Molecular Imaging of Myocardial Fibrosis in Cardiac Amyloidosis

NCT05619302 | Completed Phase 3 FDA Drug

• 1 other identifier: 2022A012856
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of our pilot study is to determine whether fibrosis in the heart can be measured with \[68Ga\]CBP8, a positron emission tomography (PET) probe, using PET/magnetic resonance imaging (MRI) imaging, in 30 individuals with documented cardiac amyloidosis. The investigators will also enroll 15 individuals with recent myocardial infarction and 15 individuals with hypertrophic cardiomyopathy as positive controls for fibrosis, and the investigators will enroll 5 individuals without cardiovascular disease to undergo \[68Ga\]CBP8 PET/MRI imaging as a healthy control group. The primary hypothesis of this study is that \[68Ga\]CBP8 will bind to interstitial collagen and quantify myocardial fibrosis in patients with cardiac amyloidosis. The investigators hypothesize that \[68Ga\]CBP8 uptake will be greater in patients with cardiac amyloidosis, myocardial fibrosis, and hypertrophic cardiomyopathy than in healthy controls. Secondly, the investigators also hypothesize that \[68Ga\]CBP8 activity more strongly correlates with standard MRI measures in patients with recent myocardial infarction and hypertrophic cardiomyopathy (where extracellular expansion is caused by myocardial fibrosis/collagen deposition) than in patients with cardiac amyloidosis (where myocardial fibrosis is combined with infiltration).

Conditions

Cardiac Amyloidosis

Keywords

Amyloidosis; Cardiac; Heart; Imaging; Diagnosis

Outcome Measures

Primary Outcomes (2)

• Mean Standardized Uptake Value (SUVmean) of [68Ga]CBP8 uptake in the heart

  Standardized uptake value (SUV) mean is defined as the mean \[68Ga\]CBP8 concentration measured within the left ventricular myocardium multiplied by the decay-corrected amount of injected \[68Ga\]CBP8 normalized to patient weight. We expect SUVmean will be greater in patients with cardiac amyloidosis and myocardial infarction compared with healthy control subjects.

  1 day

• Extracellular volume from clinically performed simultaneous cardiac MRI

  We will correlate \[68Ga\]CBP8 uptake with standard MRI extracellular volume (ECV) measures. We expect \[68Ga\]CBP8 activity to more strongly correlate with MRI in patients with myocardial infarction than cardiac amyloidosis.

  1 day

Study Arms (4)

[68Ga]CBP8 PET/MRI Amyloid Subjects

EXPERIMENTAL

Individuals with documented cardiac amyloidosis will undergo \[68Ga\]CBP8 PET/MRI.

Drug: [68Ga]CBP8 PET/MRI

[68Ga]CBP8 PET/MRI Recent Myocardial Infarction Subjects

ACTIVE COMPARATOR

Individuals with recent myocardial infarction will undergo \[68Ga\]CBP8 PET/MRI.

Drug: [68Ga]CBP8 PET/MRI

[68Ga]CBP8 PET/MRI Healthy Controls

PLACEBO COMPARATOR

Individuals without documented cardiovascular disease will undergo \[68Ga\]CBP8 PET/MRI.

Drug: [68Ga]CBP8 PET/MRI

[68Ga]CBP8 PET/MRI Hypertrophic Cardiomyopathy Subjects

ACTIVE COMPARATOR

Individuals with hypertrophic cardiomyopathy will undergo \[68Ga\]CBP8 PET/MRI.

Drug: [68Ga]CBP8 PET/MRI

Interventions

[68Ga]CBP8 PET/MRI DRUG

Simultaneous cardiac PET/MRI images will be obtained following injection of \[68Ga\]CBP8

Also known as: No other names

[68Ga]CBP8 PET/MRI Amyloid Subjects; [68Ga]CBP8 PET/MRI Healthy Controls; [68Ga]CBP8 PET/MRI Hypertrophic Cardiomyopathy Subjects; [68Ga]CBP8 PET/MRI Recent Myocardial Infarction Subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Willing and able to provide consent
• AL-CA: Diagnosis of systemic light chain amyloidosis by standard criteria: Immunofixation of serum, serum free light chain (FLC) assay, a biopsy of fat pad/bone marrow, or organ biopsy, followed by typing of the light chain using immunohistochemistry or immunogold assay with confirmation by mass spectroscopy as needed AND
• Proof of cardiac involvement by AL amyloidosis
• Abnormal cardiac biomarkers: abnormal high sensitivity TnT 5th generation levels (\> 15 ng/L) or abnormal age-appropriate NT-proBNP (abnormal values: \< 50 years: \> 450 pg/ml; 50-75 years: \> 900 pg/ml; \> 75 years: \> 1800 pg/ml) OR
• Abnormal echocardiogram (wall thickness \> 12 mm in the absence of other causes of increased LV wall thickness) OR
• Abnormal CMR (wall thickness \> 12 mm, extracellular volume \> 0.40 or typical CMR appearance of cardiac amyloidosis with difficulty nulling images and non-coronary distribution late gadolinium enhancement) OR
• Positive endomyocardial biopsy
• Age \> 18 years
• Willing and able to provide consent
• ATTR-CA: Diagnosis of either wildtype or hereditary transthyretin cardiac amyloidosis by standard criteria: Endomyocardial biopsy followed by typing of the transthyretin amyloidosis using immunohistochemistry or immunogold assay with confirmation by mass spectroscopy as needed
• Extracardiac biopsy with typical cardiac imaging findings
• Hereditary ATTR amyloidosis by genetic testing OR
• Grade 2 or grade 3 myocardial uptake of 99mTc-PYP if AL amyloidosis is excluded
• Age \> 18 years

You may not qualify if:

• Dialysis
• NYHA (New York Heart Association) Class IV
• Acute myocardial infarction within 6 weeks
• Pregnancy or nursing
• History of adverse events from or allergy to gadolinium contrast media
• Hemodynamic instability
• Severe claustrophobia despite use of sedatives
• Decompensated heart failure (unable to lie flat for 1 hour)
• Concomitant clinically significant non-ischemic non-amyloid heart disease (valvular heart disease or dilated cardiomyopathy)
• Body weight over limit for MRI table (\>300 lbs)
• Contraindications for MRI (including non-compatible cardiac implantable electronic devices, drug infusion pumps, and metallic or electric implants)
• Any other reason determined by the investigator to be unsuitable for the study

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.

  PMID: 31161770 BACKGROUND

• Desogere P, Tapias LF, Rietz TA, Rotile N, Blasi F, Day H, Elliott J, Fuchs BC, Lanuti M, Caravan P. Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. J Nucl Med. 2017 Dec;58(12):1991-1996. doi: 10.2967/jnumed.117.193532. Epub 2017 Jun 13.

  PMID: 28611243 BACKGROUND

• Desogere P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.

  PMID: 28381537 BACKGROUND

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Amyloidosis; Disease

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; Proteostasis Deficiencies; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sharmila Dorbala, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Nuclear Cardiology

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 16, 2022
• Study Start: January 3, 2023
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)