Overview

Senolytic Drugs Attenuate Osteoarthritis-Related Articular Cartilage Degeneration: A Clinical Trial

Status:
Active, not recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
All
Summary
Phase I/II randomized, double-blind, placebo-controlled clinical trial to test the safety and efficacy of Fisetin for treating mild to moderate osteoarthritis
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Steadman Philippon Research Institute
Collaborators:
Office of Naval Research (ONR)
United States Department of Defense
Criteria
Inclusion Criteria:

Subjects will be included if all the following criteria are met:

1. Are male or female, ages 40-80;

2. Are willing to comply with all study related procedures and assessments;

3. Are ambulatory as defined by ability to complete functional performance testing;

4. Radiographic evidence of Kellgren-Lawrence grade II-IV osteoarthritis in one or both
knees;

5. Scores 4-10 on the Numerical Rating Scale (NRS) for pain;

6. Stable dose of screening/baseline medications for at least 2 months prior to the
anticipated date of study drug dosing.

Exclusion Criteria:

Subjects will be excluded if any of the following criteria are met:

1. Females who are nursing, pregnant or planning to become pregnant during the duration
of study drug dosing;

2. Males who do not wish to abstain from sex or use contraceptive protection during study
drug dosing and for 2 weeks after the last dose;

3. Subjects who do not have the capacity to consent themselves;

4. Subjects who are unable to tolerate oral medication;

5. Subjects having previously undergone any of the following treatments in the stated
time window.

- Surgery on the Study Knee in the past 6 months;

- Partial or complete joint replacement in the study knee. Partial or complete
joint replacement in the contralateral knee is acceptable as long as the surgery
was performed at least 6 months prior to enrollment and the operative knee is
asymptomatic;

- Patients who have undergone arthroscopic surgery (including microfracture and
meniscectomy) on the Study Knee in the last 2 years prior to the Screening visit
or are anticipated to have arthroscopic surgery on either knee at any time during
the study period;

- Steroid injection, including extended-release corticosteroid (e.g., Zilretta®)
within the last 5 months;

- Biologic (platelet-rich plasma, bone marrow, adipose tissue/cells) or hyaluronic
acid injection into the Study Knee in the past 6 months;

6. Subjects with any of the following drug/medication statuses:

- Currently taking Losartan;

- Currently taking Warfarin or related anticoagulants;

- Opioid analgesics taken in the past 8 weeks and are not willing to discontinue
these medications through the duration of the study;

- Senolytic agents taken within the past 6 months and are not willing to
discontinue these medications through the duration of the study, including:
Fisetin, Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax;

- Drugs that induce significant cellular stress and are not willing to discontinue
these medications through the duration of the study, including alkylating agents,
anthracyclines, platins, other chemotherapy drugs;

- Subjects taking the following other drugs if they cannot be held (per the
Principal Investigator) for at least 2 days before and during administration of
Fisetin: cyclosporine, tacrolimus, repaglinide, and bosentan.

7. Subjects with any of the following disease statuses:

- Significant liver disease (i.e. greater than or equal to 2x the upper limit of
normal bilirubin levels) or as in the opinion of the Principal Investigator;

- Significant renal disease (eGFR of <60 ml/min/1.73m2) or as in the opinion of the
Principal Investigator;

- History of other formally diagnosed joint diseases including osteonecrosis,
acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Cushing's
syndrome, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, or
neuropathic arthropathy of any cause;

- Any active systemic autoimmune disease with musculoskeletal involvement or any
history of system inflammatory arthritis;

- Patients with type 1 or 2 diabetes (HbA1c>6.5%) and/or taking medications that
affect insulin levels, including: Metformin (within the last week),
Glucocorticoids (within the last month), Acarbose (within the last week);

8. Subjects unable to safely practically undergo an MRI (BMI > 40 kg/m2) or size
exceeding limits of MRI equipment, implanted metal in study knee near joint surface,
incompatible implant/device, severe claustrophobia;

9. Subjects that have any medical condition, including laboratory findings and findings
in the medical history or in the pre-study assessments, that in the opinion of the
Investigator constitutes a risk or contraindication for participation in the study or
that could interfere with the study objectives, conduct or evaluation or prevent the
patient from fully participating in all aspects of the study.