Senescence in Chronic Kidney Disease

Chronic Kidney Disease Clinical Trial

Official title:

Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02848131
• Other study ID #: 15-005843
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: July 2016
• Est. completion date: April 2025

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

The proposed studies will examine cellular senescence and the effect of senolytic therapy on senescent cell burden, frailty, and adipose-derived mesenchymal stem cell function in individuals with diabetic chronic kidney disease.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 30
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Group 2: Dasatinib
Dasatinib - take one 100 mg tablet by mouth once daily for 3 consecutive days.
• Group 2: Quercetin
Quercetin - take four 250 mg capsules daily (total 1000 mg daily) for 3 consecutive days.

Locations

Country	Name	City	State
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in proportion of senescent cells (representing the total senescent cell burden) present	Assessment of senescence markers in skin, fat, and/or blood at baseline and day 14.	Baseline, Day 14
Secondary	Change in proportion of senescent mesenchymal stem cells present	Assessment of senescence markers in mesenchymal stem cells at baseline and day 14.	Baseline, Day 14
Secondary	Change in mesenchymal stem cell function	Assessment of functional studies in mesenchymal stem cells at baseline and day 14. Number of subjects with change in stem cell function related to treatment.	Baseline, Day 14
Secondary	Change in Frailty index score	Assessment by Fried and other frailty criteria at baseline and day 14.	Baseline, Day 14
Secondary	Change in kidney function	Assessment by estimated and measured glomerular filtration rate at baseline, day 14, month 4, and month 12.	Baseline, Day 14, Month 4, Month 12