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Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults (AFFIRM-LITE)

Primary Purpose

Frail Elderly Syndrome

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fisetin
Placebo oral capsule
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Frail Elderly Syndrome focused on measuring Frailty, Inflammation, Elderly, Aging

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

• Age ≥ 70 years

Exclusion Criteria

  • Unable or unwilling to give informed consent
  • Pregnant
  • Body weight >150 kg or body mass index (BMI) > 50
  • QTc>450 msec
  • Total bilirubin >2X upper limit of normal
  • Inability to tolerate oral medication
  • Abnormality in any of the screening laboratory studies (see below)
  • Human immunodeficiency virus infection
  • Known active hepatitis B or C infection
  • Invasive fungal or viral infection
  • Known hypersensitivity or allergy to fisetin
  • Uncontrolled pleural/pericardial effusions or ascites
  • New/active invasive cancer except non-melanoma skin cancers
  • Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic.
  • Strong inhibitors of CYP3A4. See Appendices 1-3.
  • Tyrosine kinase inhibitor therapy
  • Known hypersensitivity or allergy to fisetin
  • Subjects on quinolone antibiotic therapy for treatment or for prevention of infections within 10 days.
  • Subjects taking H2-antagonists and unwilling to discontinue therapy for 1 week before and 2 weeks following enrollment.
  • 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
  • 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 2 days 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, , eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, 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.
  • Presence of any condition that the Investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial.

Behavioral Modification - Participants will be educated about the risk of excessive caffeine usage. Participants will be encouraged to reduce use by 50% prior to and during the 2-day drug dosing period. Due to drug-drug interaction, subjects may not clear the caffeine from their system properly/as usual.

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 20mg/kg/day, orally for 2 consecutive days

Placebo capsules orally for 2 consecutive days

Outcomes

Primary Outcome Measures

Decrease in blood inflammation markers
Percent decrease in blood inflammation markers

Secondary Outcome Measures

Full Information

First Posted
September 17, 2018
Last Updated
January 25, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT03675724
Brief Title
Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults
Acronym
AFFIRM-LITE
Official Title
AFFIRM-LITE: A Phase 2 Randomized, Placebo-Controlled Study of Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 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 test the efficacy of the anti-inflammatory drug (Fisetin) in reducing inflammatory factors in blood in elderly adults and to test the efficacy of the drug (Fisetin) in reducing frailty and markers of inflammation, insulin resistance, and bone resorption in elderly adults.
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 adults. The researchers plan to evaluate markers of frailty and markers of inflammation, insulin resistance, and bone resorption while maintaining bone formation in older adults.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Frail Elderly Syndrome
Keywords
Frailty, Inflammation, Elderly, Aging

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 20mg/kg/day, orally for 2 consecutive days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsules orally for 2 consecutive days
Intervention Type
Dietary Supplement
Intervention Name(s)
Fisetin
Intervention Description
Flavonoid Family
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Decrease in blood inflammation markers
Description
Percent decrease in blood inflammation markers
Time Frame
Seven Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria • Age ≥ 70 years Exclusion Criteria Unable or unwilling to give informed consent Pregnant Body weight >150 kg or body mass index (BMI) > 50 QTc>450 msec Total bilirubin >2X upper limit of normal Inability to tolerate oral medication Abnormality in any of the screening laboratory studies (see below) Human immunodeficiency virus infection Known active hepatitis B or C infection Invasive fungal or viral infection Known hypersensitivity or allergy to fisetin Uncontrolled pleural/pericardial effusions or ascites New/active invasive cancer except non-melanoma skin cancers Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic. Strong inhibitors of CYP3A4. See Appendices 1-3. Tyrosine kinase inhibitor therapy Known hypersensitivity or allergy to fisetin Subjects on quinolone antibiotic therapy for treatment or for prevention of infections within 10 days. Subjects taking H2-antagonists and unwilling to discontinue therapy for 1 week before and 2 weeks following enrollment. 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 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 2 days 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, , eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, 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. Presence of any condition that the Investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial. Behavioral Modification - Participants will be educated about the risk of excessive caffeine usage. Participants will be encouraged to reduce use by 50% prior to and during the 2-day drug dosing period. Due to drug-drug interaction, subjects may not clear the caffeine from their system properly/as usual.
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

Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

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

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