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

• ClinicalTrials.gov Identifier: NCT03430037
• Recruitment Status: Recruiting
• First Posted: February 12, 2018
• Last Update Posted: January 11, 2022
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): James L. Kirkland, MD, PhD, Mayo Clinic

Tracking Information

• First Submitted Date: February 5, 2018
• First Posted Date: February 12, 2018
• Last Update Posted Date: January 11, 2022
• Actual Study Start Date: February 6, 2018
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2018)

Improved 6 minute walk [ Time Frame: One Month ]

Improved gait speed

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women
• Official Title: AFFIRM: A Phase 2 Randomized, Placebo-Controlled Study of Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women
• Brief Summary: 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.
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Frail Elderly Syndrome

Intervention

• Dietary Supplement: Fisetin
  Flavonoid Family
• Drug: Placebo oral capsule
  Placebo
  Other Name: Placebo

Study Arms

• Experimental: Treatment
  Fisetin 20/mg/kg/day, orally for 2 consecutive days, for 2 consecutive months.
  Intervention: Dietary Supplement: Fisetin
• Placebo Comparator: Placebo
  Placebo capsules orally for 2 consecutive days, for 2 consecutive months.
  Intervention: Drug: Placebo oral capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 9, 2018): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 70 Years and older (Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tamara K Evans; 507-284-1004; evans.tamara@mayo.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03430037
• Other Study ID Numbers: 17-000472
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: James L. Kirkland, MD, PhD, Mayo Clinic
• Original Responsible Party: James L. Kirkland, Mayo Clinic, Principal Investigator
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Mayo Clinic
• Verification Date: January 2022