Osteoarthritis, KneePhase 1/2NCT04815902
Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis
A Phase 1/2 study testing Fisetin and Losartan in people with Osteoarthritis, Knee, run by Steadman Philippon Research Institute at 1 site in United States.
Trial summary
This is a prospective, randomized, double-blind, active control clinical trial to evaluate the safety and efficacy of a senolytic agent (Fisetin) and an anti-fibrotic agent (Losartan), used independently and in combination, to improve beneficial effect demonstrated by the active control which is to be injection of… Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- Fisetin and Losartan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2021to 1 Jun 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 40 and 85 years of age;
- Ambulatory persons with osteoarthritis (OA) of at least one knee (Kellgren-Lawrence grade II-IV);
- Baseline pain of 3-10 points on the target knee and a pain differential of at least -2 points on the contralateral knee as exhibited by the worst pain score (on the 11-point Numeric Rating Scale) for the previous week.
Who cannot join
- Previous or Planned Knee Surgeries, Procedures and/or Treatments:
- Planned surgery on either the contralateral or target knee at any time during the Study period including dosing and follow-up;
- Within 6 months of signing informed consent has received diagnostic arthroscopy of the target knee or arthroscopic surgery (including microfracture and meniscectomy) on the target knee;
- Within 12 weeks of signing informed consent has received intra-articular treatment of the target knee with steroids or hyaluronic acid derivatives;
- History of previous total or partial arthroplasty in the target knee. Partial or total arthroplasty 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;
- Current and/or Previous Medical Conditions, Surgeries and/or Procedures:
Show all 36Show fewer
- Within 2 years of signing informed consent history of active blood disorders (i.e., DVTs, chronic blood clotting, hemophilia, leukemia, myeloma, etc.); 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);
- Current diagnosis of fibromyalgia based on ACR criteria;
- History of diabetes mellitus according to the American Diabetes Association criteria, or subjects previously diagnosed by a qualified physician as having diabetes (American Diabetes Association Standards of Medical Care in Diabetes 2016);
- 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;
- Within 6 months of signing informed consent has undergone regenerative knee joint procedures including, but not limited to, platelet-rich plasma injections, mesenchymal stem cell transplantation, autologous chondrocyte transplantation, or mosaicplasty;
- Current or prior history of other joint diseases 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;
- Any medical condition, including findings in laboratory or medical history or in the baseline assessments, that (in the opinion of the Principal Investigator or his 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;
- Females who nursing a child, are pregnant or planning to become pregnant during study drug dosing;
- Males who do not wish to abstain from sex with women of childbearing potential without use of contraceptive protection by either party during study drug dosing;
- Unable to safely undergo an MRI based on MRI safety screening (for example, due to incompatible device/implant, severe claustrophobia, BMI greater than 40 kg/m2, or size exceeding the limits of the of the MRI equipment (coil and gantry);
- Current and/or Previous Medications and Supplements:
- Taking medications that affect insulin activity, including Metformin or Acarbose within 1 week of signing informed consent;
- Currently taking Losartan or Fisetin, allergy to any active or inactive ingredient of Losartan or Fisetin, and/or currently taking medication with known Losartan or Fisetin interaction;
- Within 3 months of signing informed consent have taken senolytic agents including: Fisetin, Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax;
- Subjects with any of the following drug/medication statuses:
- Currently taking Losartan;
- Currently taking Warfarin or related anticoagulants;
- Currently taking Lithium;
- 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 3 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.
- Taking a glucocorticoid within 1 month of signing informed consent;
- Within 8 weeks of signing informed consent has used opioid analgesics, and are not willing to discontinue these medications through the duration of the study;
- 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), calcium supplementation of > 1200 mg/d;
- 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;
- Inability to tolerate oral medication;
- Inadequate amount of BMA collected to serve the needs of the patient, ProofPoint Biologics and/or of the SPRI laboratory.
- 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 Fisetin dosing days. Due to drug-drug interaction, subjects may not clear the caffeine from their system properly/as usual.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis
This is a prospective, randomized, double-blind, active control clinical trial to evaluate the safety and efficacy of a senolytic agent (Fisetin) and an anti-fibrotic agent (Losartan), used independently and in combination, to improve beneficial effect demonstrated by the active control which is to be injection of autologous bone marrow aspirate concentrate (BMAC) into an osteoarthritic knee.
Read the detailed description
This is a prospective, randomized, double-blind, active control clinical trial to evaluate the safety and efficacy of a senolytic agent (Fisetin) and an anti-fibrotic agent (Losartan), used independently and in combination, to improve beneficial effect demonstrated by the active control which is to be injection of autologous bone marrow aspirate concentrate (BMAC) into an osteoarthritic knee. 100 subjects with symptomatic unilateral or bilateral knee osteoarthritis (Kellgren-Lawrence grade II-IV) will be randomized into one of four arms (1:1:1:1). All subjects will receive an injection of BMAC. Group 1-n=25: Control (BMA concentrate + Fisetin Placebo + Losartan Placebo) Group 2-n=25: BMA concentrate + Fisetin Placebo + Active Losartan Group 3-n=25: BMA concentrate + Active Fisetin + Losartan Placebo Group 4-n=25: BMA concentrate + Active Fisetin + Active Losartan
- Conditions
- Osteoarthritis, Knee
- Being tested
- Fisetin, Losartan, Placebo - Losartan, Placebo Fisetin
- Keywords
- Fisetin, Losartan, Osteoarthritis, Knee, Bone Marrow Concentrate, Bone Marrow Aspirate
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FisetinDrug
Also called Novusetin, 7,3',4'-flavon-3-ol, 3,3',4',7-tetrahydroxyflavone
Oral Fisetin 20 mg/kg taken for 10 days total.
LosartanDrug
Also called Losartan potassium
12.5 mg oral Losartan taken for 30 days total.
Placebo - LosartanDrug
Also called Placebo Oral Capsule
Losartan appearance-matched microcrystalline cellulose placebo. 12.5 taken for 30 days total.
Placebo FisetinDrug
Also called Placebo Oral Capsule
Fisetin appearance-matched microcrystalline cellulose placebo. 20 mg/kg taken for 10 days total.
| Study group | Role | What they receive |
|---|---|---|
| Active Fisetin and Active Losartan | Experimental | Losartan 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). Receives: Drug: Fisetin; Drug: Losartan |
| Active Fisetin and Losartan Placebo | Active comparator | Losartan Placebo 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). Receives: Drug: Fisetin; Drug: Placebo - Losartan |
| Fisetin Placebo and Active Losartan | Active comparator | Losartan 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin Placebo 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). Receives: Drug: Losartan; Drug: Placebo Fisetin |
| Control | Placebo comparator | Losartan placebo 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin Placebo 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). Receives: Drug: Placebo - Losartan; Drug: Placebo Fisetin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Occurrence of adverse events
Measured: Adverse events will be collected from the date of BMAC injection to 12 months after injection
Secondary outcomes (19)
Morphological and Quantitative Magnetic Resonance Imaging (MRI)
Cartilage quality assessed by blinded radiologist using morphological MRI. Quantitative MRI using T2 mapping images with texture analysis used to assess water content and collagen organization within the cartilage and surrounding tissue
Measured: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection)
Evaluation of patient reported outcome (PRO) for quality of life
12-question Short-Form General Health Survey (SF-12) - Including Physical Component Summary (PCS) and Mental Component Summary (MCS).
Measured: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Evaluation of patient reported outcome (PRO) for knee functions (WOMAC)
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (24 questions; rated none, mild, moderate, or severe. Higher WOMAC score represents higher disability)
Measured: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Evaluation of patient reported outcome (PRO) for knee functions (Tegner)
Tegner Physical Activity Scale (1 question; scale of 0 to10; 0 representing a low activity level and 10 representing a high activity level)
Measured: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Evaluation of patient reported outcome (PRO) for knee functions (IKDC)
International Knee Documentation Committee (IKDC) Form. (scores range from 0 points or lowest level of function, to 100 points or highest level of function)
Measured: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Patient-Reported Outcome Questionnaires
Numerical Rating Scale (NRS) for knee pain (6 questions with a scale of 0 to 10; 0 representing no pain and 10 representing extreme pain)
Measured: Screening, weekly post 1st study drug dose (pre-injection), weekly post injection (for 4 months)
Change in muscle strength of the study knee
Isokinetic Dynamometry
Measured: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (LEK)
Lower Extremity Kinematics
Measured: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (Stair Test)
Stair Test
Measured: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection]
Change in physical function of the Study Knee (fast 40-meter walk)
Fast 40-meter walk
Measured: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (TUG)
Timed up-and-go test
Measured: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (6-minute walk test)
6-minute walk test
Measured: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection]
Change in associate biomarkers as compared to placebo in peripheral blood plasma/serum
Immunoassays for Biomarker assessment from blood serum. Analytes will be measured via immunoassays. The following analytes will be measured and reported in pg/ml. IL-1b, IL-6, IL-15, IL-1a, IL-1Ra, IL-7, IL-8, MCP-1, TNF-a , RANTES, VEGF, IFN-g, GRO, IP10, Eotaxin, PDGF-AA, PDGFAB-BB, EGF, FLT3L, GDF15, GDF11, FGF21, IL-18, SOST, OC, FGF-23, PTH, Leptin, Insulin, TIMP1, TIMP2, TGF-b1, TGF-b2, MMP-1, MMP-2, MMP-9, MMP-10, HA, COMP, CS846, CRP.
Measured: screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection
Change in CTX-II as compared to placebo in urine
Immunoassays for CTX-II detection in urine reported as pg/ml
Measured: 32 days post baseline, 6 months post injection, 12 months post injection
Change in levels of senescent PBMCS (total and specific PBMC subsets such as T-Cells)
Flow Cytometry based detection and quantification of senescent PBMCs isolated from whole blood. Intensity of the fluorescent marker C12FDG will be measured. Cells positive for C12FDG will be quantified and designated as senescent.
Measured: screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection
Change in synovial fluid content
Synovial Fluid Analysis
Measured: 32 days post baseline, 6 months post injection, 12 months post injection
Characterization of Bone Marrow Derived Aspirate Concentrate cell content prior to injection
BMAC Analysis
Measured: 32 days post baseline
Characterization of Bone Marrow Derived plasma biomarkers prior to injection
BMAC Analysis
Measured: 32 days post baseline
Change in time to conversion to alternative treatment
Alternative procedure as indicated. The time to resort to alternative therapy from baseline will be recorded
Measured: Subjects may receive alternative treatment at any point during the 18-month study, continued participation will be determined on an individual basis (The time to resort to alternative therapy from baseline will be recorded)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2021
- Study start18 May 2021
- Primary completion1 Feb 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Steadman Philippon Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Johnny Huard, PhD, Principal investigator, Steadman Philippon Research InstituteMarc Philippon, MD, Principal investigator, Steadman Philippon Research InstituteScott L Tashman, PhD, Principal investigator, Steadman Philippon Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04815902
- Sponsor's protocol ID
- 2020-15
- Other IDs
- 1UG3AR077748-01
- Status last verified
- Apr 2024
- First submitted
- 17 Mar 2021
- Last updated
- 16 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Senolytic and Anti-Fibrotic Agents to Improve the Beneficial Effect of Bone Marrow Stem Cells for Osteoarthritis
- ClinicalTrials.gov ID
- NCT04815902
- Acronym / sponsor ID
- 2020-15
- Conditions
- Osteoarthritis, Knee
- Keywords
- Fisetin, Losartan, Osteoarthritis, Knee, Bone Marrow Concentrate, Bone Marrow Aspirate
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Steadman Philippon Research InstituteUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 18 May 2021 (actual)
- Primary completion
- 1 Feb 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 25 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, randomized, double-blind, active control clinical trial to evaluate the safety and efficacy of a senolytic agent (Fisetin) and an anti-fibrotic agent (Losartan), used independently and in combination, to improve beneficial effect demonstrated by the active control which is to be injection of autologous bone marrow aspirate concentrate (BMAC) into an osteoarthritic knee.
Detailed description
This is a prospective, randomized, double-blind, active control clinical trial to evaluate the safety and efficacy of a senolytic agent (Fisetin) and an anti-fibrotic agent (Losartan), used independently and in combination, to improve beneficial effect demonstrated by the active control which is to be injection of autologous bone marrow aspirate concentrate (BMAC) into an osteoarthritic knee. 100 subjects with symptomatic unilateral or bilateral knee osteoarthritis (Kellgren-Lawrence grade II-IV) will be randomized into one of four arms (1:1:1:1). All subjects will receive an injection of BMAC. Group 1-n=25: Control (BMA concentrate + Fisetin Placebo + Losartan Placebo) Group 2-n=25: BMA concentrate + Fisetin Placebo + Active Losartan Group 3-n=25: BMA concentrate + Active Fisetin + Losartan Placebo Group 4-n=25: BMA concentrate + Active Fisetin + Active Losartan
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Active Fisetin and Active Losartan | Experimental | Drug: Fisetin, Drug: LosartanLosartan 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). |
| Active Fisetin and Losartan Placebo | Active comparator | Drug: Fisetin, Drug: Placebo - LosartanLosartan Placebo 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). |
| Fisetin Placebo and Active Losartan | Active comparator | Drug: Losartan, Drug: Placebo FisetinLosartan 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin Placebo 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). |
| Control | Placebo comparator | Drug: Placebo - Losartan, Drug: Placebo FisetinLosartan placebo 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin Placebo 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91). |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 40 and 85 years of age;
- Ambulatory persons with osteoarthritis (OA) of at least one knee (Kellgren-Lawrence grade II-IV);
- Baseline pain of 3-10 points on the target knee and a pain differential of at least -2 points on the contralateral knee as exhibited by the worst pain score (on the 11-point Numeric Rating Scale) for the previous week.
Key exclusion criteria (36 listed)
- Planned surgery on either the contralateral or target knee at any time during the Study period including dosing and follow-up;
- Within 6 months of signing informed consent has received diagnostic arthroscopy of the target knee or arthroscopic surgery (including microfracture and meniscectomy) on the target knee;
- Within 12 weeks of signing informed consent has received intra-articular treatment of the target knee with steroids or hyaluronic acid derivatives;
- History of previous total or partial arthroplasty in the target knee. Partial or total arthroplasty 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;
- Within 2 years of signing informed consent history of active blood disorders (i.e., DVTs, chronic blood clotting, hemophilia, leukemia, myeloma, etc.); 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FisetinAlso: Novusetin, 7,3',4'-flavon-3-ol, 3,3',4',7-tetrahydroxyflavoneOral Fisetin 20 mg/kg taken for 10 days total. | Drug | Active Fisetin and Active Losartan, Active Fisetin and Losartan Placebo |
| LosartanAlso: Losartan potassium12.5 mg oral Losartan taken for 30 days total. | Drug | Active Fisetin and Active Losartan, Fisetin Placebo and Active Losartan |
| Placebo - LosartanAlso: Placebo Oral CapsuleLosartan appearance-matched microcrystalline cellulose placebo. 12.5 taken for 30 days total. | Drug | Active Fisetin and Losartan Placebo, Control |
| Placebo FisetinAlso: Placebo Oral CapsuleFisetin appearance-matched microcrystalline cellulose placebo. 20 mg/kg taken for 10 days total. | Drug | Control, Fisetin Placebo and Active Losartan |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: Adverse events will be collected from the date of BMAC injection to 12 months after injection
Occurrence of adverse events
19 secondary outcomes
Morphological and Quantitative Magnetic Resonance Imaging (MRI)
Time frame: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection)
Evaluation of patient reported outcome (PRO) for quality of life
Time frame: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Evaluation of patient reported outcome (PRO) for knee functions (WOMAC)
Time frame: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Evaluation of patient reported outcome (PRO) for knee functions (Tegner)
Time frame: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Evaluation of patient reported outcome (PRO) for knee functions (IKDC)
Time frame: within 3 months of injection, 32 days post baseline, 14 days post injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection, 18 months post injection
Patient-Reported Outcome Questionnaires
Time frame: Screening, weekly post 1st study drug dose (pre-injection), weekly post injection (for 4 months)
Change in muscle strength of the study knee
Time frame: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (LEK)
Time frame: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (Stair Test)
Time frame: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection]
Change in physical function of the Study Knee (fast 40-meter walk)
Time frame: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (TUG)
Time frame: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection
Change in physical function of the Study Knee (6-minute walk test)
Time frame: 32 days - 3 months prior to injection, 6 months post injection, 12 months post injection]
Change in associate biomarkers as compared to placebo in peripheral blood plasma/serum
Time frame: screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection
Change in CTX-II as compared to placebo in urine
Time frame: 32 days post baseline, 6 months post injection, 12 months post injection
Change in levels of senescent PBMCS (total and specific PBMC subsets such as T-Cells)
Time frame: screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection
Change in synovial fluid content
Time frame: 32 days post baseline, 6 months post injection, 12 months post injection
Characterization of Bone Marrow Derived Aspirate Concentrate cell content prior to injection
Time frame: 32 days post baseline
Characterization of Bone Marrow Derived plasma biomarkers prior to injection
Time frame: 32 days post baseline
Change in time to conversion to alternative treatment
Time frame: Subjects may receive alternative treatment at any point during the 18-month study, continued participation will be determined on an individual basis (The time to resort to alternative therapy from baseline will be recorded)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johnny Huard, PhD principal investigator
Steadman Philippon Research Institute
Marc Philippon, MD principal investigator
Steadman Philippon Research Institute
Scott L Tashman, PhD principal investigator
Steadman Philippon Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fisetin and Losartan in people with Osteoarthritis, Knee, run by Steadman Philippon Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: Adverse events will be collected from the date of BMAC injection to 12 months after injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.