Cardiac AmyloidosisEarly Phase 1NCT04105634
Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Light Chain Amyloidosis Using PET/CT
A Early Phase 1 study testing FNOS and Florbetaben in people with Cardiac Amyloidosis, run by University of Pennsylvania at 1 site in United States.
Trial summary
The research study is being conducted to test how two different types of Positron Emission Tomography (PET/CT) scans could be used to image a type of heart disorder called amyloidosis (AL). There will be two groups in the study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Amyloidosis
- What is being tested?
- FNOS and Florbetaben
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2019to 14 Oct 2024
- Phase
- Early 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
- Participants will be at least 18 years of age
- Have an established diagnosis of AL amyloidosis based on standard criteria and planning to start systemic therapy.
- Have cardiac involvement as defined by all of the following:
- Past documented or presently noted clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure
- Either an endomyocardial biopsy demonstrating AL amyloidosis or an echocardiogram demonstrating a mean left ventricular wall thickness at diastole >12mm in the absence of other causes (e.g. severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening
- NT-proBNP ≥ 650 pg/mL
Show all 11Show fewer
- Participants should fall into 1 of the following 2 categories:
- Treatment-naïve or have completed no more than 1 cycle of initial therapy, OR
- Relapsed after 1 or more prior therapies, and at least 6 months from last treatment
- Have serum free light chain (FLC) differential (defined as amyloid-forming FLC minus non-amyloid-forming FLC) ≥ 50 mg/L.
- Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.
Who cannot join
- Females who are pregnant or breast feeding at the time of the PET/CT scan will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential before the injection of radiotracer.
- Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
- Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
- Less than 6 months life expectancy as deemed by a treating physician
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Cardiac Amyloidosis Using Positron Emission Tomography (PET/CT)
The research study is being conducted to test how two different types of Positron Emission Tomography (PET/CT) scans could be used to image a type of heart disorder called amyloidosis (AL). There will be two groups in the study. One group will have PET/CT scans using an imaging drug called 18F-NOS and the other group will have PET/CT scans using a drug called Florbetaben. subject will be assigned to one of the groups when she/he agrees to be in the study.
Read the detailed description
Immunoglobulin light chain (LC) amyloidosis (AL) is an underdiagnosed monoclonal plasma cell proliferative disorder caused by extracellular deposition of AL fibrils in various tissues and organs, causing disease by progressively damaging the structure and function of the affected tissue/organ. The heart is the most commonly involved organ (~75%),9 and the extent and severity of cardiac involvement continue to be the main limitation for successful treatment. Although it remains high, the 6-month mortality rate has improved significantly over the last decade (24% vs. 37%; P<0.001) due to earlier diagnosis, better treatment options, and the advent of sensitive serologic biomarkers to assess for early treatment response,10 in particular serum free light chains (FLC), which permit the differentiation of patients who achieve complete response (CR) and very good partial response (VGPR) from those with partial or no response. N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP) has also become a key biomarker for detection and risk-stratification of patients with cardiac AL amyloidosis, and is now routinely employed in clinical trials as a surrogate end point for survival. A large retrospective landmark analysis established that achievement of a CR or VGPR at 6 months post-initiation of therapy, or achievement of an NTproBNP response 6 months post-initiation of therapy, defined as a 30% reduction and absolute reduction ≥ 300 pg/mL from baseline for subjects with baseline levels ≥ 650 pg/mL, was strongly associated with improved overall survival (insert Palladini et al, JCO 2012).
- Conditions
- Cardiac Amyloidosis
- Being tested
- FNOS, Florbetaben
- Medical subject headings
- Amyloid Neuropathies, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FNOSDrug
Also called [18F]-6-(2-fluoro-propyl)-4-methylpyridin-2-amine
The imaging drug used for this group is called 18F-NOS, it is an experimental imaging drug that has not yet been approved by the Food and Drug Administration (FDA) for use except in a research study. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care.
FlorbetabenDrug
Also called Neuraceq
The imaging drug used for this group is called Florbetaben, it is an FDA approved radioactive PET tracer used to image amyloid plaques in the body. Although not yet FDA approved for this purpose, it has already been used clinically to image amyloid in other parts of the body. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care.
| Study group | Role | What they receive |
|---|---|---|
| Inflammation group | Experimental | Patient diagnosed with Cardiac Amyloidosis Receives: Drug: FNOS |
| Amyloid group | Experimental | Patient diagnosed with Cardiac Amyloidosis Receives: Drug: Florbetaben |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy using PET/CT
Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy and describe the distributions of uptake values at each time point. Compute post-/pre-treatment fold change in [18F]NOS and Florbetaben uptake and describe its distribution.
Measured: 4 months
Secondary outcomes (3)
Describe fold changes in [18F]NOS uptake in patients who have a complete response or very good partial response vs patients who have a partial or no response to therapy at ~4 months.
Describe fold changes in [18F]NOS uptake in patients who have a complete response or very good partial response vs patients who have a partial or no response to therapy at ~4 months.
Measured: 4 months
Describe fold changes in [18F]NOS uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression
Describe fold changes in [18F]NOS uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression
Measured: 4 months
Describe fold changes in Florbetaben uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression
Describe fold changes in Florbetaben uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2019
- Study start1 Oct 2019
- Primary completion14 Oct 2024
- Study completion14 Oct 2024
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac AmyloidosisStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paco Bravo, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04105634
- Sponsor's protocol ID
- 833485
- Status last verified
- Nov 2024
- First submitted
- 18 Sep 2019
- Last updated
- 12 Nov 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Cardiac Amyloidosis Using Positron Emission Tomography (PET/CT)
- ClinicalTrials.gov ID
- NCT04105634
- Acronym / sponsor ID
- 833485
- Conditions
- Cardiac Amyloidosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 14 Oct 2024 (actual)
- Study completion
- 14 Oct 2024 (actual)
- First posted
- 26 Sep 2019 (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.
The research study is being conducted to test how two different types of Positron Emission Tomography (PET/CT) scans could be used to image a type of heart disorder called amyloidosis (AL). There will be two groups in the study. One group will have PET/CT scans using an imaging drug called 18F-NOS and the other group will have PET/CT scans using a drug called Florbetaben. subject will be assigned to one of the groups when she/he agrees to be in the study.
Detailed description
Immunoglobulin light chain (LC) amyloidosis (AL) is an underdiagnosed monoclonal plasma cell proliferative disorder caused by extracellular deposition of AL fibrils in various tissues and organs, causing disease by progressively damaging the structure and function of the affected tissue/organ. The heart is the most commonly involved organ (~75%),9 and the extent and severity of cardiac involvement continue to be the main limitation for successful treatment. Although it remains high, the 6-month mortality rate has improved significantly over the last decade (24% vs. 37%; P<0.001) due to earlier diagnosis, better treatment options, and the advent of sensitive serologic biomarkers to assess for early treatment response,10 in particular serum free light chains (FLC), which permit the differentiation of patients who achieve complete response (CR) and very good partial response (VGPR) from those with partial or no response. N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP) has also become a key biomarker for detection and risk-stratification of patients with cardiac AL amyloidosis, and is now routinely employed in clinical trials as a surrogate end point for survival. A large retrospective landmark analysis established that achievement of a CR or VGPR at 6 months post-initiation of therapy, or achievement of an NTproBNP response 6 months post-initiation of therapy, defined as a 30% reduction and absolute reduction ≥ 300 pg/mL from baseline for subjects with baseline levels ≥ 650 pg/mL, was strongly associated with improved overall survival (insert Palladini et al, JCO 2012).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inflammation group | Experimental | Drug: FNOSPatient diagnosed with Cardiac Amyloidosis |
| Amyloid group | Experimental | Drug: FlorbetabenPatient diagnosed with Cardiac Amyloidosis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Participants will be at least 18 years of age
- Have an established diagnosis of AL amyloidosis based on standard criteria and planning to start systemic therapy.
- Have cardiac involvement as defined by all of the following:
- Participants should fall into 1 of the following 2 categories:
- Have serum free light chain (FLC) differential (defined as amyloid-forming FLC minus non-amyloid-forming FLC) ≥ 50 mg/L.
Key exclusion criteria (4 listed)
- Females who are pregnant or breast feeding at the time of the PET/CT scan will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential before the injection of radiotracer.
- Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
- Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
- Less than 6 months life expectancy as deemed by a treating physician
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 |
|---|---|---|
| FNOSAlso: [18F]-6-(2-fluoro-propyl)-4-methylpyridin-2-amineThe imaging drug used for this group is called 18F-NOS, it is an experimental imaging drug that has not yet been approved by the Food and Drug Administration (FDA) for use except in a research study. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care. | Drug | Inflammation group |
| FlorbetabenAlso: NeuraceqThe imaging drug used for this group is called Florbetaben, it is an FDA approved radioactive PET tracer used to image amyloid plaques in the body. Although not yet FDA approved for this purpose, it has already been used clinically to image amyloid in other parts of the body. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care. | Drug | Amyloid group |
Primary outcome
Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy using PET/CT
Time frame: 4 months
Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy and describe the distributions of uptake values at each time point. Compute post-/pre-treatment fold change in [18F]NOS and Florbetaben uptake and describe its distribution.
3 secondary outcomes
Describe fold changes in [18F]NOS uptake in patients who have a complete response or very good partial response vs patients who have a partial or no response to therapy at ~4 months.
Time frame: 4 months
Describe fold changes in [18F]NOS uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression
Time frame: 4 months
Describe fold changes in Florbetaben uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression
Time frame: 4 months
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
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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.
Paco Bravo principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing FNOS and Florbetaben in people with Cardiac Amyloidosis, run by University of Pennsylvania 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 11 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: stopped early, as of the sponsor's last update on 12 Nov 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 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was stopped early (reason given: Low accrual). Results are not available in the source record.
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?
Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy using PET/CT (time frame: 4 months). 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 12 Nov 2024.