Molecular Imaging of Primary Amyloid Cardiomyopathy
MICA
2 other identifiers
interventional
171
1 country
1
Brief Summary
Cardiac amyloidosis is a major cause of early treatment-related death and poor overall survival in individuals with systemic light chain amyloidosis. This project will develop a novel approach to visualize cardiac amyloid deposits using advanced imaging methods. The long-term goal of this work is to identify the mechanisms of cardiac dysfunction, in order to guide the development of novel life-saving treatments.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Apr 2016
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 22, 2015
CompletedFirst Posted
Study publicly available on registry
December 29, 2015
CompletedStudy Start
First participant enrolled
April 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
November 14, 2025
November 1, 2025
11.8 years
December 22, 2015
November 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Change in F-18 florbetapir myocardial retention index from baseline to 6 months and 12 months
quantitative measure of F-18 florbetapir uptake by the heart muscle
Baseline, 6 and 12 months
Change in Serum oxidative stress markers from baseline to 6 months and 12 months
serum F-2 isoprostane and peroxynitrite levels
Baseline, 6 and 12 months
Change in Myocardial oxidative metabolism markers from baseline to 6 months
K mono and coronary flow reserve obtained by C-11 acetate PET/CT at rest and stress
Baseline and 6 months
Change in Magnetic resonance imaging markers from baseline to 6 months and 12 months
Extracellular volume index, T-1 mapping, late gadolinium enhancement, global strain, left ventricular mass
Baseline, 6 and 12 months
Secondary Outcomes (3)
Change in Myocardial energy efficiency from baseline to 6 months
Baseline and 6 months
Light Chain Toxicity
Baseline
Understand the role of gut microbiota and heavy metals in the pathogenesis of AL Amyloidosis
Baseline
Study Arms (5)
Active AL cardiac amyloidosis
EXPERIMENTAL75 individuals with light chain systemic amyloidosis with active plasma cell dyscrasia and cardiac involvement will undergo a research F-18 florbetapir PET, C-11 acetate PET, and MRI of blood of the heart, as well as the heavy metal analysis of the blood at baseline, 6 months and 12 months after initiation of chemotherapy. 25 of these individuals will also undergo a N-13 ammonia PET scan of the heart following supine bicycle stress at baseline and at 6 months after initiation of chemotherapy.
Remission AL cardiac amyloidosis
ACTIVE COMPARATOR25 individuals with light chain systemic amyloidosis with cardiac involvement and plasma cell dyscrasia in hematological remission (complete hematological remission or very good partial response-differential free light chain (dFLC)\<40 mg/dL for \> 1 year prior to enrollment) will undergo a research F-18 florbetapir PET, C-11 acetate PET, and MRI scan of the heart as well as a heavy metal analysis of the blood at baseline.
Active AL Pre-CMP
EXPERIMENTAL36 individuals with light chain systemic amyloidosis with active plasma cell dyscrasia and without cardiac involvement will undergo a research F-18 florbetapir PET, C-11 acetate PET, and MRI of the heart, as well as a heavy metal analysis of the blood at baseline. At 6 months they will undergo a research MRI of the heart and at 12 months they will have a clinical follow up. Subjects with contraindications to Cardiac MRI or gadolinium contrast may still be eligible for study participation.
Multiple Myeloma Controls
NO INTERVENTION25 individuals with diagnosis of multiple myeloma without concomitant amyloidosis by standard criteria will undergo urine and blood testing only.
Heart Failure
EXPERIMENTAL10 individuals with diagnosis of heart failure without amyloidosis by standard criteria will undergo a research F-18 florbetapir PET, C-11 acetate PET, and MRI of the heart, as well as a heavy metal analysis of the blood at baseline..
Interventions
F-18 florbetapir PET scan, C-11 acetate PET scan
Cardiac MRI with gadolinium contrast.
N-13 ammonia PET scan following supine bicycle stress.
Eligibility Criteria
You may qualify if:
- Age \> 18 years
- Diagnosis of light chain amyloidosis by standard criteria (immunofixation of serum and urine, IgG 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)
- For subjects traveling from out of town referred for systemic AL therapy based on clinical evaluation and laboratory testing, but, pending biopsy results, study enrollment and procedures may begin before official confirmation of biopsy results. If biopsy is negative for AL amyloidosis, subject will be considered a screen failure. There will be no more than 10 subjects who fall under this screen failure for the duration of the study.
- Subjects with localized amyloid deposition and non-systemic AL disease will be eligible for enrollment in group D.
- Willing and able to provide consent
You may not qualify if:
- Hemodynamic instability
- Decompensated heart failure (unable to lie flat for 1 hour)
- Concomitant non-ischemic non-amyloid heart disease (valvular heart disease or dilated cardiomyopathy)
- Known obstructive epicardial coronary artery disease with stenosis \> 50% in any single territory
- Severe claustrophobia despite use of sedatives
- Presence of MRI contraindications such as metallic implants (pacemaker or ICD) at the time of study enrollment except for Control Heart Failure subjects. Control HF subjects with no devices, or, with strictly MR compatible devices will be eligible to undergo MRI.
- Significant renal dysfunction with estimated glomerular filtration rate \< 30 ml/min/m2 within 14 days of each cardiac MRI study. Subjects who develop renal dysfunction over the course of the study, meeting criteria listed above, will be excluded from the cardiac MRI scan except for control HF subjects. These subjects with eGFR \< 30 ml/min/1.73 m2 will undergo MRI without gadolinium contrast.
- Subjects on dialysis will be excluded
- Pregnant state. For women in child bearing age, a urine pregnancy test will be performed prior to the PET and the cardiac MRI studies
- Documented allergy to F-18 florbetapir, C-11 acetate or gadolinium.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Brigham and Women's Hospitallead
- National Institutes of Health (NIH)collaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- American Heart Associationcollaborator
Study Sites (1)
Brigham and Womens' Hospital
Boston, Massachusetts, 02421, United States
Related Publications (5)
Benz DC, Clerc OF, Cuddy SAM, Singh V, Kijewski MF, Bianchi G, Yee AJ, Ruberg FL, Jerosch-Herold M, Kwong RY, Di Carli MF, Liao R, Falk RH, Dorbala S. Changes in Myocardial Light Chain Amyloid Burden After Plasma Cell Therapy. JACC Cardiovasc Imaging. 2025 Dec;18(12):1363-1374. doi: 10.1016/j.jcmg.2025.07.017. Epub 2025 Sep 12.
PMID: 40938234DERIVEDClerc OF, Cuddy SAM, Jerosch-Herold M, Benz DC, Katznelson E, Canseco Neri J, Taylor A, Kijewski MF, Bianchi G, Ruberg FL, Di Carli MF, Liao R, Kwong RY, Falk RH, Dorbala S. Myocardial Characteristics, Cardiac Structure, and Cardiac Function in Systemic Light-Chain Amyloidosis. JACC Cardiovasc Imaging. 2024 Nov;17(11):1271-1286. doi: 10.1016/j.jcmg.2024.05.004. Epub 2024 Jul 10.
PMID: 39001736DERIVEDKatznelson E, Jerosch-Herold M, Cuddy SAM, Clerc OF, Benz DC, Taylor A, Rao S, Kijewski MF, Liao R, Landau H, Yee AJ, Ruberg FL, Di Carli MF, Falk RH, Kwong RY, Dorbala S. Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study. Front Cardiovasc Med. 2024 May 30;11:1371810. doi: 10.3389/fcvm.2024.1371810. eCollection 2024.
PMID: 38873265DERIVEDCuddy SAM, Jerosch-Herold M, Falk RH, Kijewski MF, Singh V, Ruberg FL, Sanchorawala V, Landau H, Maurer MS, Yee AJ, Bianchi G, Di Carli MF, Liao R, Kwong RY, Dorbala S. Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy. JACC Cardiovasc Imaging. 2022 Apr;15(4):594-603. doi: 10.1016/j.jcmg.2021.09.032. Epub 2021 Dec 15.
PMID: 34922860DERIVEDCuddy SAM, Bravo PE, Falk RH, El-Sady S, Kijewski MF, Park MA, Ruberg FL, Sanchorawala V, Landau H, Yee AJ, Bianchi G, Di Carli MF, Cheng SC, Jerosch-Herold M, Kwong RY, Liao R, Dorbala S. Improved Quantification of Cardiac Amyloid Burden in Systemic Light Chain Amyloidosis: Redefining Early Disease? JACC Cardiovasc Imaging. 2020 Jun;13(6):1325-1336. doi: 10.1016/j.jcmg.2020.02.025. Epub 2020 May 13.
PMID: 32417333DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sharmila Dorbala, MD
Brigham and Women's Hospital (AHA and NIH Studies)
- PRINCIPAL INVESTIGATOR
Rodney Falk, MD
Brigham and Women's Hospital (NIH Study)
- PRINCIPAL INVESTIGATOR
Ronglih Liao, PhD
Stanford School of Medicine (AHA Study)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director, Nuclear Cardiology
Study Record Dates
First Submitted
December 22, 2015
First Posted
December 29, 2015
Study Start
April 1, 2016
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2028
Last Updated
November 14, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will not share
We do not have a plan to share individual participant data with other researchers