Senolytic Agent Improve the Benefit of Platelet-Rich Plasma and Losartan

NCT05025956 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 2020-058
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose is to explore the possible benefit of administration of Fisetin, (a senolytic agent) to improve the benefit of Platelet-Rich Plasma and losartan for treatment of femoroacetabular impingement and labral tear. We believe that giving Fisetin, a senolytic agent, will improve the benefit of PRP by eliminating senescent cells and senescence-associated secretory phenotype (SASP), known to exist in PRP. The main objectives of this study are to determine if pre- and post-operative administration of a senolytic agent will improve the beneficial effects of PRP when used in conjunction with surgical treatment of FAI and/or labral tear, to determine whether pre- and postoperative administration of Fisetin is associated with adverse events, and to determine if pre- and post-operative administration of Fisetin leads to a decrease in systemic senescence, serum SASP, and fibrotic markers. Patients suffering from femoroacetabular impingement and labral tear, who are planning to undergo hip arthroscopy combined with standard of care intra-operative PRP injection and post-operative losartan administration will be recruited from the clinical practice of the Principal Clinical Investigator or his designee at The Steadman Clinic (TSC).

Conditions

Femoroacetabular Impingement

Keywords

FAI Labral tear Fisetin Losartan

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Occurrence of adverse events

  From date of study drug dosing until the end of the study, an average of 12 months

Secondary Outcomes (9)

• Patient Reported Outcomes Questionnaire-Modified Harris Hip Score (mHHS)

  Baseline, 8-12 weeks post-op, 6 months post-op, and 12 months post-op

• Patient Reported Outcomes Questionnaire- Hip Outcome Score: activities of daily living and sports subscales (HOS-ADL, HOS-SSS)

  Baseline, 8-12 weeks post-op, 6 months post-op, and 12 months post-op

• Patient Reported Outcomes Questionnaire-Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

  Baseline, 8-12 weeks post-op, 6 months post-op, and 12 months post-op

• Patient Reported Outcomes Questionnaire-Optum Short Form physical and mental component scores (SF-12 PCS and SF-12 MCS)

  Baseline, 8-12 weeks post-op, 6 months post-op, and 12 months post-op

• Patient Reported Outcomes Questionnaire-Tegner Activity Scale

  Baseline, 8-12 weeks post-op, 6 months post-op, and 12 months post-op

Study Arms (2)

Fisetin group (investigational group)

EXPERIMENTAL

20mg/kg of Fisetin per day for days 1 and 2 prior to surgery and days 33, 34, 63, 64, 93, and 94 post surgery. (The pills are 100mg each. For example, if a participant weighs 160 pounds (about 73 kg), the participant will need to take 15 pills per day)

Drug: Fisetin

Placebo group (control group)

PLACEBO COMPARATOR

20mg/kg of Placebo per day for days 1 and 2 prior to surgery and days 33, 34, 63, 64, 93, and 94 post surgery. (The pills are 100mg each. For example, if a participant weighs 160 pounds (about 73 kg), the participant will need to take 15 pills per day)

Drug: Placebo

Interventions

Fisetin DRUG

Oral Fisetin 20 mg/kg taken for 8 days total.

Also known as: Novusetin, 7,3',4'-flavon-3-ol, 3,3',4',7-tetrahydroxyflavone

Fisetin group (investigational group)

Placebo DRUG

Fisetin appearance-matched microcrystalline cellulose placebo. 20 mg/kg taken for 8 days total.

Also known as: Placebo Oral Capsule

Placebo group (control group)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Between 18 and 80 years of age
• Have been diagnosed with femoroacetabular impingement (FAI) and/or a hip labral tear
• You are scheduled to undergo hip arthroscopy to treat FAI and /or a hip labral tear

You may not qualify if:

• Previous or Planned Hip Surgeries, Procedures and/or Treatments:
• Planned surgery on either the contralateral or target hip at any time during the Study period including dosing and follow-up
• Require microfracture on the target hip as part of the planned arthroscopy
• 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
• Have had previous surgery (including microfracture) or diagnostic arthroscopy on the target hip
• Joint space less than ≤2mm
• Tönnis Grade 2-3
• Have a history of pigmented villonodular synovitis (joint disease characterized by inflammation and overgrowth of the synovial lining of the hip joint)
• Have a history of synovial chondromatosis (noncancerous tumor that develops in the synovial lining of the hip joint);
• Have a history of hip dysplasia requiring PAO
• History of Avascular Necrosis (AVN), Perthes disease, or slipped capital femoral epiphysis (SCFE)
• 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
• Current diagnosis of fibromyalgia based on ACR criteria
• Are unable to or are unwilling to receive a PRP injection as part of your surgery
• Inadequate amount of PRP collected to serve the needs of the patient, and/or ProofPoint Biologics

Sponsors & Collaborators

• Steadman Philippon Research Institute: lead
• United States Department of Defense: collaborator

Study Sites (1)

The Steadman Clinic

Vail, Colorado, 81657, United States

Location

MeSH Terms

Conditions

Femoracetabular Impingement

Interventions

fisetin

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Johnny L Huard, PhD

  Steadman Philippon Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Investigator or properly trained and delegated study team member (research PA) will write the prescription for the study medication. The subject's randomization block and within-block random number will be communicated directly to the Vail Health pharmacy. The Vail Health pharmacy will maintain an unblinded, de-identified randomization spreadsheet that documents group allocation for each subject. The Vail Health Pharmacy oversees and manages drug disbursement for research.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: pilot, prospective, randomized, double-blind, placebo control clinical trial

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 30, 2021
• Study Start: October 24, 2021
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)