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

Frail Elderly Syndrome Clinical Trial

— AFFIRM  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03430037
• Other study ID #: 17-000472
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: February 6, 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 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.

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.

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: Female
• Age group: 70 Years and older

Eligibility

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.

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	Improved 6 minute walk	Improved gait speed	One Month

External Links

•   Mayo Clinic Clinical Trials