Clinical trial NCT03040427
Conditions: Cardiac Amyloidosis
Keywords: F-18 florbetapir Amyvid PET scan Early detection
Sponsor: The Cleveland Clinic
Start date: 2017-01-01; Completion date: 2019-08-21
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The investigators postulate that F-18 florbetapir will show improved detection of cardiac amyloidosis over conventional non-invasive imaging techniques, particularly in early disease.

Detailed description:
F-18 florbetapir is currently used for the early detection of brain amyloid (Alzheimer's disease). The hypothesis is that F-18 florbetapir will detect amyloid deposition in myocardium prior to current non-invasive diagnostic measures, particular electrocardiography with strain and technetium pyrophosphate scintigraphy. The investigators intend to use F-18 florbetapir and assess its correlation between standard non-invasive diagnostic modalities.

Arms: arm 1: The participants will undergo F-18 florbetapir PET scan.
Interventions: intervention 1: F-18 florbetapir
Intervention descriptions: intervention 1: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid).

Protocol documents:
Prot_SAP_000.pdf: 
F-18 Florbetapir in TTR Amyloidosis - Protocol 
                   
 
Sperry, B; Ikram, A; Jaber, W (© Cleveland Clinic Foundation) 
 
1 of 4 
 
 
Cleveland Clinic Foundation 
Department of Cardiovascular Medicine 
STUDY PROPOSAL 
 
NCT# 03040427 
Title: The role of F-18 florbetapir in the early 
detection of transthyretin cardiac amyloidosis 
 
Principal Investigator: Wael A. Jaber M.D. jaberw@ccf.org 
Co-Investigator: Brett Sperry M.D. sperryb@ccf.org 
Co-Investigator: Asad Ikram M.D. ikrama@ccf.org 
Co-Investigator: Mazen Hanna, M.D. hannam@ccf.org 
 
 
Protocol version: 3.0 
Protocol date: 05/25/2016 
Study site(s): Cleveland Clinic 
CCF IRB #: 16-960 
Approval Date: 08/22/2016 
Expiration Date: 08/04/2017 


F-18 Florbetapir in TTR Amyloidosis - Protocol 
                   
 
Sperry, B; Ikram, A; Jaber, W (© Cleveland Clinic Foundation) 
 
2 of 4 
 
Background: The gold standard to diagnose cardiac involvement in amyloidosis is 
endomyocardial biopsy. Non-invasive diagnostic modalities have become more 
commonplace in the recent past. Echocardiography with strain imaging, cardiac MRI 
and technetium-99m pyrophosphate (TcPYP) nuclear SPECT scintigraphy are often 
used. TcPYP is a bone radiotracer that binds to calcium in amyloid fibrils and 
demonstrates myocardial uptake in cases of TTR amyloidosis only. This tracer is 
FDA approved for imaging in cardiac amyloidosis, yet it is a non-specific tracer with 
unclear sensitivity and specificity in early disease. In addition, there is no current 
nuclear tracer that can be used for AL amyloidosis. 
Florbetapir F-18 is a radiotracer approved by the FDA for the use in positron 
emission tomography (PET) imaging of cerebral amyloid deposits for Alzheimer 
diseases. With regard to cardiac disease, one small study has confirmed the uptake 
of Florbetapir in both ATTR and AL cardiac amyloidosis.[1] Similar to Alzheimer 
disease, we postulate that Florbetapir will show improved detection of cardiac 
amyloidosis over conventional non-invasive imaging techniques, particularly in early 
disease.  
Our hypothesis is that F-18 florbetapir will detect amyloid deposition in myocardium 
prior to current non-invasive diagnostic measures, particularly echocardiography 
with strain and technetium pyrophosphate scintigraphy. We intend to use Florbetapir 
to assess the correlation between the standard TcPYP scintigraphy with this novel 
imaging modality. Additionally, we would like to examine the ability of florbetapir to 
detect early cardiac involvement by imaging patients with extra-cardiac biopsy 
proven TTR amyloidosis. 
 
Study Aim 
1) To assess the role of Florbetapir in the early detection of cardiac amyloidosis. 
2) To assess the correlation between TcPYP scintigraphy and F-18 florbetapir  
 
Significance of the Study  
This tracer is currently used for the early detection of brain amyloid (Alzheimer's 
disease). Early detection of Alzheimer disease is paramount, as treatment options 
are most beneficial when diagnosed early. Several recent studies support early 
amyloid detection by brain PET imaging using Florbetapir. This concept parallels the 
significance of this tracer in cardiac amyloidosis. As novel therapies evolve for 
cardiac amyloidosis, early detection of end organ involvement is essential as 
treatment options are most beneficial when started early. In addition, a non-invasive 
sensitive tracer will allow for monitoring of disease progression with treatment and 
may be used as a surrogate endpoint in future studies. 
This study will allow us to identify the sensitivity and specificity of this tracer and 
compare it to technetium pyrophosphate. In addition, we can subsequently follow 
patients who have uptake of florbetapir in the myocardium to see if they develop 
clinical events such as new heart failure or echocardiographic findings to suggest 
presence of cardiac disease. 


F-18 Florbetapir in TTR Amyloidosis - Protocol 
                   
 
Sperry, B; Ikram, A; Jaber, W (© Cleveland Clinic Foundation) 
 
3 of 4 
 
Methods 
This is a prospective, study that will recruit patients at Cleveland Clinic. 
Inclusion Criteria: 
1. Patients with extra-cardiac biopsy proven AL or ATTR amyloidosis  
2. Patients with a ratio of affected to unaffected free light chains >5 or free light 
chain difference of >50 
Exclusion Criteria: 
1. Echocardiographic evidence of cardiac amyloidosis with septal and posterior 
wall thickness ≥ 13mm  
2. Contraindication to florbetapir or its components  
3. Refusal to participate in the study 
Control group: 
1. We will also include 10 “control” patients without amyloidosis who had a 
negative extra-cardiac biopsy for amyloidosis. 
 
Patients will undergo PET/MRI imaging with florbetapir. The result will be available 
clinically and released to the provider. Patients will be followed as above. 
 
Logistics: 
 The amyloidosis clinical research fellow will screen patients and contact them, 
notifying them of the study 
 HVI clinical research nurse will consent patient at the time of regularly 
scheduled outpatient visit or TcPYP scan 
 Patient will be scheduled for F-18 florbetapir PET 
 Patient will undergo F-18 florbetapir PET 
o Radiotracer will be supplied without cost from Avid pharmaceuticals 
o Siemens PETNET will process the tracer in the on-site cyclotron. This 
is already being done at Cleveland Clinic for brain imaging in 
Alzheimer’s disease 
 The study PI and co-investigator will interpret images 
 
Sample size: We aim to enroll 40 patients, as Avid pharmaceuticals have agreed to 
provide us with 40 doses of florbetapir. 
 
Data Analysis: Images will be interpreted by two experienced readers blinded to 
clinical data and TcPYP scintigraphy results. Image will be read with both semi-
quantitative measures (17 segment model with uptake graded 0-4) and quantitatively 
(with segmental uptake values). 
Patient Risk: There is risk carried by the radiation for the scan. Each F-18 
florbetapir scan is dosed at 10mCi and estimated to deliver an equivalent dose of 
radiation of 7 mSv based on dosing for a 70kg person. Based upon the BEIR VII 
preferred model, overall cancer incidence given this amount of radiation per nuclear 


F-18 Florbetapir in TTR Amyloidosis - Protocol 
                   
 
Sperry, B; Ikram, A; Jaber, W (© Cleveland Clinic Foundation) 
 
4 of 4 
 
scan for a 60 year old was calculated to be 0.034% for males and 0.062% for 
females. This was calculated using Table 12D-1 from the BEIR VII report (see 
appendix) which reports the incidence of cancer cases based upon 100mSv 
equivalent doses per 100,000 persons exposed. The lifetime risk for cancer mortality 
is 0.022% for males and 0.029% for females per scan using Table 12D-2. 
In addition, there is a risk of adverse reaction. In one trial, one patient with AL 
amyloidosis currently undergoing chemotherapy developed nausea during the scan. 
[1] There were no reported adverse events in the other study. [2] In the FDA 
approval of florbetapir, there were “no serious adverse reactions in the studies and 
the reported adverse reactions were predominantly mild to moderate in severity.” 
Variables:  
 Clinical variables will be collected including age, sex, race, BMI, hypertension, 
diabetes, hyperlipidemia, coronary artery disease 
 Echocardiographic variables including LA/LV/RA/RV volumes, LV mass, anterior 
and posterior wall thickness, LVIDD, LVISD, EF, E velocity, A velocity, 
deceleration time, septal and lateral e`, RVSP, valve lesion severity, RV s`, RV 
FAC, LV and RV longitudinal strain 
 Laboratory variables including CBC, CMP, troponin T and NT-proBNP 
 Florbetapir-PET variables including segmental semiquantitative scores and SUVs 
 
 
References: 
1. Dorbala, S., et al., Imaging cardiac amyloidosis: a pilot study using (1)(8)F-
florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging, 2014. 
41(9): p. 1652-62. 
2. Osborne, D.R., et al., A routine PET/CT protocol with simple calculations for 
assessing cardiac amyloid using 18F-Florbetapir. Frontiers in Cardiovascular 
Medicine, 2015. 2.