Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults

Frail Elderly Syndrome Clinical Trial

— AFFIRM-LITE  

Official title:

AFFIRM-LITE: A Phase 2 Randomized, Placebo-Controlled Study of Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03675724
• Other study ID #: 18-007332
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: November 15, 2018
• Est. completion date: October 2024

Study information

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

Clinical Trial Summary

This is a pilot study to test the efficacy of the anti-inflammatory drug (Fisetin) in reducing inflammatory factors in blood in elderly adults and to test the efficacy of the drug (Fisetin) in reducing frailty and markers of inflammation, insulin resistance, and bone resorption in elderly adults.

Description:

To the researchers' knowledge, there are no published studies utilizing Fisetin in alteration of frailty markers. Several studies involve use of Fisetin for its anti-oxidative and anti-apoptotic effects in animal models. Fisetin may reduce oxidative stress, alleviate hyperglycemia, and improve kidney function. No one has evaluated the biologic markers of inflammation and frailty in older adults. The researchers plan to evaluate markers of frailty and markers of inflammation, insulin resistance, and bone resorption while maintaining bone formation in older adults.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 40
• Est. completion date: October 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria

• Age = 70 years

Exclusion Criteria

• Unable or unwilling to give informed consent

• Pregnant

• Body weight >150 kg or body mass index (BMI) > 50

• QTc>450 msec

• Total bilirubin >2X upper limit of normal

• Inability to tolerate oral medication

• Abnormality in any of the screening laboratory studies (see below)

• Human immunodeficiency virus infection

• Known active hepatitis B or C infection

• Invasive fungal or viral infection

• Known hypersensitivity or allergy to fisetin

• Uncontrolled pleural/pericardial effusions or ascites

• New/active invasive cancer except non-melanoma skin cancers

• Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic.

• Strong inhibitors of CYP3A4. See Appendices 1-3.

• Tyrosine kinase inhibitor therapy

• Known hypersensitivity or allergy to fisetin

• Subjects on quinolone antibiotic therapy for treatment or for prevention of infections within 10 days.

• Subjects taking H2-antagonists and unwilling to discontinue therapy for 1 week before and 2 weeks following enrollment.

• Subjects taking potentially senolytic agents within the last year: Fisetin, Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax

• Subjects currently taking drugs that induce cellular senescence: alkylating agents, anthracyclines, platins, other chemotherapy

• Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin,erythromycin), Antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir), Rifampin

• Subjects taking proton pump inhibitors who are unable or unwilling to reduce or hold therapy 2 days prior to and during the 2-day Fisetin dosing

• Subjects taking the following other drugs if they cannot be held for at least 2 days before and during administration of Fisetin: digoxin, lithium, all statins, repaglidine, bosentan, gemfibrozil, olmesartan, enalapril, valsartan, methotrexate, corticosteroids, , eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, celecoxib, desipramine, thioridazine, venlafaxine, tizanidine, atomoxetine, voriconazole, citalopram, diazepam, escitalopram, propranolol, clozapine, cyclobenzaprine, mexiletine, olanzapine, ondansetron, riluzole

• In order to ensure vitamin D sufficiency, we will also exclude subjects with serum 25-hydroxyvitamin D levels of < 20 ng/ml.

• 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.

Behavioral Modification - Participants will be educated about the risk of excessive caffeine usage. Participants will be encouraged to reduce use by 50% prior to and during the 2-day drug dosing period. Due to drug-drug interaction, subjects may not clear the caffeine from their system properly/as usual.

Related Conditions & MeSH terms

• Frail Elderly Syndrome
• Frailty
• Inflammation

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	Decrease in blood inflammation markers	Percent decrease in blood inflammation markers	Seven Days

External Links

•   Mayo Clinic Clinical Trials