Health TrialsbyHealthPanel

Molecular Imaging of Primary Amyloid Cardiomyopathy

ConditionsAmyloidosis, PrimaryCardiomyopathy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-99
SponsorBrigham and Women's Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • F-18 florbetapir/C-11 acetate PET

    Radiation

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

  • MRI

    Device

    Cardiac MRI with gadolinium contrast.

  • N-13 ammonia PET

    Radiation

    N-13 ammonia PET scan following supine bicycle stress.

Treatment groups

171 Participants
are divided into 5 treatment groups
Group A: Active AL cardiac amyloidosisExperimental treatment 3 interventions
Group B: Remission AL cardiac amyloidosisActive comparator 2 interventions
Group C: Active AL Pre-CMPExperimental treatment 2 interventions
Group D: Multiple Myeloma ControlsNo intervention 0 interventions
Group E: Heart FailureExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Time frame
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

Time frame
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

Time frame
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

Time frame
Baseline, 6 and 12 months

Secondary outcomes

1

Change in Myocardial energy efficiency from baseline to 6 months

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

Time frame
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

Time frame
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.

Time frame
Baseline

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Brigham and Women's Hospital

Lead sponsor

National Institutes of Health (NIH)

Collaborator

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

American Heart Association

Collaborator

Source ClinicalTrials.gov
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