Targeting the Pathophysiology of Sickle Cell-Related Kidney Disease Using the SGLT2 Inhibitors, Empagliflozin (EMPA-CKD)

University of Illinois

Status and phase

Not yet enrolling

Phase 2

Conditions

Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)

Albuminuria

Treatments

Drug: Empagliflozin (oral)

Study type

Interventional

Funder types

Other

Identifiers

NCT07175051

2025-0637

Details and patient eligibility

About

Sickle cell anemia (SCA) is an inherited red blood disorder. The kidneys are among the most commonly affected organ systems in SCA. The Food and Drug Administration (FDA) has approved empagliflozin as a treatment to reduce the decline of kidney function in those with kidney disease. The proposed research study aims to determine whether empagliflozin can prevent the progression of kidney dysfunction in patients with sickle cell anemia (SCA) who are at high risk of developing advanced chronic kidney disease (CKD).

Enrollment

20 estimated patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Documentation of SCA genotype (HbSS or HbSβ0-thalassemia)
Albuminuria defined by a UACR of 100 - 2,000 mg/g creatinine at the screening
Hemoglobin (Hb) ≥ 5.5 g/dL during screening
For participants taking Endari, the dose of Endari must be stable for at least one month prior to signing the ICF and with no anticipated need for dose adjustments during the study
For participants on crizanlizumab or chronic red blood cell transfusions, the therapy must have started at least 3 months prior to consent
For participants taking an angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), the dose must be stable for at least 3 months prior to signing the ICF and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator
Participants must demonstrate regular compliance with clinic visits and outpatient management
Participants, if female and of childbearing potential, will use highly effective methods of contraception from study start to 30 days after the last dose of the study drug
Participant has provided documented informed consent or assent

Exclusion criteria

Concurrent diagnosis of diabetes mellitus
Female who is breast feeding, pregnant, or unwilling to use birth control as described in the protocol
Prior hypersensitivity or intolerance to a sodium-glucose cotransporter-2 inhibitor (SGLT2i)
Active or open leg ankle ulcer
Chronic urinary tract infection
Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days prior to signing consent
Hepatic dysfunction characterized by alanine aminotransferase (ALT) >5× ULN
Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed
Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
Moderate to severe CKD (defined by an eGFR < 30 mL/min/1.73m2, on chronic dialysis, or having received a kidney transplantation)
History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy)
History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
1. Unstable angina pectoris or myocardial infarction or elective coronary intervention
2. Uncontrolled clinically significant arrhythmias
Any condition affecting drug absorption, such as major surgery involving the stomach (e.g. bariatric surgery) or small intestine (prior cholecystectomy is acceptable)
Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of agent, whichever is longer, or is currently participating in another trial of an investigational agent or medical device)
Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent
Contraindication to MRI (certain pacemakers, electronic implants, shrapnel in the eyes, or certain intracranial aneurysm clips)