Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease

Mayo Clinic

Status and phase

Suspended

Phase 2

Conditions

Chronic Kidney Diseases

Diabetic Nephropathies

Diabetes Mellitus

Treatments

Dietary Supplement: Fisetin

Drug: Placebo oral capsule

Study type

Interventional

Funder types

Other

Identifiers

NCT03325322

16-010521

Details and patient eligibility

About

Full description

The proposed studies will examine the effect of fisetin on adipose tissue-derived mesenchymal stem/stromal cell function, kidney function, markers of inflammation, and physical function in individuals with advanced chronic kidney disease, particularly diabetic kidney disease. This study will involve a single 2-day oral treatment regimen with fisetin or placebo. Study subjects will be randomized 2:1 to study drug or placebo. Study visits will consist of blood, urine, and abdominal wall skin and subcutaneous fat samplings in addition to testing of physical strength at given time points. Subjects will be followed for a total of 12 months.

Enrollment

30 estimated patients

Sex

All

Ages

40 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 40-80 years
Chronic kidney disease estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73m2
For the diabetic kidney disease (DKD) subgroup: Diabetes mellitus (on medication)

Exclusion criteria

Hemoglobin A1c>11% at screening for the DKD subgroup
Body weight >150 kg or body mass index>50
Pregnancy
Active glomerulonephritis treated with immunosuppressive therapy
Solid organ transplantation (eg. kidney, pancreas, liver, lung, heart)
Active immunosuppression therapy
History of active substance abuse (including alcohol) within the past 2 years,
Current alcohol abuse (>3 alcoholic beverages/day or >21 per week),
Human immunodeficiency virus infection
Active hepatitis B or C infection
Total bilirubin >2x upper limit of normal
Uncontrolled psychiatric disorder
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
Known hypersensitivity or allergy to Fisetin
Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6CYP2C9, CYP2C19, CYP1A2, Other (OATP1B1) (Unless willing and able to stop or modify the dosing of the drug) or strong inhibitors or inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus).
Tyrosine kinase inhibitor therapy
Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc.).
Subjects on full-dose 325 mg aspirin or other anti-platelet agents (eg. clopidogrel) daily 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.
Baby aspirin (81 mg), if necessary for cardioprotection, will be allowed but encouraged to hold.
Subjects taking proton pump inhibitors who are unable or unwilling to reduce or hold therapy 2 days prior to and during the 2-day drug dosing. Subjects taking H2-antagonists and unwilling to discontinue therapy for 2 weeks before and one week following enrollment. (See Appendix 4)
Subjects taking glimepiride or glyburide for diabetes therapy who are unable or unwilling to reduce or hold therapy prior to and during the 2-day drug dosing.
Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin, erythromycin), Antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir), Rifampin
Corrected QT interval (QTc) >450 msec
Tobacco use (smoking or chewing; Unless subject willing to reduce use by 50% prior to and during the study) - see Behavioral Modification information below.
Inability to give informed consent
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