Senescence in Chronic Kidney Disease

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 15-005843
    NCT ID: NCT02848131
    Sponsor Protocol Number: 15-005843

About this study

Trials applying stem cells for the treatment of diabetic kidney disease (DKD) will soon be under way.  Autologous (from the patient) over allogeneic transplantation is the preferred option.  However, success with cellular therapy in DKD patients may be limited by a frailty phenotype and “unhealthy” stem cells due to cellular senescence.  The purpose of this study is to examine the effect of two drugs on mesenchymal stem cells, physical body function (or frailty), kidney function, and total clearance of senescent cells. Information from these investigations will help design preconditioning protocols for clinical trials applying stem cells for the treatment of DKD. 

At present, we are enrolling participants with DKD, aged 40-80 years, and eGFR 15-45 mL/min/1.73m2. After screening and enrollment, study participants will be randomized to either the treatment or non-treatment (placebo) arm.  Participants in the treatment arm will take 2 drugs for 3 days.  For all participants, an olive-sized sample of subcutaneous fat will be taken from the abdomen for MSC isolation and repeated at day 14.  A frailty assessment along with blood and urine laboratory testing will be done at a total of 3 study visits (enrollment, day 14, and month 4).  Mail-out labs will be accepted for month 12 follow-up. 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Age 40-80 years old.
  • Chronic kidney disease estimated glomerular filtration rate (eGFR)15-45 ml/min/1.73m2.
  • Diabetes mellitus and taking diabetes medications.

Exclusion Criteria:

  • Concomitant glomerulonephritis.
  • Nephrotic syndrome.
  • Solid organ transplantation.
  • Autosomal dominant or recessive polycystic kidney disease.
  • Known  renovascular disease.
  • Pregnancy.
  • Active immunosuppression therapy.
  • Hemoglobin A1c ≥ 10% at screening.
  • History of active substance abuse (including alcohol) within the past 2 years.
  • Current alcohol abuse (> 3 alcoholic beverages/day or > 21 per week).
  • Body weight > 150 kg or body mass index (BMI) > 50.
  • Human immunodeficiency virus infection.
  • Active hepatitis B or C infection.
  • Tyrosine kinase inhibitor therapy.
  • Known hypersensitivity or allergy to dasatinib or quercetin.
  • Inability to give informed consent.
  • Uncontrolled systemic lupus erythematosus.
  • Uncontrolled pleural/pericardial effusions or ascites.
  • New invasive cancer except non-melanoma skin cancers.
  • Invasive fungal or viral infection.
  • Inability to tolerate oral medications.
  • Total bilirubin > 2x upper limit of normal.
  • 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). antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels aretherapeutic.
  • Strong inhibitors of CYP3A4.
  • Subjects on therapeutic doses of anticoagulants (Warfarin (Coumadin);Rivaroxaban (Xarleto);Apixaban (Eliquis); Dabigatran (Pradaxa, Prazaxa) or Other).
  • Subjects on antiplatelet agents ((Clopidogrel (Plavix); Dipyridamole + Asprin (Aggrenox); Ticagrelor (Brilinta); Prasugrel (Effient); Ticlopidine (Ticlid) orOther) who are unable or unwilling to reduce or hold therapy prior to and during the 2-day drug dosing. Subjects may continue their previous regimen on day 3.
  • Subjects on quinolone antibiotic therapy for treatment or for prevention ofinfections within 10 days.
  • Subjects taking H2-antagonists or proton pump inhibitors and unwilling to discontinue therapy for 1 week before and 2 weeks following enrollment.
  • QTc > 450msec.
  • 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.
  • *Active immunosuppression therapy may include common systemic drugs such as tacrolimus, sirolimus, cyclosporin, rituximab (or other monoclonal antibodies), mycophenolate mofetil. Most potential subjects on these medication therapies will be identified through the exclusion criteria outlined above.
  • Involvement of special vulnerable populations:
    • We will not involve special vulnerable populations, such as fetuses, neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

LaTonya Hickson, M.D.

Open for enrollment

Contact information:

Department of Medicine – Clinical Research Office

(507) 266-1944

RSTDOMCRO@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20200698

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