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Senescence in Chronic Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02848131
Recruitment Status : Enrolling by invitation
First Posted : July 28, 2016
Last Update Posted : July 22, 2020
Information provided by (Responsible Party):
LaTonya J. Hickson, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE March 22, 2016
First Posted Date  ICMJE July 28, 2016
Last Update Posted Date July 22, 2020
Actual Study Start Date  ICMJE July 2016
Estimated Primary Completion Date December 2, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
Change in proportion of senescent cells (representing the total senescent cell burden) present [ Time Frame: Baseline, Day 14 ]
Assessment of senescence markers in skin, fat, and/or blood at baseline and day 14.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
  • Change in proportion of senescent mesenchymal stem cells present [ Time Frame: Baseline, Day 14 ]
    Assessment of senescence markers in mesenchymal stem cells at baseline and day 14.
  • Change in mesenchymal stem cell function [ Time Frame: Baseline, Day 14 ]
    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.
  • Change in Frailty index score [ Time Frame: Baseline, Day 14 ]
    Assessment by Fried and other frailty criteria at baseline and day 14.
  • Change in kidney function [ Time Frame: Baseline, Day 14, Month 4, Month 12 ]
    Assessment by estimated and measured glomerular filtration rate at baseline, day 14, month 4, and month 12.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Senescence in Chronic Kidney Disease
Official Title  ICMJE Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents
Brief 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).
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Kidney Disease
Intervention  ICMJE
  • Drug: Group 2: Dasatinib
    Dasatinib - take one 100 mg tablet by mouth once daily for 3 consecutive days.
    Other Name: Sprycel
  • Drug: Group 2: Quercetin
    Quercetin - take four 250 mg capsules daily (total 1000 mg daily) for 3 consecutive days.
Study Arms  ICMJE
  • No Intervention: Group 1: Observational
    Observational Only
  • Active Comparator: Group 2: Dasatinib & Quercetin
    The drugs dasatinib and quercetin will be used in this arm
    • Drug: Group 2: Dasatinib
    • Drug: Group 2: Quercetin
Publications * Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, Herrmann SM, Jensen MD, Jia Q, Jordan KL, Kellogg TA, Khosla S, Koerber DM, Lagnado AB, Lawson DK, LeBrasseur NK, Lerman LO, McDonald KM, McKenzie TJ, Passos JF, Pignolo RJ, Pirtskhalava T, Saadiq IM, Schaefer KK, Textor SC, Victorelli SG, Volkman TL, Xue A, Wentworth MA, Wissler Gerdes EO, Zhu Y, Tchkonia T, Kirkland JL. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019 Sep;47:446-456. doi: 10.1016/j.ebiom.2019.08.069. Epub 2019 Sep 18. Erratum in: EBioMedicine. 2020 Feb;52:102595.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Actual Enrollment  ICMJE
 (submitted: June 4, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2016)
Estimated Study Completion Date  ICMJE June 2, 2021
Estimated Primary Completion Date December 2, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02848131
Other Study ID Numbers  ICMJE 15-005843
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party LaTonya J. Hickson, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: LaTonya J Hickson, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP