Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease

April 3, 2023 updated by: LaTonya J. Hickson, Mayo Clinic

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

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.

Study Overview

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo capsules orally for 2 consecutive days
Placebo
Other Names:
  • Placebo
Experimental: Treatment
Fisetin 20 mg/kg/day, orally for 2 consecutive days
Flavonoid family

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in inflammatory markers including C-reactive protein
Time Frame: 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
14 days
Effect on Mesenchymal stem cell function including cell migration
Time Frame: 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
14 days

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: LaTonya J Hickson, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 2, 2018

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

October 12, 2017

First Submitted That Met QC Criteria

October 24, 2017

First Posted (Actual)

October 30, 2017

Study Record Updates

Last Update Posted (Actual)

April 5, 2023

Last Update Submitted That Met QC Criteria

April 3, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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