Hereditary Hemorrhagic TelangiectasiaPhase 1NCT02977637
MRA With Feraheme in HHT
A Phase 1 study testing Feraheme MRI/MRA in people with Hereditary Hemorrhagic Telangiectasia, run by University of California, Los Angeles at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia
- What is being tested?
- Feraheme MRI/MRA
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Nov 2018
- Phase
- Phase 1
- 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
- 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
Who cannot join
- Age <18
- Unable to have MRI scan
- Prior adverse reaction to ferumoxytol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- Being tested
- Feraheme MRI/MRA
- Keywords
- hht, hereditary, hemorrhagic, telangiectasia, feraheme
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic, Telangiectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Feraheme MRI/MRAProcedure or surgery
Also called Ferumoxytol
| Study group | Role | What they receive |
|---|---|---|
| Feraheme group | Experimental | 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. Receives: Procedure: Feraheme MRI/MRA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence or absence of AVM
Measured: Immediate
Secondary outcomes (10)
Size of AVM
Measured: Immediate
Location of AVM
Measured: Immediate
Overall image quality score
Measured: Immediate
Artifact score
Measured: Immediate
Vessel definition score
Measured: Immediate
Number of AVM feeding arteries
Measured: Immediate
Dimension of largest AVM feeding artery
Measured: Immediate
Number of AVM draining veins
Measured: Immediate
Dimension of largest AVM draining vein
Measured: Immediate
Dimension of aneurysmal sac
Measured: Immediate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionNov 2018
- Study completionNov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Justin McWilliams, MD, University of California, Los Angeles
- Investigators
- Justin McWilliams, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02977637
- Sponsor's protocol ID
- 15-001308
- Status last verified
- Jan 2019
- First submitted
- 28 Nov 2016
- Last updated
- 25 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Ferumoxytol (Feraheme) for Whole Body Magnetic Resonance Angiography in Hereditary Hemorrhagic Telangiectasia
- ClinicalTrials.gov ID
- NCT02977637
- Acronym / sponsor ID
- 15-001308
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- Keywords
- hht, hereditary, hemorrhagic, telangiectasia, feraheme
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Nov 2016
- Primary completion
- Nov 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 30 Nov 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.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Feraheme group | Experimental | Procedure: Feraheme MRI/MRAAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- Age <18
- Unable to have MRI scan
- Prior adverse reaction to ferumoxytol
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 |
|---|---|---|
| Feraheme MRI/MRAAlso: Ferumoxytol | Procedure or surgery | Feraheme group |
Primary outcome
Presence or absence of AVM
Time frame: Immediate
10 secondary outcomes
Size of AVM
Time frame: Immediate
Location of AVM
Time frame: Immediate
Overall image quality score
Time frame: Immediate
Artifact score
Time frame: Immediate
Vessel definition score
Time frame: Immediate
Number of AVM feeding arteries
Time frame: Immediate
Dimension of largest AVM feeding artery
Time frame: Immediate
Number of AVM draining veins
Time frame: Immediate
Dimension of largest AVM draining vein
Time frame: Immediate
Dimension of aneurysmal sac
Time frame: Immediate
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 Jan 2019.
- 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. This study is not recruiting at the moment.
Justin McWilliams, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Feraheme MRI/MRA in people with Hereditary Hemorrhagic Telangiectasia, run by University of California, Los Angeles 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 3 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 Jan 2019. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Presence or absence of AVM (time frame: Immediate). 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 Jan 2019.