Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT03325322

Collaborator

(none)

Enrollment

Location

Arms

86.9

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Diabetes Mellitus Diabetic Nephropathies	Dietary Supplement: Fisetin Drug: Placebo oral capsule	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Frailty, Inflammation, and Stem Cell Functionality in Chronic Kidney Disease

Actual Study Start Date :

Jan 2, 2018

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Fisetin 20 mg/kg/day, orally for 2 consecutive days	Dietary Supplement: Fisetin Flavonoid family
Placebo Comparator: Placebo Placebo capsules orally for 2 consecutive days	Drug: Placebo oral capsule Placebo Other Names: Placebo

Arm

Intervention/Treatment

Experimental: Treatment

Fisetin 20 mg/kg/day, orally for 2 consecutive days

Dietary Supplement: Fisetin

Flavonoid family

Placebo Comparator: Placebo

Placebo capsules orally for 2 consecutive days

Drug: Placebo oral capsule

Placebo

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

Change in inflammatory markers including C-reactive protein [14 days]
To examine the effect of study drug (compared to placebo) on markers of inflammation in skin, fat, plasma, and urine measured at baseline and day 14
Effect on Mesenchymal stem cell function including cell migration [14 days]
To examine the effect of study drug (compared to placebo) on mesenchymal stem cell function and vitality measured at baseline and day 14

Secondary Outcome Measures

Effect on measures of Frailty including Fried Criteria [4 months]
To examine the effect of study drug (compared to placebo) on markers of physical frailty (frailty phenotype).
Kidney function including estimated glomerular filtration rate [4 months]
To examine the effect of study drug (compared to placebo) on kidney function.
Kidney function including urine protein excretion rate [4 months]
To examine the effect of study drug (compared to placebo) on kidney function protein excretion
Number of participants with treatment-related adverse events including hospitalization [12 months]
To assess the safety and tolerability of study drug taken over two days (compared to placebo)

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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