Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0), Albuminuria
Conditions
Keywords
Empa-CKD, Sickle Cell-Related Kidney Disease
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).
Interventions
10 mg
Sponsors
University of Illinois at Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of empagliflozin - urine biomarker: Adenosine | From enrollment to the end of treatment at 48 weeks | Adenosine (umol/g creatinine) average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
| Efficacy of empagliflozin - urine biomarker: Nephrin | From enrollment to the end of treatment at 48 weeks | Nephrin (ng/g creatinine) average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
| Efficacy of empagliflozin - urine biomarker: Kidney injury molecule-1 | From enrollment to the end of treatment at 48 weeks | Kidney injury molecule-1 (ng/g creatinine) average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
| Efficacy of empagliflozin R2* Cortical Oxygenation on kidney fMRI | From enrollment to the end of treatment at 48 weeks | fMRI-derived R2\* average values from Visit 1 compared to the values from Visit 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of empagliflozin on serum biomarker: Et-1 | From enrollment to the end of treatment at 48 weeks | ET-1 pg/mL average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
| Effects of empagliflozin on UACR | From enrollment to the end of treatment at 48 weeks | Change in UACR (mg/g creatinine) average values from Screening & Visit 1 compared to average values from Visit 5 & 6 |
| Effects of empagliflozin on serum biomarker: sFLTI-1 | From enrollment to the end of treatment at 48 weeks | sFLTI-1 ng/L average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
| Effects of empagliflozin on serum biomarker: VCAM-1 | From enrollment to the end of treatment at 48 weeks | VCAM-1 ng/mL average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
| Effects of empagliflozin on 24-hour urine protein | From enrollment to the end of treatment at 48 weeks | 24-hour urine protein (g/24 hours) average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
| Effects of empagliflozin on measures of eGFR | From enrollment to the end of treatment at 48 weeks | eGFR calculated by race-free serum creatinine and cystatin C-based equations (mL/min/1.73m2), average values from Screening & Visit 1 compared to average values from Visit 5 & 6 |
| Effects of empagliflozin on serum biomarker: suPAR | From enrollment to the end of treatment at 48 weeks | suPAR pg/mL average values from Screening & Visit 1 compared to average values from Visit 5 & 6. |
Countries
United States
Contacts
Primary ContactSantosh L Saraf, MD
Backup ContactAnand Srivastave, MD
Outcome results
None listed