Targeting the Pathophysiology of Sickle Cell-Related Kidney Disease Using the SGLT2 Inhibitors, Empagliflozin

NCT07175051 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025-0637
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0); Albuminuria

Keywords

Empa-CKD; Sickle Cell-Related Kidney Disease

Outcome Measures

Primary Outcomes (4)

• Efficacy of empagliflozin - urine biomarker: Adenosine

  Adenosine (umol/g creatinine) average values from Screening \& Visit 1 compared to average values from Visit 5 \& 6.

  From enrollment to the end of treatment at 48 weeks

• Efficacy of empagliflozin - urine biomarker: Nephrin

  Nephrin (ng/g creatinine) average values from Screening \& Visit 1 compared to average values from Visit 5 \& 6.

  From enrollment to the end of treatment at 48 weeks

• Efficacy of empagliflozin - urine biomarker: Kidney injury molecule-1

  Kidney injury molecule-1 (ng/g creatinine) average values from Screening \& Visit 1 compared to average values from Visit 5 \& 6.

  From enrollment to the end of treatment at 48 weeks

• Efficacy of empagliflozin R2* Cortical Oxygenation on kidney fMRI

  fMRI-derived R2\* average values from Visit 1 compared to the values from Visit 6.

  From enrollment to the end of treatment at 48 weeks

Secondary Outcomes (7)

• Effects of empagliflozin on UACR

  From enrollment to the end of treatment at 48 weeks

• Effects of empagliflozin on 24-hour urine protein

  From enrollment to the end of treatment at 48 weeks

• Effects of empagliflozin on measures of eGFR

  From enrollment to the end of treatment at 48 weeks

• Effects of empagliflozin on serum biomarker: suPAR

  From enrollment to the end of treatment at 48 weeks

• Effects of empagliflozin on serum biomarker: Et-1

  From enrollment to the end of treatment at 48 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Empagliflozin

Drug: Empagliflozin (oral)

Interventions

Empagliflozin (oral) DRUG

10 mg

Treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Unstable angina pectoris or myocardial infarction or elective coronary intervention
• 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)

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois Chicago, Sickle Cell Center

Chicago, Illinois, 60302, United States

Location

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MeSH Terms

Conditions

Anemia, Sickle Cell; Albuminuria

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Santosh L Saraf, MD

CONTACT

312-996-5680; ssaraf@uic.edu

Anand Srivastave, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 21, 2025
• First Posted: September 16, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)