Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease

Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03325322
• Other study ID #: 16-010521
• Status: Suspended
• Phase: Phase 2
• Start date: January 2, 2018
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 30
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Diabetes Mellitus
• Diabetic Nephropathies
• Inflammation
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Fisetin
Flavonoid family

Drug:
• Placebo oral capsule
Placebo

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in inflammatory markers including C-reactive protein	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
Primary	Effect on Mesenchymal stem cell function including cell migration	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	Effect on measures of Frailty including Fried Criteria	To examine the effect of study drug (compared to placebo) on markers of physical frailty (frailty phenotype).	4 months
Secondary	Kidney function including estimated glomerular filtration rate	To examine the effect of study drug (compared to placebo) on kidney function.	4 months
Secondary	Kidney function including urine protein excretion rate	To examine the effect of study drug (compared to placebo) on kidney function protein excretion	4 months
Secondary	Number of participants with treatment-related adverse events including hospitalization	To assess the safety and tolerability of study drug taken over two days (compared to placebo)	12 months