Assessment of 18F-Florbetaben Whole-body PET for the Detection of Cardiac and Extracardiac Sites of Amyloid Deposits

NCT03616496 | Completed DMC

• 1 other identifier: 2018-004054-24
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Although being classified as a rare disease, cardiac amyloidosis constitutes an increasing cause of heart failure, which is often overlooked and thus poorly managed. Amyloidosis involves deposits of light chain immunoglobulins in the immunoglobulin light chain amyloidosis (AL) type, but it may also be of a hereditary type in mutated transthyretin amyloidosis (ATTRm) or of a senile type in wildtype transthyretin forms (ATTRwt). Myocardial biopsy remains a gold standard for definitive diagnosis but it is a traumatic technique which only provides information on a limited number of sampled sites. Useful but not fully specific signs of cardiac amyloidosis may also be provided by Magnetic Resonance Imaging or MRI (delayed retention imaging) and echocardiography (longitudinal strain pattern). Notwithstanding the above, relatively specific markers of amyloid plaques are now available in Positron Emission Tomography (PET). These markers are primarily fluorinated tracers which have been developed for the diagnosis of Alzheimer's disease. Two of these have already been the subject of feasibility studies in the setting of cardiac amyloidosis diagnosis, on a maximum of 10 amyloidosis patients but with very favorable results. The hypothesis is that one of these two tracers, Florbetaben labelled with Fluorine-18-Florbetaben (18F-Florbetaben) used in the study, has sufficiently strong and prolonged binding kinetics at the level of the amyloid plaques to allow: (i) achieving whole-body PET recordings and thus, (ii) identifying not only cardiac amyloidosis but also extracardiac binding sites, particularly those readily accessible to biopsy sampling. This hypothesis has been strengthened by a recent case report illustrating the ability of whole-body florbetaben-PET to image not only cardiac but also extra-cardiac sites of amyloid deposits (Clin Nucl Med. 2017;42(1):50-3).

Conditions

Cardiac Amyloidosis

Keywords

PET imaging; Cardiac Amyloidosis; Florbetaben; Heart failure; Cardiology

Outcome Measures

Primary Outcomes (1)

• Definitive diagnosis of cardiac ATTR- or AL-amyloidosis upon current diagnosis standard (including cardiac or extracardiac biopsies),

  The diagnosis will be made with standard parameters (including cardiac or extracardiac biopsies), Importantly, a " control " population, including patients with left ventricular hypertrophy definitively unrelated to amyloidosis (even for low to mild forms) will be added for the analysis (this hypertrophy is mandatory for reaching a comparable partial volume effect than with amyloidosis patients when recording myocardial PET activity).

  upon 24 months

Secondary Outcomes (5)

• To assess the diagnostic performance of whole-body PET/CT recordings, as reported in the main objective, to identify AL and ATTR amyloidosis individually.

  upon 24 months

• To determine whether (18)F-florbetaben whole-body PET/CT images can reveal extracardiac areas with increased activity

  upon 24 months

• To compare the cardiac kinetics of (18)F-florbetaben and an early myocardial retention index, within the first 10 minutes following injection, between patients with cardiac amyloidosis and the control population

  upon 24 month

• To determine whether most patients with true-positive MRI for cardiac amyloidosis

  upon 24 month

• To assess the intra- and inter-observer agreements for the analysis of (18)F-florbetaben whole-body PET/CT images.

  upon 24 month

Study Arms (3)

ATTR amyloidosis patients

EXPERIMENTAL

Intervention by this arm: PET/CT with injection of Neuraceq \[4 MegaBecquerel /Kilogram (MBq/kg)\], blood and urine sampling for protein electrophoresis, bone scintigraphy

Drug: Neuraceq PET/CT imaging

AL amyloidosis patients

EXPERIMENTAL

Intervention by this arm: PET with injection of Neuraceq (4 MBq/kg), blood and urine sampling for protein electrophoresis, bone scintigraphy

Drug: Neuraceq PET/CT imaging

Control subjects with aortic stenosis

ACTIVE COMPARATOR

Intervention by this arm: PET with injection of Neuraceq (4 MBq/kg), blood and urine sampling for protein electrophoresis, bone scintigraphy. Control subjects are patients with aortic stenosis and left ventricular hypertrophy treated by surgery or by Transcatheter Aortic Valve Implantation (TAVI)

Drug: Neuraceq PET/CT imaging

Interventions

Neuraceq PET/CT imaging DRUG

PET/CT with Neuraceq injection, blood and urine sampling for protein electrophoresis, bone scintigraphy for the three arm (if the exams are present in the patient's medical record and are less than 3 months old, they do not need to be repeated

Also known as: Bone scintigraphy, Blood and urine sampling for protein electrophoresis

AL amyloidosis patients; ATTR amyloidosis patients; Control subjects with aortic stenosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all study participants
• Person affiliated to or beneficiary of, a social security plan
• Person informed about study organization and having signed the informed consent
• For ATTR amyloidosis patients:
• left ventricular concentric hypertrophy with a diastolic septal thickness ≥ 15 mm at echography (as defined by the current distribution of this parameter in the ATTR patients involved in a French national cohort of the Henri Mondor Hospital),
• clearly positive bone scan (\> mild cardiac uptake) and/or concordant results at pathology of cardiac or extra-cardiac sites (Congo red-positive deposits under crossed polarized light and immunohistochemical staining for transthyretin).
• For AL amyloidosis patients:
• left ventricular concentric hypertrophy with a diastolic septal thickness ≥ 13 mm at echography (as defined by the current distribution of this parameter in the AL patients involved in the French national cohort of the Henri Mondor Hospital),
• significant cardiac disease evidenced by an increase in plasma N-Terminal ProBNP (or BNP) and/or in troponin T (or I), corresponding to a Mayo clinic score ≥ 2 ,
• concordant results at pathology of cardiac or extra-cardiac sites (Congo red-positive deposits under crossed polarized light and immunohistochemical staining for κ and λ immunoglobulin light chains).
• For control subjects:
• History of surgical or Transcatheter Aortic Valve Implantation (TAVI)treatment of aortic stenosis
• Matching with amyloidosis patients according to gender and age (± 5 years).
• Cardiac hypertrophy with a diastolic septal thickness ≥ 15 mm at echography when matching with an ATTR patient and ≥ 13 mm when matching with an AL patient.

You may not qualify if:

• Known allergy to the active substance and to any excipient for 18F-Florbetaben or for the bone scintigraphy radiotracer (99mTc-MDP)
• Pregnancy, breastfeeding and woman of childbearing age without effective contraception
• Person referred in articles L.1121-5 to L.1121-8 and L.1122-2 of the Public Health Code:
• Pregnant, parturient or breastfeeding woman
• Person deprived of liberty for judicial or administrative decision
• Person under psychiatric care
• Person admitted to health or social institution for other reasons than research
• Minor person (non-emancipated)
• Adult person under legal protection (any form of public guardianship)
• Adult person incapable of giving consent and not under legal protection
• No obvious cause of cardiac disease except for mild to moderate hypertension in all study subjects, for cardiac amyloidosis in the amyloidosis groups and for aortic stenosis in the control group
• Impossibility of performing 18F-Florbetaben PET (agitated, confused patient, etc.).
• Sever left ventricular dysfunction with an ejection fraction ≤ 35%
• Severe hepatic or renal failure.
• For control patients only: monoclonal gammopathy on a previous protein electrophoresis or ≥ mild cardiac uptake on a previous bone scintigraphy.

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

Chru Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Heart Failure

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Pierre-Yves MARIE, MD,PhD

  CHRU de NANCY BRABOIS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 27, 2018
• First Posted: August 6, 2018
• Study Start: June 6, 2019
• Primary Completion: January 30, 2025
• Study Completion: February 10, 2025
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)