Empagliflozin for Sickle Cell Disease

(EMPA-CKD Trial)

Overseen By Santosh L Saraf, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Must be taking: ACE inhibitors

Must not be taking: SGLT2 inhibitors

Disqualifiers: Diabetes, Pregnancy, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether empagliflozin, a medication already approved for kidney protection, can also prevent kidney problems in people with sickle cell anemia (SCA). Sickle cell anemia is a genetic disorder that can cause serious kidney issues, among other complications. Suitable candidates have sickle cell anemia and early signs of kidney trouble, such as protein in the urine (albuminuria). Participants should not have diabetes or recent serious health issues like infections or hospital stays for sickle cell crises. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not require you to stop taking your current medications, but if you are on Endari, crizanlizumab, or an ACE inhibitor/ARB, your dose must be stable for a certain period before joining. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that empagliflozin is likely to be safe for humans?

Research has shown that empagliflozin may help with kidney problems. The FDA has already approved it to slow kidney damage in people with kidney disease. Studies have found that empagliflozin can slow the progression of chronic kidney disease (CKD), even in those without diabetes. In one study involving three patients using empagliflozin, kidney function improved.

Regarding safety, empagliflozin is generally well-tolerated. Although the study on empagliflozin for sickle cell disease (SCD) does not provide detailed safety information, its approval for other kidney conditions suggests reasonable safety. However, like any treatment, side effects can occur, so careful monitoring is important. Prospective trial participants should consult a healthcare provider about potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell anemia?

Empagliflozin is unique because it introduces a new approach to treating sickle cell disease by targeting glucose regulation, unlike current treatments that primarily focus on managing pain and preventing complications. This medication works as an SGLT2 inhibitor, which is typically used for diabetes, but it's being explored for its potential benefits in managing sickle cell disease. Researchers are excited because empagliflozin could offer a novel way to improve blood flow and reduce the incidence of painful vaso-occlusive crises, bringing a fresh perspective to sickle cell management.

What evidence suggests that empagliflozin might be an effective treatment for sickle cell anemia?

Research suggests that empagliflozin, the investigational treatment in this trial, may protect the kidneys of people with sickle cell anemia (SCA). One study showed that empagliflozin improved kidney function in SCA patients, as indicated by a better measure of kidney health called eGFR. Another study found that patients taking SGLT-2 inhibitors, like empagliflozin, had higher average hemoglobin levels, which could enhance overall health in SCA. Additionally, in animal studies of sickle cell disease, empagliflozin reduced the size of strokes, suggesting protective effects. These findings support the potential benefits of empagliflozin for those with kidney problems due to SCA. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with sickle cell anemia who have kidney issues, specifically increased protein in urine. They must be consistent with clinic visits and not have severe kidney disease or other major health problems like heart conditions, active infections, or recent participation in other trials. Women of childbearing age should commit to effective birth control during the study.

Inclusion Criteria

Participants must demonstrate regular compliance with clinic visits and outpatient management

Albuminuria defined by a UACR of 100 - 2,000 mg/g creatinine at the screening

Hemoglobin (Hb) ≥ 5.5 g/dL during screening

Exclusion Criteria

Prior hypersensitivity or intolerance to a sodium-glucose cotransporter-2 inhibitor (SGLT2i)

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)

Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive empagliflozin to assess its efficacy in preventing kidney dysfunction progression in SCA patients

48 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The trial tests if a diabetes medication called Empagliflozin can slow down worsening of kidney function in patients with sickle cell anemia at risk for chronic kidney disease. It's taken orally and has already been approved by the FDA for treating kidney decline.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Empagliflozin

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11392826/

Inhibition of sodium‐glucose cotransporter‐2 improves ... Empagliflozin treatment is also associated with reduced stroke size in SCD mice suggesting SGLT‐2 inhibitor treatment may be beneficial with ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124104983

Impact of Sglt-2 Inhibitors on Sickle Cell Disease Patients ... However, patients on SGLT-2 inhibitors had significantly higher mean Hgb levels (12.459 g/dL) compared to controls (10.358 g/dL; p<0.0001).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07175051

Targeting the Pathophysiology of Sickle Cell-Related ... The proposed research study aims to determine whether empagliflozin can prevent the progression of kidney dysfunction in patients with sickle cell anemia (SCA) ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ajh.27348

GLP‐1 agonists and SGLT‐2 inhibitors in adults with sickle ... The median duration of treatment was 21.8 (IQR, 12.0–33.7) months. The serum glucose concentrations improved from a median of 213 (IQR, 137–249) ...

5. hcplive.com hcplive.com/view/sglt2is-glp-1s-display-reno-protective-benefit-sickle-cell-disease

SGLT2is, GLP-1s Display Reno-Protective Benefit in Sickle ... Preliminary findings demonstrate an improvement in eGFR slope in nearly all patients with SCD after treatment with SGLT-2 inhibitors and GLP-1 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10371301/

Emerging Therapies and Advances in Sickle Cell Disease ... Dapagliflozin and empagliflozin have demonstrated efficacy in slowing down CKD progression, independent of diabetes diagnosis, and canagliflozin has shown ...

7. journals.lww.com journals.lww.com/jasn/fulltext/2025/10000/management_of_kidney_disease_with_sickle_cell.16.aspx

Management of Kidney Disease with Sickle Cell Disease In this study, AKI occurred in 39% of patients and was associated with a higher risk of mortality, emphasizing the importance of close monitoring of kidney ...