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Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease

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ClinicalTrials.gov Identifier: NCT03325322
Recruitment Status : Recruiting
First Posted : October 30, 2017
Last Update Posted : January 5, 2018
Sponsor:
Information provided by (Responsible Party):
LaTonya J. Hickson, Mayo Clinic

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.

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 Type : Interventional  (Clinical Trial)
Estimated 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 : January 2, 2018
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
U.S. FDA Resources

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 Name: Placebo



Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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).

  2. Kidney function including estimated glomerular filtration rate [ Time Frame: 4 months ]
    To examine the effect of study drug (compared to placebo) on kidney function.

  3. 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. 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)

  5. Mesenchymal stem cells in vitro including cell migration [ Time Frame: 14 days ]
    To determine the reversibility of mesenchymal stem/stromal cell dysfunction utilizing incubation with study drug in vitro.

  6. Mesenchymal stem cells -molecular characteristics examined by second generation sequencing [ Time Frame: 14 days ]
    To examine the molecular characteristics of MSC before and after study drug by using high throughput RNA sequencing



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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 prior to and during the 2-day drug dosing. (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03325322


Contacts
Contact: Tammie Volkman, RN 507-266-1944 volkman.tammie@mayo.edu
Contact: Tamara K Evans 507-284-1004 evans.tamara@mayo.edu

Locations
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Tammie Volkman, RN    507-266-1944    volkman.tammie@mayo.edu   
Contact: Tamara K Evans    507-284-1004    evans.tamara@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: LaTonya J Hickson, MD Mayo Clinic

Responsible Party: LaTonya J. Hickson, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03325322     History of Changes
Other Study ID Numbers: 16-010521
First Posted: October 30, 2017    Key Record Dates
Last Update Posted: January 5, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by LaTonya J. Hickson, Mayo Clinic:
Frailty
Inflammation
Mesenchymal stem cell
Mesenchymal stromal cell

Additional relevant MeSH terms:
Diabetic Nephropathies
Diabetes Mellitus
Inflammation
Kidney Diseases
Renal Insufficiency, Chronic
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Urologic Diseases
Renal Insufficiency
Diabetes Complications