Enhanced MR Lymphangiogram (DCMRL) is a technique that has recently been developed, allowing dynamic MR imaging of the lymphatic system by injecting gadolinium contrast agent in the groin lymph nodes.
This technique has been previously used to identify pathological lymphatic perfusion of the lung parenchyma in patients with plastic bronchitis and neonatal chylothorax. Based on these imaging findings, a treatment algorithm has been designed and used to successfully treat the majority of those patients with these conditions.
- Conditions
- Gorham Disease, Lymphatic Diseases, Lymphangiomatosis
- Being tested
- Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL), Heavy Weighted T2 Imaging (T2W), Lymph Node Access
- Keywords
- Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, Dynamic Contrast Enhanced Magnetic Resonance Lymphangiogram, Magnetic Resonance Imaging
- Medical subject headings
- Osteolysis, Essential, Lymphatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL)Other
Following completion of the T2 lymphatic mapping, contrast agent administered will be calculated based on weight. Investigators will use dosage of 0.1cc/kg of contrast which will be injected by hand simultaneously into each lymphatic node (LN) at a rate of 0.5-1 cc per min. One minute after the injection, scanning will be initiated using high spatial and temporal resolution magnetic resonance angiography (syngo time-resolved angiography with stochastic trajectories [TWIST]) sequence. The sequence parameters will be adjusted with a time delay such that a complete volume will be acquired approximately every 20-60 seconds. This will be followed by additional scans with a high-resolution navigator gated 3-dimensional flash inversion recovery (IR) sequence. In all subjects the scan area covered the neck, chest, and abdomen as caudal as feasible.
Heavy Weighted T2 Imaging (T2W)Other
Magnetic Resonance imaging (MRI) will be performed and T2W MRI lymphatic mapping will be performed using a respiratory navigated and cardiac gated 3 dimensional turbo spin echo sequence with pre-set parameters. Scan time varies from 2-5 min depending upon the size of the subject.
Lymph Node AccessOther
The procedure will be performed under sedation and anesthesia if participants are aged 16 or under. The procedure will be performed with local anesthesia for participants aged over 16 years old.
Using ultrasound guidance two inguinal lymph nodes (one each side) will be directly accessed with 25-gauge spinal needles attached to a short connector tubing. A shallow angle for puncture will be used to create a long subcutaneous tract to assist in stabilizing the needle. A small amount of an oil-based contrast or water soluble contrast will be injected under fluoroscopy guidance to confirm the correct position of the needles inside the lymph nodes. After stabilizing the needle, the subjects will be transferred into the MRI suite.
| Study group | Role | What they receive |
|---|---|---|
| Dynamic Contrast Enhanced Magnetic Contrast Imaging | Other | Dynamic Contrast Enhanced Magnetic Resonance (MR) Lymphangiogram and heavy T2 Magnetic Resonance imaging data will be evaluated for abnormal lymphatic perfusion of the lung parenchyma. Abdominal and thoracic lymphatic malformations will be characterized by location, number, size, relationship to other organs and perfusion patterns in order to create a basis of imaging classification of lymphatic abnormalities (LA). Subjects will undergo both Dynamic Contrast Enhanced Magnetic Resonance Lymphangiogram (DCMRL) and Heavy Weighted T2 Imaging. Receives: Other: Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL); Other: Heavy Weighted T2 Imaging (T2W); Other: Lymph Node Access |
What is being measured
The primary outcome is the main question the study is designed to answer.
Describe lymphatic anatomy of participants with lymphatic anomalies (LA)
The primary endpoint will be the description of lymphatic anatomy assessing if participants have a single or branched Thoracic Duct.
Measured: 2 Days
Secondary outcomes (2)
Development of a classification system for lymphatic flow
Development of a classification system based on retrograde or anterograde flow of lymphatic fluid.
Measured: 2 days
Description of Lymphatic malformations in participants with lymphatic anomalies
Assessing if lymphatic malformation are present or absent in participants with lymphatic anomalies.
Measured: 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2016 (estimated)
- Study startApr 2016
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gorham DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania
- Responsible party
- Sponsor
- Investigators
- Yoav Dori, MD, PhD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02744027
- Sponsor's protocol ID
- 15-012331
- Status last verified
- Mar 2018
- First submitted
- 11 Apr 2016
- Last updated
- 21 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Itkin M, Rabinowitz DA, Nadolski G, Stafler P, Mascarenhas L, Adams D. Abnormal Pulmonary Lymphatic Flow in Patients With Lymphatic Anomalies and Respiratory Compromise. Chest. 2020 Aug;158(2):681-691. doi: 10.1016/j.chest.2020.02.058. Epub 2020 Mar 24.
PubMed 32220591
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamic Contrast Enhanced MR Lymphangiogram Imaging of Lymphatic Anomalies (LA)
- ClinicalTrials.gov ID
- NCT02744027
- Acronym / sponsor ID
- 15-012331
- Conditions
- Gorham Disease, Lymphatic Diseases, Lymphangiomatosis
- Keywords
- Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, Dynamic Contrast Enhanced Magnetic Resonance Lymphangiogram, Magnetic Resonance Imaging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- University of Pennsylvania
- Study start
- Apr 2016
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 20 Apr 2016 (estimated)
- 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.
Lymphatic Anomalies (LA) is characterized by proliferation of lymphatic tissue causing deterioration of pulmonary function. Understanding changes in lymphatic anatomy in these patients is hindered by the difficulty of imaging the lymphatic system. Dynamic Contrast Enhanced MR Lymphangiogram (DCMRL) may be useful in investigating pathological changes in the lymphatic system.
Detailed description
Lymphatic anomalies (LA) are a spectrum of rare diseases classified into lymphatic tumors and malformations. Complicated LA cases in the past have been called lymphangiomatosis because of varied disseminated involvement including soft tissue and viscera such as the spleen, liver and bone. Pleural effusions and pericardial effusions are often associated with these lesions. These are now classified into different phenotypes such as Generalized Lymphatic Anomaly (GLA), Gorham's Stout Disease (GSD) and Kaposiform Lymphangiomatosis (KLA). These complicated phenotypes can cause massive osteolysis causing a morbidity and mortality from infection or paralysis or worsening pulmonary function and effusions (GSD, GLA, KLA).
The major cause of mortality and morbidity in these patients is the deterioration of pulmonary function by chronic chylous effusions and progressive interstitial lung disease. Unfortunately, little is known about biomarkers, risk stratification or the pathophysiology of this progression. The understanding of changes in patients' lymphatic anatomy with LA is hindered by the difficulty of imaging the lymphatic system. Dynamic Contrast Enhanced MR Lymphangiogram (DCMRL) is a technique that has recently been developed, allowing dynamic MR imaging of the lymphatic system by injecting gadolinium contrast agent in the groin lymph nodes.
This technique has been previously used to identify pathological lymphatic perfusion of the lung parenchyma in patients with plastic bronchitis and neonatal chylothorax. Based on these imaging findings, a treatment algorithm has been designed and used to successfully treat the majority of those patients with these conditions.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dynamic Contrast Enhanced Magnetic Contrast Imaging | Other | Other: Dynamic Contrast Enhanced Magnetic Resonance Lymphangiography (DCMRL), Other: Heavy Weighted T2 Imaging (T2W), Other: Lymph Node AccessDynamic Contrast Enhanced Magnetic Resonance (MR) Lymphangiogram and heavy T2 Magnetic Resonance imaging data will be evaluated for abnormal lymphatic perfusion of the lung parenchyma. Abdominal and thoracic lymphatic malformations will be characterized by location, number, size, relationship to other organs and perfusion patterns in order to create a basis of imaging classification of lymphatic abnormalities (LA). Subjects will undergo both Dynamic Contrast Enhanced Magnetic Resonance Lymphangiogram (DCMRL) and Heavy Weighted T2 Imaging. |
Who may qualify
- Ages
- 2 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects diagnosed with Lymphatic Anomalies (GLA, KL, Gorham disease) with radiological and or pathological confirmation of lung involvement will be considered for the study.
- Girls > 11 y.o. with a negative urine pregnancy test and contraception use.
- Registration in the International Lymphangiomatosis and Gorham's Disease Alliance (LGDA) Patient Registry or referral by a physician.
Key exclusion criteria (4 listed)
- Subjects with contraindications to contrast enhanced MRI: allergy to gadolinium imaging agents, impaired renal function (GFR<30) and presence of paramagnetic objects.
- Claustrophobia or contraindications to sedation/anesthesia
- Uncorrectable coagulopathy (bleeding disorders).
- Pregnant or lactating females.
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 Magnetic Resonance Lymphangiography (DCMRL)Following completion of the T2 lymphatic mapping, contrast agent administered will be calculated based on weight. Investigators will use dosage of 0.1cc/kg of contrast which will be injected by hand simultaneously into each lymphatic node (LN) at a rate of 0.5-1 cc per min. One minute after the injection, scanning will be initiated using high spatial and temporal resolution magnetic resonance angiography (syngo time-resolved angiography with stochastic trajectories [TWIST]) sequence. The sequence parameters will be adjusted with a time delay such that a complete volume will be acquired approximately every 20-60 seconds. This will be followed by additional scans with a high-resolution navigator gated 3-dimensional flash inversion recovery (IR) sequence. In all subjects the scan area covered the neck, chest, and abdomen as caudal as feasible. | Other | Dynamic Contrast Enhanced Magnetic Contrast Imaging |
| Heavy Weighted T2 Imaging (T2W)Magnetic Resonance imaging (MRI) will be performed and T2W MRI lymphatic mapping will be performed using a respiratory navigated and cardiac gated 3 dimensional turbo spin echo sequence with pre-set parameters. Scan time varies from 2-5 min depending upon the size of the subject. | Other | Dynamic Contrast Enhanced Magnetic Contrast Imaging |
| Lymph Node AccessThe procedure will be performed under sedation and anesthesia if participants are aged 16 or under. The procedure will be performed with local anesthesia for participants aged over 16 years old. Using ultrasound guidance two inguinal lymph nodes (one each side) will be directly accessed with 25-gauge spinal needles attached to a short connector tubing. A shallow angle for puncture will be used to create a long subcutaneous tract to assist in stabilizing the needle. A small amount of an oil-based contrast or water soluble contrast will be injected under fluoroscopy guidance to confirm the correct position of the needles inside the lymph nodes. After stabilizing the needle, the subjects will be transferred into the MRI suite. | Other | Dynamic Contrast Enhanced Magnetic Contrast Imaging |
Primary outcome
Describe lymphatic anatomy of participants with lymphatic anomalies (LA)
Time frame: 2 Days
The primary endpoint will be the description of lymphatic anatomy assessing if participants have a single or branched Thoracic Duct.
2 secondary outcomes
Development of a classification system for lymphatic flow
Time frame: 2 days
Description of Lymphatic malformations in participants with lymphatic anomalies
Time frame: 2 days
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 21 Mar 2018.
- Derived from this study: PubMed 32220591Itkin M, Rabinowitz DA, Nadolski G, Stafler P, Mascarenhas L, Adams D. Abnormal Pulmonary Lymphatic Flow in Patients With Lymphatic Anomalies and Respiratory Compromise. Chest. 2020 Aug;158(2):681-691. doi: 10.1016/j.chest.2020.02.058. Epub 2020 Mar 24.
- Individual participant dataSharing planned: No
Related trials for Gorham Disease
RecruitingObservational study
A Prospective Natural History Study of Lymphatic Anomalies
Lymphatic Diseases, Lymphatic Abnormalities
RecruitingObservational study
Lymphatic Anomalies Registry for the Assessment of Outcome Data
Lymphatic Malformation, Generalized Lymphatic Anomaly (GLA)
RecruitingObservational study
Identification of Biomarkers for Patients with Vascular Anomalies
Vascular Anomaly, Generalized Lymphatic Anomaly
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.
Yoav Dori, MD, PhD principal investigator
Children's Hospital of Philadelphia
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 Magnetic Resonance Lymphangiography (DCMRL), Heavy Weighted T2 Imaging (T2W) and Lymph Node Access in people with Gorham Disease and Lymphatic Diseases, run by Children's Hospital of Philadelphia at 1 site in United States.
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 3 inclusion and 4 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 21 Mar 2018. 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 United States. 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?
Describe lymphatic anatomy of participants with lymphatic anomalies (LA) (time frame: 2 Days). 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 NCT02744027, which also lists 1 linked publication.
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 21 Mar 2018.