- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02977637
MRA With Feraheme in HHT
The Use of Ferumoxytol (Feraheme) for Whole Body Magnetic Resonance Angiography in Hereditary Hemorrhagic Telangiectasia
Magnetic resonance (MR) imaging is performed with contrast agents to highlight the blood vessels and allow interpretation and diagnosis of blood vessel abnormalities. HHT (Hereditary Hemorrhagic Telangiectasia) is a disease of blood vessels, and can suffer fatal bleeding if abnormal blood vessels are not detected and treated early. Patients with HHT also require many imaging studies through their lifetimes for surveillance of blood vessels. Many HHT patients also have co-existing iron deficiency anemia from bleeding in their nose and gastrointestinal tract, and receive daily iron therapy.
Ferumoxytol is an alternative MR contrast agent, which is FDA (Food and Drug Administration) approved for the treatment of iron deficiency anemia. In addition, it is not associated with the risks to the kidneys of the other agents. The use of ferumoxytol for MR imaging may benefit the patients who do not currently receive imaging due to the contraindications of the conventional contrast agents. It avoids the use of ionizing radiation. Also, the conventional contrast agents are associated with risks. Iodinated contrast in CT is associated with significant risks of kidney damage. Another imaging technique, MR, uses gadolinium based contrast agents. Gadolinium, if used in patients with pre existing kidney dysfunction (defined as GFR < 30ml/min) is associated with the development of another devastating disease called nephrogenic systemic fibrosis. As HHT patients will require repeated scans throughout their lifetimes, this study will provide them a safer alternative.
Ten patients from the HHT clinic in whom the use of ferumoxytol as an MR agent is clinically indicated will be invited to participate in this study, which will determine if MR with ferumoxytol is able to detect and characterize vascular malformations in HHT.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The safety of the use of gadolinium based contrast agents in MR is a concern for the FDA, with risks of development of nephrogenic systemic fibrosis and the more recent discovery of accumulation of gadolinium in the brain in patients who have received multiple prior MR scans.
Hereditary hemorrhagic telangiectasia (HHT) manifests with multiple vascular malformations (VMs) in the skin, mucous membranes and solid organs affecting the spine, brain, liver, gastrointestinal tract, pancreas, and lungs. The disease has an autosomal dominant inheritance and affects 1 in 5000 individuals.
Cerebral vascular malformations occur in 23 % of HHT patients, with a bleeding risk of 0.5% per year. Pulmonary AVMs occur in 15-50% of HHT patients, with a complication rate of 50% ranging from fatal hemoptysis or hemothorax to stroke or cerebral abscess. Liver vascular malformations are present in 32-78% of HHT patients.
The rationale for screening for vascular malformations is detection of a treatable lesion prior to the development of a fatal complication. The international guidelines currently recommend different first line screening tests in each organ: MRI for cerebral VMs, transthoracic echocardiography for pulmonary VMs, endoscopy for gastrointestinal VMs, Doppler US or CT for liver VMs.
Contrast enhanced magnetic resonance angiography (CE-MRA) may play an important role in the simultaneous whole body screening of vascular malformations. The advantages of CE-MRA include visualization of the entire body vasculature in one examination, high spatial resolution comparable to CT, no ionizing radiation and easy of multiplanar reconstructions.
Substituting a conventional gadolinium based contrast agent (GBCA) with an ultra small, super paramagnetic iron oxide agent (USPIO) e.g ferumoxytol, will eliminate any potential risk of developing nephrogenic systemic fibrosis. Since 2009, ferumoxytol ('Feraheme' Advanced Magnetics, Cambridge, MA) has been FDA approved for the treatment of iron deficiency anemia in adult patients with chronic kidney disease. The results of prior studies suggest that ferumoxytol is comparable to standard GBCAs for CE- MRA. Our experience with use of ferumoxytol to date suggests that it will be a superior agent for detection of vascular malformations in a range of vascular territories and that it will be uniquely capable of interrogating multiple territories in one sitting, due to its highly stable intravascular residence time.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90095
- UCLA
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Definite diagnosis of HHT (clinically or genetically confirmed)
- Known or suspected AVMs in the brain, lung, and/or liver
- Use of ferumoxytol as an MR agent is clinically indicated
Exclusion Criteria:
- Age <18
- Unable to have MRI scan
- Prior adverse reaction to ferumoxytol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Feraheme group
All patients enrolled in the study will receive Feraheme MRI/MRA to detect vascular malformations.
Ferumoxytol in its standard concentration (510 mg in 17 cc) will be administered IV at 0.15-0.21
mg/kg prior to MRI/MRA.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Presence or absence of AVM
Time Frame: Immediate
|
Immediate
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Size of AVM
Time Frame: Immediate
|
Immediate
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Location of AVM
Time Frame: Immediate
|
Immediate
|
Overall image quality score
Time Frame: Immediate
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Immediate
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Artifact score
Time Frame: Immediate
|
Immediate
|
Vessel definition score
Time Frame: Immediate
|
Immediate
|
Number of AVM feeding arteries
Time Frame: Immediate
|
Immediate
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Dimension of largest AVM feeding artery
Time Frame: Immediate
|
Immediate
|
Number of AVM draining veins
Time Frame: Immediate
|
Immediate
|
Dimension of largest AVM draining vein
Time Frame: Immediate
|
Immediate
|
Dimension of aneurysmal sac
Time Frame: Immediate
|
Immediate
|
Collaborators and Investigators
Investigators
- Principal Investigator: Justin McWilliams, MD, University of California, Los Angeles
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Congenital Abnormalities
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Cardiovascular Abnormalities
- Vascular Malformations
- Telangiectasis
- Telangiectasia, Hereditary Hemorrhagic
- Hematinics
- Pharmaceutical Solutions
- Parenteral Nutrition Solutions
- Ferrosoferric Oxide
Other Study ID Numbers
- 15-001308
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hereditary Hemorrhagic Telangiectasia
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