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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02848131
Recruitment Status : Recruiting
First Posted : July 28, 2016
Last Update Posted : September 17, 2018
Information provided by (Responsible Party):
LaTonya J. Hickson, Mayo Clinic

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).

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Drug: Group 2: Dasatinib Drug: Group 2: Quercetin Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents
Study Start Date : July 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
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
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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Change in Frailty index score [ Time Frame: Baseline, Day 14 ]
    Assessment by Fried and other frailty criteria at baseline and day 14.

  4. 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.

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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≥11% 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 (e.g. warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc).
  26. Subjects on antiplatelet agents (e.g. full dose aspirin which is deemed mandatory for treatment, clopidogrel, etc.). Baby aspirin, if necessary for cardioprotection, will be allowed.
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02848131

Contact: Tammie Volkman, RN 507-266-1944
Contact: Erin Wissler Gerdes 507-266-1944

United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Tammie Volkman, RN    507-266-1944   
Contact: Erin Wissler Gerdes    507-266-1944   
Principal Investigator: LaTonya Hickson, MD         
Sponsors and Collaborators
Mayo Clinic
Principal Investigator: LaTonya J Hickson, MD Mayo Clinic

Responsible Party: LaTonya J. Hickson, Principal Investigator, Mayo Clinic Identifier: NCT02848131     History of Changes
Other Study ID Numbers: 15-005843
First Posted: July 28, 2016    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs