Senescence in Chronic Kidney Disease

Overview

About this study

To compare the effect of senolytic drugs on cellular senescence, physical ability or frailty, and adipose tissue-derived MSC functionality in patients with chronic kidney disease.

Primary Objectives:
To assess the efficacy of a single 3-day treatment regimen with dasatinib and quercetin (senolytic drugs) on clearing senescent adipose-derived MSC in patients with CKD.

To assess the efficacy of a single 3-day treatment regimen with dasatinib and quercetin (senolytic drugs) on improving adipose-derived MSC functionality in patients with CKD.

Secondary Objective:
To assess the short-term effect of a single 3-day treatment regimen with dasatinib and quercetin (senolytic drugs) on frailty index score in patients with CKD.

To assess the short-term effect of a single 3-day treatment regimen with dasatinib and quercetin (senolytic drugs) on kidney function in patients with CKD.

To assess the safety and tolerability of a single 3-day treatment regimen with dasatinib 100 mg daily and quercetin 1000 mg total daily in subjects with CKD.

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. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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 the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Elizabeth Lorenz, M.D.

Open for enrollment

Contact information:

Department of Medicine - Clinical Research Office

(507) 266-1944

RSTDOMCTU@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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