Senescence in Chronic Kidney Disease

• Status: Enrolling by invitation
• Trial end date: 2022-06-02
• Target enrollment: 0
• Participant gender: All

Summary

The study goal is to assess the effect of senescent cell clearance on senescence burden, physical ability or frailty, and adipose tissue-derived mesenchymal stem cell (MSC) functionality in patients with chronic kidney disease (CKD).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Treatments: Dasatinib; Quercetin

Criteria

Inclusion Criteria:

1. Age 40-80 years

2. Chronic kidney disease estimated glomerular filtration rate (eGFR) 15-45 ml/min/1.73m2

3. Diabetes mellitus and taking diabetes medications

Exclusion Criteria:

1. Concomitant glomerulonephritis,

2. Nephrotic syndrome,

3. Solid organ transplantation,

4. Autosomal dominant or recessive polycystic kidney disease,

5. Known renovascular disease,

6. Pregnancy,

7. Active immunosuppression therapy,

8. Hemoglobin A1c≥10% at screening,

9. History of active substance abuse (including alcohol) within the past 2 years,

10. Current alcohol abuse (>3 alcoholic beverages/day or >21 per week),

11. Body weight >150 kg or body mass index>50

12. Human immunodeficiency virus infection

13. Active hepatitis B or C infection

14. Tyrosine kinase inhibitor therapy

15. Known hypersensitivity or allergy to dasatinib or quercetin

16. Inability to give informed consent

17. Uncontrolled systemic lupus erythematosus

18. Uncontrolled pleural/pericardial effusions or ascites

19. New invasive cancer except non-melanoma skin cancers

20. Invasive fungal or viral infection

21. Inability to tolerate oral medications

22. Total bilirubin>2x upper limit of normal

23. Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic.

24. Subjects on strong inhibitors of CYP3A4.

25. Subjects on therapeutic doses of anticoagulants (Warfarin (Coumadin);Rivaroxaban (Xarleto); Apixaban (Eliquis); Dabigatran (Pradaxa, Prazaxa) or Other).

26. Subjects on antiplatelet agents ((Clopidogrel (Plavix); Dipyridamole + Asprin (Aggrenox); Ticagrelor (Brilinta); Prasugrel (Effient); Ticlopidine (Ticlid) or Other) who are unable or unwilling to reduce or hold therapy prior to and during the 3-day drug dosing. Subjects may continue their previous regimen on day 4.

27. Subjects on quinolone antibiotic therapy for treatment or for prevention of infections within 10 days

28. Subjects taking H2-antagonists or proton pump inhibitors and unwilling to discontinue therapy 1 week prior and 2 weeks following enrollment.

29. Corrected QT interval (QTc)>450 msec

30. Presence of any condition that the Investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial.