Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women (AFFIRM)

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

This is a pilot study to evaluate whether targeting inflammation will help reduce markers of insulin resistance inflammation, bone resorption and physical dysfunction in elderly women with gait disturbance. Positive results of this study would lead to the development of a larger clinical trial examining the effects of this intervention on age-related dysfunction.

Study Overview

• Status: Enrolling by invitation
• Conditions: Frail Elderly Syndrome
• Intervention / Treatment: Drug: Placebo oral capsule; Dietary supplement: Fisetin

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 postmenopausal women. The researchers plan to evaluate markers of frailty and markers of inflammation, insulin resistance, and bone resorption while maintaining bone formation in older postmenopausal women.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tamara K Evans; Phone Number: 507-284-1004; Email: evans.tamara@mayo.edu

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Healthy postmenopausal women
• Age ≥ 70 years

Exclusion Criteria

• Abnormality in any of the screening laboratory studies (see below)
• Presence of significant liver or renal disease
• Malignancy (including myeloma)
• Malabsorption
• Hypoparathyroidism
• Hyperparathyroidism
• Acromegaly
• Cushing's syndrome
• Hypopituitarism
• Gastric bypass/reduction
• Malabsorption issues
• Crohn's
• Myopathies (increased or low calcium, vitamin D deficiency, elevated creatine kinase or ESR)
• If diabetic AND on sulfonylureas (like glipizide, glimepiride, glyburide), SGLT2 inhibitors (like dapagliflozin and empagliflozin), or insulin

• Undergoing treatment with any medications that affect bone turnover, including the following:

  • adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr), anticonvulsant therapy (within the previous year),
  • pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal),
  • calcium supplementation of > 1200 mg/d (within the preceding 3 months),
  • bisphosphonates (within the past 3 yrs),
  • denosumab,
  • estrogen (E) therapy or treatment with a selective E receptor modulator, or teriparatide (within the past yr).
• Subjects with a fracture within the past year
• 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
• QTc >450 msec
• Inability to provide informed consent
• Total bilirubin >2X upper limit
• Inability to tolerate oral medication
• eGFR < 15 ml/ min/ 1.73 m2
• Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc.)
• 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 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, thyroid hormones, eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, warfarin, heparin, full dose ASA, clopidogrel, 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Fisetin 20/mg/kg/day, orally for 2 consecutive days, for 2 consecutive months.	Dietary supplement: Fisetin; Flavonoid Family
Placebo Comparator: Placebo; Placebo capsules orally for 2 consecutive days, for 2 consecutive months.	Drug: Placebo oral capsule; Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved 6 minute walk	Improved gait speed	One Month

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Sundeep Khosla, MD, Mayo Clinic; Principal Investigator: James L Kirkland, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2018
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: February 5, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Frailty
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Frailty
• Other Study ID Numbers: 17-000472

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