AFFIRM-LITE: Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT03675724

Collaborator

(none)

Enrollment

Location

Arms

55.5

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Frail Elderly Syndrome	Dietary Supplement: Fisetin Drug: Placebo oral capsule	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 15, 2018

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Fisetin 20mg/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

Arm

Intervention/Treatment

Experimental: Treatment

Fisetin 20mg/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

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.