Clinical trial NCT03430037: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Frail Elderly Syndrome
Keywords: Inflammation
Frailty
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2018-02-12
Enrollment: 40
Sex: FEMALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Improved 6 minute walk
timeFrame: One Month
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Robert J Pignolo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Sundeep Khosla, MD
role: PRINCIPAL_INVESTIGATOR
References: