The Use of Senolytic Agent to Improve the Benefit of Platelet-Rich Plasma and Losartan for Treatment of Femoroacetabular Impingement and Labral Tear: A Pilot Study

ENROLLMENT COMPLETE

Principal Investigators: Marc J. Philippon, M.D. and Johnny Huard, Ph.D.

This study is being conducted at The Steadman Clinic and Steadman Philippon Research Institute and is supported by The United States Department of Defense. The purpose of the study is to study the effects of a pre- and post-operative senolytic medication (Fisetin) for femoroacetabular impingement and labral repair.

For additional information, please visit www.clinicaltrials.gov and search for: NCT05025956

Primary Objectives

• To determine whether pre- and post-operative Fisetin will improve the benefits of PRP when used in conjunction with hip arthroscopy for the treatment of femoroacetabular impingement and labral tears.
• To determine whether pre- and post-operative Fisetin for hip arthroscopy decreases serum biomarkers of SASP and inflammation.
• To determine whether Fisetin prior to undergoing hip arthroscopy is safe.

Procedures Include

• Review of your medical record
• Pregnancy test if you are a woman of child-bearing age
• Blood draw
• Questionnaires
• Physical exam
• Administration of Fisetin, an experimental dietary investigational drug, or Fisetin Placebo
• Recording of study drug doses in a diary in between visits

Eligibility Criteria

Inclusion
You may be able to participate if all the following criteria are true:

1. Capacity to personally give informed consent (consent via legally authorized representative will not be accepted) and who are willing to comply with all study-related procedures and assessments;
2. Between 18 and 80 years of age;
3. Have been diagnosed with femoroacetabular impingement (FAI) and/or a hip labral tear;
4. Are scheduled to undergo hip arthroscopy to treat FAI and /or a hip labral tear;

Exclusion
You cannot participate if any of the following criteria are true:

Previous or Planned Hip Surgeries, Procedures and/or Treatments:

1. Planned surgery on either the contralateral or target hip at any time during the Study period including dosing and follow-up;
2. Require microfracture on the target hip as part of the planned arthroscopy;
3. Within 6 months of signing informed consent, has undergone regenerative hip joint procedures on the target hip including, but not limited to, platelet-rich plasma injections, mesenchymal stem cell transplantation
4. Have had previous surgery (including microfracture) or diagnostic arthroscopy on the target hip;
5. Joint space less than ≤2mm;
6. Tönnis Grade 2-3;.
7. Have a history of pigmented villonodular synovitis (joint disease characterized by inflammation and overgrowth of the synovial lining of the hip joint);
8. Have a history of synovial chondromatosis (noncancerous tumor that develops in the synovial lining of the hip joint);
9. Have a history of hip dysplasia requiring PAO;
10. History of Avascular Necrosis (AVN), Perthes disease, or slipped capital femoral epiphysis (SCFE);
11. Any active known or suspected systemic autoimmune disease (except for vitiligo, residual auto-immune hypothyroidism requiring hormone replacement only, psoriasis not requiring systemic treatment for two years, conditions not expected to recur in the absence of an external trigger) or any history of a systemic inflammatory arthritis such as psoriatic, rheumatoid, ankylosing spondylitis or reactive arthritis;
12. Current diagnosis of fibromyalgia based on ACR criteria;
13. Are unable to or are unwilling to receive a PRP injection as part of your surgery;
14. Inadequate amount of PRP collected to serve the needs of the patient, and/or ProofPoint Biologics,.
15. Within 2 years of signing informed consent,  history of active blood clotting disorders requiring preventative treatment, or active malignancy of any type or history of a malignancy (with the exception of subjects with a history of treated basal or squamous cell carcinoma);
16. Baseline HbA1C greater than 6.5, uncontrolled diabetes mellitus, and/or medication management has not been stable in the previous 2 months;
17. Current or prior history of other joint diseases that may (in the opinion of the Principal Clinical Investigator or his/her designee) confound study data or increase Subject risk. These may include including but not limited to joint dysplasia, crystal-induced arthropathy (such as gout, or calcium pyrophosphate deposition disease evidenced by clinical and/or radiographic means), aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Stickler syndrome, joint infection, hemochromatosis, or neuropathic arthropathy of any cause;
18. Any medical condition, including findings in laboratory or medical history or in the baseline assessments, that (in the opinion of the Principal Clinical Investigator or his/her designee), constitutes a risk or contraindication for participation in the Study or that could interfere with the Study conduct, endpoint evaluation or prevent the subject from fully participating in all aspects of the Study;
19. Females who are nursing a child, are pregnant, or who are planning to become pregnant during study drug dosing, or who are not willing to abstain from sex without the use of contraceptive protection during study drug dosing;
20. Males who do not wish to abstain from sex with women of childbearing potential without use of contraceptive protection during study drug dosing;
21. Currently taking warfarin or any drug that could cause a coagulopathy event;
22. Within 1 week of signing informed consent. taking medications that affect insulin activity, including Metformin or Acarbose
23. Have an allergy to any active or inactive ingredient of Losartan or Fisetin, and/or currently taking medication with known adverse  Losartan or Fisetin interaction;
24. Within 3 months of signing informed consent have taken senolytic agents including: Fisetin, Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax;
25. Currently taking the following drugs if they cannot be held for at least 2 days (per enrolling Principal Investigator or Sub Investigator, or healthcare professional appropriately delegated by the Principal Investigator) before and during administration of Fisetin: cyclosporine, tacrolimus, repaglinide, and bosentan;
26. Currently taking drugs that induce cellular senescence, including alkylating agents, anthracyclines, platins, other chemotherapy;
27. Within 1 month of signing informed consent, taking a glucocorticoid
28. Has current history of drug and/or alcohol abuse;
29. Within the 3 months of signing informed consent has received anticonvulsant therapy, pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal).
30. Within the 12 months prior to signing informed consent received any medications that affect bone turnover, including: adrenocorticosteroids (> 3 months at any time or > 10 days, estrogen (E) therapy or treatment with a selective E receptor modulator, or teriparatide;
31. Inability to tolerate oral medication.

If you would like more information about the study, please contact us at clinicaltrials@sprivail.org or 970-401-8770.