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Amyloidosis, PrimaryMICANCT02641145

Molecular Imaging of Primary Amyloid Cardiomyopathy

A study testing F-18 florbetapir/C-11 acetate PET, MRI and N-13 ammonia PET in people with Amyloidosis, Primary and Cardiomyopathy, run by Brigham and Women's Hospital at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Amyloidosis, Primary, Cardiomyopathy
What is being tested?
F-18 florbetapir/C-11 acetate PET, MRI and N-13 ammonia PET
Could I receive a placebo?
No, everyone receives an active treatment
How many people
171 participants
Where
1 siteUnited States
Study dates
1 Apr 2016to 31 Dec 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Additional inclusion criteria for the Remission AL-CMP: Hematological response defined as complete hematological remission or very good partial response-differential free light chain (dFLC)<40 mg/dL for > 1 year prior to enrollment
Show all 11Show fewer
  • Additional inclusion criteria for the Active AL-CMP - exercise: Ability to perform supine bicycle exercise. Enrollment to this arm will stop after 36 subjects complete baseline and 6 months studies.
  • Additional inclusion criteria for the Active AL Pre-CMP - Normal left ventricular wall thickness (≤ 12 mm) and normal LVEF (≥55%) on echocardiography within 3 months or increased wall thickness with normal cardiac biomarker levels: not meeting above definition.
  • Additional inclusion criteria for Control Multiple Myeloma subjects: diagnosis of multiple myeloma without concomitant amyloidosis by standard criteria
  • Additional inclusion criteria for Control Heart Failure subjects: diagnosis of heart failure without amyloidosis by standard criteria
  • Additional inclusion criteria for the active AL-CMP: Abnormal TnT 5th generation levels (>9 ng/L: Female, >14 ng/L: Male) or abnormal age appropriate N terminal pro-brain natriuretic peptide, NT-proBNP (abnormal values: <50 years: >450 pg/ml; 50-75 years:>900 pg/ml; >75 years: >1800 pg/ml)

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.
  • Additional exclusion criteria for the active AL-CMP subjects: Subjects unable to return to BWH for 6 and 12 month clinical evaluation
  • Additional exclusion criteria for active AL-CMP-exercise subjects: Inability to exercise or return to BWH for C-11 acetate PET/CT at baseline and 6 month clinical evaluations.
  • Additional exclusion criteria for active AL Pre-CMP- Inability to return to BWH 12 month clinical evaluation.
  • Additional exclusion criteria for microbiota study: Documented hypertrophic cardiomyopathy, HIV or chronic viral hepatitis, documented inflammatory bowel disease, systemic antibiotics, antivirals, antifungals or antiparasitic agents within 6 months, unable to mail the stool sample in a timely manner, bowel surgery, colon cancer, received chemotherapy, and pregnancy.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sharmila Dorbala, MD, MPH contact

617-732-6290

sdorbala@partners.org

United States1 site, 1 recruiting

  • Brigham and Womens' Hospital

    Boston, Massachusetts, 02421

    Sharmila Dorbala, sdorbala@bwh.harvard.edu

    Sharmila Dorbala, MBBS

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

Primary light chain amyloidosis (AL) is the most common systemic amyloidosis, resulting from a plasma cell dyscrasia, a hematological malignancy. It causes a restrictive cardiomyopathy (AL-CMP) in over 70% of individuals. AL-CMP is as lethal as stage 4 lung cancer and more lethal than any other form of restrictive heart disease; if untreated, the mortality rate is 50% within 18 months. Moreover, myocardial dysfunction, the hallmark of AL-CMP, significantly increases early treatment related mortality, predominantly cardiovascular death, and is a powerful predictor of poor long-term survival. Two potentially treatable mechanisms underlie myocardial dysfunction-mechanical effects of amyloid and toxic effects from circulating light chain/ amyloid interactions-and predispose to heart failure, arrhythmias, and sudden death in individuals with AL-CMP. Until now, efforts to determine the mechanisms of AL-CMP have been hampered by a lack of animal models and the limitations of noninvasive techniques to directly image myocardial amyloid. A recent breakthrough, 18F-florbetapir PET/CT, has provided for the first time specific and quantitative imaging of myocardial amyloid including toxic amyloid protofibrils. Furthermore, we propose to investigate three pre-clinically proven pathways of light chain toxicity in humans-myocardial oxidative metabolism, oxidative stress, and coronary microvascular function. Our central hypotheses are that myocardial 18F-florbetapir retention is a biomarker for aggressiveness of AL-CMP and that effective chemotherapy will, by reducing circulating light chains, decrease aggressiveness of AL-CMP and improve oxidative stress, myocardial oxidative metabolism, microvascular function and contractile function, prior to an improvement in myocardial amyloid content. In Aim 1, we will quantify myocardial 18F-florbetapir retention as a marker of aggressive myocardial disease in individuals with AL-CMP and active plasma cell dyscrasia compared to control individuals with AL-CMP and long-term hematological remission. In Aim 2, we propose, using advanced imaging, to assess the effects of light chain reduction due to chemotherapy on myocardial structure, function, and metabolism and define the time course of these changes. Serial ECV and strain imaging by CMR, serum F2-isoprostanes and peroxynitrite levels, myocardial oxidative metabolism (Kmono) and coronary flow reserve by 11C-acetate PET, and 18F-florbetapir imaging will not only intricately characterize the myocardial substrate in AL-CMP, but also identify changes in response to therapy. The proposed studies offer the potential to transform our current understanding of AL-CMP as a restrictive heart disease caused by passive amyloid-related architectural damage to that of a more complex disorder resulting from both passive and aggressive factors. The results of these studies may form the foundation for drug discovery programs to prevent and cure AL-CMP.

Interactions of environmental factors, immunity, and host-related factors likely trigger AL-amyloidosis, but have not yet been explored. Changes in metal ions and gut microbiota may be causal, representing the integrated effects of all these factors, or may be the downstream effect of systemic amyloid deposition in the organ systems. A plethora of recent literature strongly support the role of microbiota in the pathogenesis of several diseases, suggesting that gut microbiota changes with age, influences heart failure (HF) outcomes, and plays a role in the formation of β-amyloid deposits in Alzheimer's disease. Importantly, alterations in lifestyle, diet, prebiotics, probiotics, or phenols and gut microbiota may represent therapeutic and preventative strategies in amyloid disease, but it has not been explored in AL-amyloidosis. We propose to study the role of salivary and gut microbiome in AL amyloidosis.

Being tested
F-18 florbetapir/C-11 acetate PET, MRI, N-13 ammonia PET
Keywords
amyloidosis, F-18 florbetapir, Positron emission tomography, cardiac magnetic resonance imaging
Medical subject headings
Immunoglobulin Light-chain Amyloidosis, Cardiomyopathies, Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • F-18 florbetapir/C-11 acetate PETRadiation

    F-18 florbetapir PET scan, C-11 acetate PET scan

  • MRIDevice

    Cardiac MRI with gadolinium contrast.

  • N-13 ammonia PETRadiation

    N-13 ammonia PET scan following supine bicycle stress.

Study groups in NCT02641145
Study groupRoleWhat they receive
Active AL cardiac amyloidosisExperimental75 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.
Receives: Radiation: F-18 florbetapir/C-11 acetate PET; Device: MRI; Radiation: N-13 ammonia PET
Remission AL cardiac amyloidosisActive 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.
Receives: Radiation: F-18 florbetapir/C-11 acetate PET; Device: MRI
Active AL Pre-CMPExperimental36 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.
Receives: Radiation: F-18 florbetapir/C-11 acetate PET; Device: MRI
Multiple Myeloma ControlsNo intervention25 individuals with diagnosis of multiple myeloma without concomitant amyloidosis by standard criteria will undergo urine and blood testing only.
Heart FailureExperimental10 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..
Receives: Radiation: F-18 florbetapir/C-11 acetate PET; Device: MRI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline, 6 and 12 months

  2. Change in Serum oxidative stress markers from baseline to 6 months and 12 months

    serum F-2 isoprostane and peroxynitrite levels

    Measured: Baseline, 6 and 12 months

  3. 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

    Measured: Baseline and 6 months

  4. 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

    Measured: Baseline, 6 and 12 months

Secondary outcomes (3)

  1. Change in Myocardial energy efficiency from baseline to 6 months

    Myocardial energy efficiency, Kmono reserve, will be determined by C-11 acetate PET

    Measured: Baseline and 6 months

  2. Light Chain Toxicity

    Study subject urine light chain's will be extracted and infused into zebrafish and isolated cardiomyocytes to study light chain toxicity

    Measured: Baseline

  3. Understand the role of gut microbiota and heavy metals in the pathogenesis of AL Amyloidosis

    This will be tested using machine learning methods with 16S rRNA sequencing of salivary and stool samples in a 40-patient cohort with AL-amyloidosis compared to healthy controls from the NIH funded human microbiome project (HMP).This will also be used to test if the gut microbiome affects amyloid formation using a transgenic mouse model of AL amyloidosis that expresses the human LC in the gut and develops amyloid in the stomach.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2015 (estimated)
  2. Study start1 Apr 2016
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
171 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02641145
Sponsor's protocol ID
2015P002477
Other IDs
1R01HL130563-01A1
Acronym
MICA
Status last verified
Nov 2025
First submitted
22 Dec 2015
Last updated
14 Nov 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No: We do not have a plan to share individual participant data with other researchers

Publications

  • 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.

    PubMed 40938234

  • Clerc 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.

    PubMed 39001736

  • Katznelson 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.

    PubMed 38873265

  • Cuddy 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.

    PubMed 34922860

  • Cuddy 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.

    PubMed 32417333

Questions about this trial

What is this clinical trial studying?

A study testing F-18 florbetapir/C-11 acetate PET, MRI and N-13 ammonia PET in people with Amyloidosis, Primary and Cardiomyopathy, run by Brigham and Women's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sharmila Dorbala, MD, MPH (617-732-6290, sdorbala@partners.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in F-18 florbetapir myocardial retention index from baseline to 6 months and 12 months (time frame: Baseline, 6 and 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02641145, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2025.

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