18F-florbetaben PET-CT to Non-invasively Diagnose Cardiac AL Amyloidosis

Last updated: September 16, 2023
Sponsor: Fondazione Toscana Gabriele Monasterio
Overall Status: Active - Recruiting

Phase

N/A

Condition

Amyloidosis

Circulation Disorders

Treatment

18F-florbetaben PET/CT

Clinical Study ID

NCT06048601
PETAL2023
  • Ages 18-95
  • All Genders

Study Summary

Amyloidoses are systemic or acquired disorders characterized by the deposition in the extracellular spaces of amyloid fibers formed by proteins codified by mutated genes or non-mutated but misfolded proteins. Cardiac involvement in amyloidosis is an important determinant of the clinical presentation and can be found in patients with amyloid light-chain (AL) or transthyretin (ATTR) amyloidosis, the latter due to the deposition of normal proteins (formerly known as senile amyloidosis) or mutated proteins. Cardiac amyloidosis (CA) has a poor prognosis that further worsens if the diagnosis and treatment are delayed. Nuclear medicine techniques have emerged as important tools for the diagnosis and characterization of CA. It has been recently demonstrated that cardiac uptake of bone tracers allows to identify the deposition of transthyretin in the heart, while it is not useful for the diagnosis of AL-CA, which currently requires the histological demonstration of amyloid fibers in a tissue sample taken with invasive procedures such as an endomyocardial biopsy. Recently, some PET tracers developed to identify beta-amyloid deposits in the brain proved able to detect an uptake even in the heart; nonetheless their possible use to diagnose CA is still debated. One of those tracers is florbetaben labelled with 18F, which displays a high binding affinity with beta-amyloid in the brain, while the experience on its use to identify extracranial amyloid deposits is still limited. Three studies have reported a cardiac uptake of 18F-florbetaben in AL or ATTR amyloidosis. Tracer uptake could be detected starting from 15 minutes after tracer administration. In a case series of 60 patients (20 with AL-CA, 20 with ATTR-CA and 20 with CA suspected but excluded) we demonstrated that the evidence of a myocardial uptake in a late acquisition can effectively discriminate AL- from ATTR-CA or other conditions. Indeed, patients with AL-CA displayed an intense and persistent myocardial uptake in static acquisitions at all time points, while patients with ATTR-CA and those without CA displayed a rapid reduction of the uptake after the early acquisition.

This study aims to compare the performance of PET/CT with 18F-florbetaben to diagnose AL-CA compared with the current diagnostic standard, which requires a tissue biopsy.

Primary objective:

To define the agreement (with its 95% confidence interval) between two diagnostic approaches to the diagnosis of AL-CA in patients with a monoclonal protein: the traditional invasive approach and a non-invasive approach using the visual assessment of 18F-florbetaben PET/TC.

Secondary objectives:

  • To define the diagnostic performance of PET/CT with 18F-florbetaben (visual evaluation) in terms of sensitivity, specificity, positive and negative predictive value;

  • To define cut-offs from myocardial uptake quantification to confirm or discard AL-CA among patients with suspected CA and a monoclonal protein, compared to the standard diagnostic algorithm, from quantitative uptake values;

  • To assess the changes in the degree of myocardial 18F-florbetaben uptake over 12 months in patients with AL-CA;

  • To assess the safety and tolerability of PET/CT with 18F-florbetaben in patients evaluated for suspected CA.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Men and women aged >18 years;
  • Ability to understand, sign and date the informed consent;
  • NT-proBNP values> 332 ng/L in the absence of renal in-sufficiency or atrialfibrillation or mean left ventricular wall thickness >12 mm on echocardiogram and / ora pat-tern of circumferential or diffuse late gadolinium en-hancement and/or BNP >81ng/L, in a clinical setting seemed compatible with CA by experienced doctors.

Exclusion

Exclusion Criteria:

  • Hypersensitivity to the active principle or any excipient listed in the paragraph 6.1of the Summary of Product Characteristics (RCP) of Neuraceq®;
  • Severe chronic kidney disease (estimated glomerular filtra-tion rate <30 mL/min/1.73m2);
  • Performing a PET/CT or scintigraphic exam within 24 hours;
  • Impossibility to lay flat for about 60 minutes;
  • New York Heart Association (NYHA) class IV;
  • Pregnancy or breastfeeding, women with childbearing po-tential and sexually active notemploying highly effective contraceptive methods with a low dependency on the user (from the screening to the end of visit 1), which include: i. abstinence, ii. sexualintercourse only with same-sex part-ners, iii. monogamous relationship with a partnerwith pri-or vasectomy, iv. intrauterine device, v. combined hormo-nal contraceptionincluding estrogens and progesteron-like hormones plus the inhibition of ovulation (oral, intravagi-nal or transdermal), vi. hormonal contraception based onprogesterone-like compounds plus the inhibition of ovula-tion (oral, injectable,implantable), viii. intrauterine device with hormone release. The highly effectivecontraceptive measures above are not required for women made sterile by surgical means (for example through tube ligation, hys-terectomy, bilateral salpingectomy, bilateralovariectomy) or after the menopause, defined as 12 months of spontane-ous amenorrheawithout another clinical cause and with el-evated FSH levels in agreement with theexpected values for the menopause. For patients with true abstinence or with justsame-sex partners, contraception is not required, as far as this is in line with theirpreferred and habitual lifestyle. Periodical abstinence (for example, estimate of thetiming of ovulation or assessment of body temperature) and coitus interruptus are notacceptable contraceptive methods. If a patient stops to be abstinent, she must use thehighly effective contraceptive methods above. The pregnancy status in women potentially fertile will be checked through the measurementof beta human gonado-tropin on the serum and repeated at the end of the study;
  • Participation to a study involving the administration of an experimental drug within 30 days from the screening or 5 half-lives of the study drug, whichever the longest;
  • Lack of informed consent or impossibility to complete study procedures.

Study Design

Total Participants: 150
Treatment Group(s): 1
Primary Treatment: 18F-florbetaben PET/CT
Phase:
Study Start date:
January 26, 2023
Estimated Completion Date:
January 31, 2025

Connect with a study center

  • Fondazione Toscana Gabriele Monasterio

    Pisa,
    Italy

    Active - Recruiting

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