SGLT2 Inhibitors in ATTR

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Brief Title

SGLT2 Inhibitors in ATTR

Official Title

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors in Transthyretin Amyloid (ATTR) Cardiomyopathy

Brief 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.
    

Detailed 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.
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Serious Adverse Event (SAE) Rate

Secondary Outcome

 Mean Change in Daily Diuretic Dose

Condition

Transthyretin Amyloid Cardiomyopathy

Intervention

Empagliflozin

Study Arms / Comparison Groups

 Study Drug Arm
Description:  Subjects will take empagliflozin 10 mg oral daily for 12 weeks.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

15

Start Date

March 14, 2022

Completion Date

March 2023

Primary Completion Date

March 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Every participant must meet all of the following inclusion criteria to be eligible for
             enrollment in this study:

               1. Age ≥ 18 years old

               2. 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

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

               4. 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)

               5. 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

               6. 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:

               1. Prior liver or heart transplantation

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

               3. 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

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

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

               6. Pacemaker or implantable cardioverter defibrillator incompatible with magnetic
                  resonance technology

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

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

               9. Myocardial infarction, cardiovascular surgery, stroke or transient ischemic
                  attack 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) <15
                  mL/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 if
                  concomitant 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 this study
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mathew Maurer, MD, 646-906-2255, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT05233163

Organization ID

AAAT9709


Responsible Party

Principal Investigator

Study Sponsor

Columbia University


Study Sponsor

Mathew Maurer, MD, Principal Investigator, Columbia University


Verification Date

March 2022