Transthyretin Amyloid Cardiomyopathy Clinical Trial
SGLT2 Inhibitors in Transthyretin Amyloid Cardiomyopathy
Summary
This is a single center, single arm, prospective, 12 week open label pilot trial of the sodium-glucose cotransporter 2 inhibitor (SGLT2i), empagliflozin 10 mg oral daily, in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The target population for enrollment will be subjects with ATTR-CM and either non-insulin dependent diabetes mellitus or chronic kidney disease. The primary aim will be to assess the safety and tolerability of empagliflozin 10 mg oral daily in subjects with heart failure secondary to ATTR, which remain unexplored. The accrual target is 15 subjects. Consented subjects will be evaluated for safety and tolerability of study drug, empagliflozin 10 mg oral daily, over a period of 12 weeks. Subjects will undergo a total of 6 study visits: 3 in-person and 3 telephone follow-ups.
Full Description
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underrecognized cause of heart failure among older adults, in which misfolded transthyretin (TTR) proteins build up in the muscle tissue of the heart. In 2018, a drug called tafamidis was proven to stabilize the protein and protect people from further damage, and in 2019, it was approved for use in ATTR-CM by the U.S. Food and Drug Administration (FDA). But while people with ATTR-CM are living longer, they continue to suffer from symptoms of heart failure and cardiorenal syndrome as the disease progresses. Sodium glucose co-transporter inhibitors (SGLT2i) are drugs used to treat diabetes mellitus, heart failure, and chronic kidney disease. They may also reduce systemic inflammation, and affect body composition (fat, lean mass, and total water contents) in patients with heart failure, a condition which also has significant overlap with obesity. No one has explored the safety, tolerability, and clinical effects of SGLT2i in patients with heart failure due to ATTR-CM.
Eligibility Criteria
Inclusion Criteria:
Every participant must meet all of the following inclusion criteria to be eligible for enrollment in this study:
Age ≥ 18 years old
Diagnosis of TTR cardiac amyloidosis (wild type or variant), confirmed by the presence of amyloid deposits on analysis of biopsy specimens obtained from cardiac and noncardiac sites (e.g. fat aspirate, gastrointestinal sites, salivary glands, or bone marrow), technetium-99m pyrophosphate cardiac scintigraphy, or mass spectrometry
Normal serum free light chain ratio and the absence of abnormal monoclonal band on serum and urine immunofixation
Subjects will have at least 1 of the indications below for an SGLT2i, and meet package-insert criteria for drug initiation: non-insulin dependent diabetes mellitus with hemoglobin A1c ranging from 6.5-9.9 OR chronic kidney disease (defined as an estimated glomerular filtration rate of 25-75 ml/minute/1.73 m2 of body-surface area)
On stable oral diuretics (defined as no more than a 50% increase from baseline diuretic dose established during a sustained 2 week period) within 2 weeks before enrollment
Able to understand and sign the informed consent document after the nature of the study has been fully explained
Exclusion Criteria:
The presence of any of the following excludes eligibility for enrollment in this study:
Prior liver or heart transplantation
Active malignancy or non-amyloid disease with expected survival of less than 1 year
Heart failure, in the opinion of the investigator, primarily caused by severe left-sided valve disease. Note: if valve was repaired, subject may be considered as no longer with severe valve disease
Heart failure, in the opinion of the investigator, primarily caused by ischemic heart disease
Ventricular assist device or anticipated within the next 6 months
Pacemaker or implantable cardioverter defibrillator incompatible with magnetic resonance technology
Absolute contraindication for quantitative magnetic resonance (e.g. aneurysmal clips, metal objects)
Impairment from stroke, injury or other medical disorder that precludes participation in the study
Myocardial infarction, cardiovascular surgery, stroke or transient ischemic attack within the prior 90 days
Disabling dementia or other mental or behavioral disease
Enrollment in a clinical trial not approved for co-enrollment
Expected use of continuous intravenous inotropic therapy in the next 6 months
High risk for non-adherence as determined by screening evaluation
Inability or unwillingness to comply with the study requirements
Chronic kidney disease with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 or end-stage renal disease
Current or prior SGLT2i use
Type 1 diabetes mellitus or insulin-dependent diabetes mellitus
N-terminal (NT)-pro hormone BNP (NT-proBNP) < 300 pg/mL or < 900 pg/mL if concomitant diagnosis of atrial fibrillation
History of ketoacidosis
History of complex urinary tract or genital infections
History of kidney stone
Systolic blood pressure < 90 mmHg and symptomatic hypotension
Systolic blood pressure ≥ 180 mmg Hg
Chronic obstructive pulmonary disease
Major surgery in the 90 days before or after screening
Chronic alcohol or drug abuse
Nursing home resident
Other reason that would make the subject inappropriate for entry into this study
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There is 1 Location for this study
New York New York, 10032, United States
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