Senolytic Therapy for Chronic Kidney Disease

Enrolling by invitation at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Diabetes medications

Must not be taking: Anticoagulants, Antiplatelets, Quinolones, others

Disqualifiers: Glomerulonephritis, Transplantation, Pregnancy, 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: 18

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how removing old, non-functioning cells, known as senescent cells, can improve well-being and physical abilities in people with chronic kidney disease (CKD). Participants will receive a combination of two drugs: dasatinib (a cancer treatment drug also known as Sprycel) and quercetin (a plant flavonoid), which target and remove these cells. The trial includes two groups: one receiving the treatment and one observational group for comparison. Individuals with CKD and reduced kidney function who manage diabetes with medication might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires some participants to stop or adjust certain medications. If you're on antiplatelet agents, you may need to pause them for 3 days. Also, if you're taking H2-antagonists or proton pump inhibitors, you must stop them 1 week before and 2 weeks after joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown mixed results when using dasatinib and quercetin together. Some studies suggest this combination might help with certain kidney problems. However, in cases of sudden kidney injury, it worsened some symptoms, raising concerns. Caution is necessary when using these drugs together.

As this study is in Phase 2, earlier trials have indicated it is somewhat safe for humans. However, the combination can have varying effects depending on the condition. Participants should consult the study team with any questions or concerns about safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using dasatinib and quercetin for chronic kidney disease because these compounds target the aging cells that contribute to kidney damage. Unlike traditional treatments that primarily focus on managing symptoms or slowing disease progression, dasatinib and quercetin work by clearing out senescent cells, which are older cells that have stopped dividing and can cause inflammation. This unique mechanism of action has the potential to directly address one of the underlying causes of the disease, offering a novel approach that could lead to improved kidney function and better patient outcomes.

What evidence suggests that this trial's treatments could be effective for chronic kidney disease?

This trial will evaluate the combination of dasatinib and quercetin, administered to participants in one of the study arms. Research has shown that this combination can improve kidney function in certain conditions. In animal studies, it enhanced kidney function in models of chronic kidney disease (CKD) but did not have the same effect on acute kidney injury. The treatment removes senescent cells, which are old and damaged cells that can cause problems if they remain in the body too long. By eliminating these cells, the treatment might reduce damage and enhance overall kidney health in CKD. While these results are promising, further research is needed to fully understand its effects on humans with CKD. ^{1 2 3 4 6}

Who Is on the Research Team?

LaTonya J Hickson, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults aged 40-80 with chronic kidney disease (eGFR 15-45 ml/min/1.73m2) and diabetes on medication. Excluded are those with recent substance abuse, HIV, hepatitis B/C, pregnancy, certain heart conditions or allergies to the drugs tested, among other criteria.

Inclusion Criteria

My kidney function is reduced, with an eGFR between 15-45.

I have diabetes and am on medication for it.

I am between 40 and 80 years old.

Exclusion Criteria

Your total bilirubin level is more than twice the normal limit.

I have a new cancer diagnosis that is not a non-melanoma skin cancer.

I cannot take medications by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dasatinib and quercetin to assess the effect on senescent cell burden and mesenchymal stem cell function

2 weeks

Baseline, Day 14

Follow-up

Participants are monitored for changes in kidney function and frailty index score

12 months

Month 4, Month 12

What Are the Treatments Tested in This Trial?

Interventions

• Dasatinib
• Quercetin

Trial Overview The study tests whether Dasatinib and Quercetin can reduce aging cells in patients with chronic kidney disease to improve physical function and stem cell health. Participants will be grouped to receive either drug combination.

How Is the Trial Designed?

Group I: Group 1: Observational Active Control 1 Intervention

Observational Only

Group II: Group 2: Dasatinib & Quercetin Active Control 2 Interventions

The drugs dasatinib and quercetin will be used in this arm

Dasatinib is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in European Union as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in Canada as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12195755/

Dasatinib and Quercetin Combination Increased Kidney ... In experimental diabetic nephropathy, the administration of the D&Q combination for 10 weeks improved renal function [26], as described in other models of CKD [ ...

2. preprints.org preprints.org/manuscript/202504.2175

Dasatinib and Quercetin Treatment Increased Kidney ... Conclusions: D&Q treatment was not protective in AKI-FAN, exacerbating some deleterious responses. These results suggest caution when exploring ...

3. researchgate.net researchgate.net/publication/392260686_Dasatinib_and_Quercetin_Combination_Increased_Kidney_Damage_in_Acute_Folic_Acid-Induced_Experimental_Nephropathy

Dasatinib and Quercetin Combination Increased Kidney ... Results: D&Q pretreatment did not prevent renal dysfunction in the acute phase of FAN-AKI, as determined by serum creatinine and BUN levels at ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40573218/

Dasatinib and Quercetin Combination Increased Kidney ... The senolytic drug combination of dasatinib plus quercetin (D&Q) is beneficial in some pathological conditions, including experimental CKD, but there are no ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0944711322004275

Effective dose/duration of natural flavonoid quercetin for ... Review. Effective dose/duration of natural flavonoid quercetin for treatment of diabetic nephropathy: A systematic review and meta-analysis of rodent data.

6. preprints.org preprints.org/manuscript/202504.2175/v1/download

Dasatinib and Quercetin Treatment Increased Kidney ... Conclusions: D&Q treatment was not protective in AKI-FAN, exacerbating some deleterious responses. These results suggest caution when exploring ...