SGLT2 Inhibitors in Transthyretin Amyloid Cardiomyopathy

Last updated: July 10, 2024
Sponsor: Columbia University
Overall Status: Completed

Phase

4

Condition

Amyloidosis

Circulation Disorders

Treatment

Empagliflozin

Clinical Study ID

NCT05233163
AAAT9709
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Every participant must meet all of the following inclusion criteria to be eligiblefor enrollment in this study:
  1. Age ≥ 18 years old

  2. Diagnosis of TTR cardiac amyloidosis (wild type or variant), confirmed by thepresence of amyloid deposits on analysis of biopsy specimens obtained fromcardiac and noncardiac sites (e.g. fat aspirate, gastrointestinal sites,salivary glands, or bone marrow), technetium-99m pyrophosphate cardiacscintigraphy, or mass spectrometry

  3. Normal serum free light chain ratio and the absence of abnormal monoclonal bandon serum and urine immunofixation

  4. Subjects will have at least 1 of the indications below for an SGLT2i, and meetpackage-insert criteria for drug initiation: non-insulin dependent diabetesmellitus 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 m2of body-surface area)

  5. On stable oral diuretics (defined as no more than a 50% increase from baselinediuretic dose established during a sustained 2 week period) within 2 weeksbefore enrollment

  6. Able to understand and sign the informed consent document after the nature ofthe study has been fully explained

Exclusion

Exclusion Criteria:

  • The presence of any of the following excludes eligibility for enrollment in thisstudy:
  1. Prior liver or heart transplantation

  2. Active malignancy or non-amyloid disease with expected survival of less than 1year

  3. Heart failure, in the opinion of the investigator, primarily caused by severeleft-sided valve disease. Note: if valve was repaired, subject may beconsidered as no longer with severe valve disease

  4. Heart failure, in the opinion of the investigator, primarily caused by ischemicheart disease

  5. Ventricular assist device or anticipated within the next 6 months

  6. Pacemaker or implantable cardioverter defibrillator incompatible with magneticresonance technology

  7. Absolute contraindication for quantitative magnetic resonance (e.g. aneurysmalclips, metal objects)

  8. Impairment from stroke, injury or other medical disorder that precludesparticipation in the study

  9. Myocardial infarction, cardiovascular surgery, stroke or transient ischemicattack within the prior 90 days

  10. Disabling dementia or other mental or behavioral disease

  11. Enrollment in a clinical trial not approved for co-enrollment

  12. Expected use of continuous intravenous inotropic therapy in the next 6 months

  13. High risk for non-adherence as determined by screening evaluation

  14. Inability or unwillingness to comply with the study requirements

  15. Chronic kidney disease with estimated glomerular filtration rate (eGFR) <15mL/min/1.73 m2 or end-stage renal disease

  16. Current or prior SGLT2i use

  17. Type 1 diabetes mellitus or insulin-dependent diabetes mellitus

  18. N-terminal (NT)-pro hormone BNP (NT-proBNP) < 300 pg/mL or < 900 pg/mL ifconcomitant diagnosis of atrial fibrillation

  19. History of ketoacidosis

  20. History of complex urinary tract or genital infections

  21. History of kidney stone

  22. Systolic blood pressure < 90 mmHg and symptomatic hypotension

  23. Systolic blood pressure ≥ 180 mmg Hg

  24. Chronic obstructive pulmonary disease

  25. Major surgery in the 90 days before or after screening

  26. Chronic alcohol or drug abuse

  27. Nursing home resident

  28. Other reason that would make the subject inappropriate for entry into thisstudy

Study Design

Total Participants: 15
Treatment Group(s): 1
Primary Treatment: Empagliflozin
Phase: 4
Study Start date:
March 14, 2022
Estimated Completion Date:
May 01, 2023

Study 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.

Connect with a study center

  • Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

    New York, New York 10032
    United States

    Site Not Available

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