Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women (AFFIRM)
Primary Purpose
Frail Elderly Syndrome
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fisetin
Placebo oral capsule
Sponsored by
About this trial
This is an interventional treatment trial for Frail Elderly Syndrome focused on measuring Inflammation, Frailty
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.
Sites / Locations
- Mayo Clinic in RochesterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment
Placebo
Arm Description
Fisetin 20/mg/kg/day, orally for 2 consecutive days, for 2 consecutive months.
Placebo capsules orally for 2 consecutive days, for 2 consecutive months.
Outcomes
Primary Outcome Measures
Improved 6 minute walk
Improved gait speed
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03430037
Brief Title
Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women
Acronym
AFFIRM
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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 6, 2018 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Frail Elderly Syndrome
Keywords
Inflammation, Frailty
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Fisetin 20/mg/kg/day, orally for 2 consecutive days, for 2 consecutive months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsules orally for 2 consecutive days, for 2 consecutive months.
Intervention Type
Dietary Supplement
Intervention Name(s)
Fisetin
Intervention Description
Flavonoid Family
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Other Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Improved 6 minute walk
Description
Improved gait speed
Time Frame
One Month
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tamara K Evans
Phone
507-284-1004
Email
evans.tamara@mayo.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James L Kirkland, MD, PhD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sundeep Khosla, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tamara K Evans
Phone
507-284-1004
Email
evans.tamara@mayo.edu
First Name & Middle Initial & Last Name & Degree
James Kirkland, MD, PhD
First Name & Middle Initial & Last Name & Degree
Sundeep Khosla, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women
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