Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease

NCT ID: NCT03325322

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-02
• Study Completion Date: 2026-12-31

Brief Summary

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.

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.

Conditions

Chronic Kidney Diseases; Diabetes Mellitus; Diabetic Nephropathies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Treatment

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

Group Type: EXPERIMENTAL

Fisetin

Intervention Type: DIETARY_SUPPLEMENT

Flavonoid family

Placebo

Placebo capsules orally for 2 consecutive days

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Placebo

Interventions

Fisetin

Flavonoid family

Intervention Type: DIETARY_SUPPLEMENT

Placebo oral capsule

Placebo

Intervention Type: DRUG

Other Intervention Names

Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

LaTonya J. Hickson

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

LaTonya J Hickson, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

References

Bian X, Snow ZK, Zinn CJ, Gowan CC, Conley SM, Bratulin AL, Elhusseiny KM, Miller J, Tchkonia T, Kirkland JL, Lerman LO, Hickson LJ. Activin A Antagonism with Follistatin Reduces Kidney Fibrosis, Injury, and Cellular Senescence-Associated Inflammation in Murine Diabetic Kidney Disease. Kidney360. 2025 Mar 28;6(8):1278-1291. doi: 10.34067/KID.0000000776.

Reference Type: DERIVED

PMID: 40152935 (View on PubMed)

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

16-010521

Identifier Type: -

Identifier Source: org_study_id