Osteoarthritis, KneeNCT03100799
An Exploratory Clinical Study to Investigate Biomarkers of Senescence in Patients With Osteoarthritis of the Knee
A study testing Arthroscopy, Arthrocentesis and MRI in people with Osteoarthritis, Knee, run by Unity Biotechnology, Inc. at 1 site in United States.
Trial summary
This is an exploratory non-drug, interventional biomarker study in approximately 30 eligible patients with active osteoarthritis to investigate the degree of senescence-associated disease. Patients will provide blood and urine and undergo MRI imaging with and without gadolinium enhancement. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- Arthroscopy, Arthrocentesis and MRI
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Mar 2017to 10 Jul 2017
- Phase
- Interventional
- 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 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be diagnosed as having primary (idiopathic) femoro-tibial osteoarthritis (OA) of the knee as defined by a modified version of the American College of Rheumatology Criteria (modified clinical and laboratory criteria) for at least 6 months.
- Kellgren-Lawrence (KL) score of grade 1 to 4 inclusive based on a standardized, semi-fixed, weight-bearing radiograph of the knee.
- Adults of age ≥ 35 years
- Body Mass Index less than or equal to an upper limit of 35 kg/m2
- Patients who are able to commit the time required to attend all study visits
- Normal clinical laboratory results with no clinically significant organ dysfunction which, in the opinion of the investigator, would preclude patient from entering the study
Who cannot join
- Any 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
- Prior open knee surgery to the target knee including but not limited to Anterior Cruciate Ligament Repair
- Patients who have had prior arthroscopy and intraarticular treatments for the management of osteoarthritis such as administration of hyaluronic acid or corticosteroids within the last 6 months
- Patients with traumatic knee injury who are scheduled for arthroscopic repair procedures to either target or non-target knee
- Patients who are deemed to be at risk of acute renal insufficiency of any severity due to hepato-renal syndrome or who are in the peri-operative liver transplant period.
- Patients with Diabetes Mellitus.
Show all 40Show fewer
- Patients with renal dysfunction as defined by a Glomerular Filtration Rate <60 ml/min/1.73m2 by laboratory testing.
- Known allergic or hypersensitivity reaction to gadolinium-based contrast agents or patients who have other contraindications for MRI
- Patients requiring anticoagulation therapy other than low dose (81 mg or less) aspirin
- Treatment with an unapproved investigational therapeutic agent and/or experimental therapeutic procedure on the target knee within 24 weeks prior to screening
- Any active known or suspected systemic autoimmune disease Permitted on Study
- vitiligo
- residual hypothyroidism due to autoimmune condition only requiring hormone replacement
- psoriasis not requiring systemic treatment for 2 years
- conditions not expected to recur in the absence of an external trigger Excluded on Study
- documented history of inflammatory bowel disease (including ulcerative colitis and Crohn's disease)
- symptomatic autoimmune conditions (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma])
- systemic lupus erythematosus
- autoimmune vasculitis (e.g. Wegener's Granulomatosis)
- patients with motor neuropathy considered of autoimmune origin (e.g. Guillain-Barré Syndrome)
- History of previous surgery (Total or Partial Knee Replacement) on the Target knee
- Lesions at the planned site of arthroscopy which would present a contraindication to the procedure such as open wounds or infection of the skin
- Any known active infection, including suspicion of intra-articular infection and/or infections that may compromise the immune system such as HIV, Hepatitis B or Hepatitis C infection
- History of sarcoma and/or history of other active malignancy within the last 5 years, except basal cell carcinoma, carcinoma in situ of the cervix and squamous cell carcinoma of the skin
- Secondary osteoarthritis, including:
- Joint dysplasias
- Crystal-induced arthropathy (gout, calcium pyrophosphate deposition disease)
- Aseptic osteonecrosis
- Acromegaly
- Paget's disease
- Ehlers-Danlos Syndrome
- Gaucher's disease
- Stickler's syndrome
- Joint infection
- Hemophilia
- Hemochromatosis
- Neuropathic arthropathy of any cause
- Patients with risk factors for OA of the knee (e.g.: obesity, meniscectomy) are not considered as having secondary OA and can be included in this study
- Female patients who are pregnant. Female patients who are breast-feeding are eligible for enrollment providing the patient agrees not to breast-feed for 24 hours after receiving gadolinium for GE-MRI. Female patients of child-bearing potential must agree to utilize adequate contraceptive measures during the course of the study.
- Patients who do not have the legal capacity or medical competency to provide consent; consent via legally authorized representative is not accepted.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Arthritis Treatment Center
Frederick, Maryland, 21702
About this study
Official title: An Exploratory Clinical Study to Investigate Biomarkers of Senescence in Patients With Mild, Moderate and Severe Osteoarthritis of the Knee
This is an exploratory non-drug, interventional biomarker study in approximately 30 eligible patients with active osteoarthritis to investigate the degree of senescence-associated disease. Patients will provide blood and urine and undergo MRI imaging with and without gadolinium enhancement. Following imaging, arthrocentesis of both knees and an arthroscopy of the target knee will occur to obtain fluid, synovium and cartilage for analysis.
Read the detailed description
This is an exploratory non-drug, interventional, hypothesis generating biomarker study. No Investigational Product will be administered in the study, however, there are study related procedures which are interventional such as arthroscopy, arthrocentesis and infusion of a gadolinium-containing contrast agent.
Consented patients who meet the selection criteria undergo MRI imaging with and without gadolinium contrast of both knees. Approximately seven days following the MRI imaging, patients undergo an arthrocentesis of both knees to obtain synovial fluid and then an arthroscopy of the target knee to obtain synovial and non-weight bearing cartilage tissues.
The patient will return to the clinic approximately seven days following the arthroscopy and arthrocentesis procedures for a routine safety follow-up.
- Conditions
- Osteoarthritis, Knee
- Being tested
- Arthroscopy, Arthrocentesis, MRI
- Keywords
- Osteoarthritis, Senescence, Magnetic resonance imaging, Arthroscopy, Arthrocentesis, Biomarker
- 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.
ArthroscopyProcedure or surgery
Arthroscopy of the target knee
ArthrocentesisProcedure or surgery
Arthrocentesis of the target knee and contralateral knee (if patient consents)
MRIDiagnostic test
Also called Magnetic resonance imaging
MRI with and without a gadolinium-based contrast agent
| Study group | Role | What they receive |
|---|---|---|
| Patients with osteoarthritis of the knee | Other | This is an exploratory non-drug, interventional biomarker study, however, there are study related procedures which are interventional such as arthroscopy, arthrocentesis and MRI assessment with infusion of a gadolinium-contrast agent. Receives: Procedure: Arthroscopy; Procedure: Arthrocentesis; Diagnostic Test: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of synovial senescence as defined by the percentage of cells staining positive for candidate molecular markers of senescence on IHC in patients with osteoarthritis
Percentage of cells staining positive for candidate molecular markers of senescence on IHC
Measured: Study Visit 3 (Day 14)
Secondary outcomes (4)
Concentration of candidate biomarkers in serum, plasma, and urine and correlate with concentration in synovial fluid include but not limited to p16, p21, IL6
Correlation between candidate biomarkers in serum or plasma and urine with synovial fluid biomarkers
Measured: Screening (Day 1) and Visit 3 (Day 14)
Correlation between senescence burden in synovial tissue (percentage of cells staining positive om IHC) and synovitis (semi-quantitative scoring of synovium by gadolinium-enhanced MRI)
Relationship between the synovial senescence, synovitis via biopsy samples and synovitis using gadolinium-enhanced MRI
Measured: Visit 2 (Day 7) and Visit 3 (Day 14)
Inter-interval variability of candidate biomarkers of senescence
Inter-interval variability of candidate biomarkers of senescence
Measured: Screening (Day 1) and Visit 3 (Day 14)
Correlation between degree of synovitis (semi-quantitative scoring of synovium by gadolinium-enhanced MRI) with concentration of biomarkers in plasma or synovial fluid
To determine the relationship between GE-MRI-based assessment of synovium and plasma or synovial candidate biomarkers
Measured: Screening (Day 1), Visit 2 (Day 7) and Visit 3 (Day 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start2 Mar 2017
- Primary completion10 Jul 2017
- Study completion10 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, exploratory non-drug, interventional biomarker study in patients with active osteoarthritis to investigate the degree of senescence-associated disease
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nathan Wei, MD, Principal investigator, The Arthritis Treatment Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03100799
- Sponsor's protocol ID
- UBX-OA-TNID-0001
- Status last verified
- May 2017
- First submitted
- 17 Mar 2017
- Last updated
- 1 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Guermazi A, Roemer FW, Hayashi D, Crema MD, Niu J, Zhang Y, Marra MD, Katur A, Lynch JA, El-Khoury GY, Baker K, Hughes LB, Nevitt MC, Felson DT. Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study. Ann Rheum Dis. 2011 May;70(5):805-11. doi: 10.1136/ard.2010.139618. Epub 2010 Dec 27.
PubMed 21187293KELLGREN JH, LAWRENCE JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957 Dec;16(4):494-502. doi: 10.1136/ard.16.4.494. No abstract available.
PubMed 13498604Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.
PubMed 3741515Benjamini Y, Hochberg Y. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 1995;57(1):289-300.
Kraus VB, Huebner JL, Fink C, King JB, Brown S, Vail TP, Guilak F. Urea as a passive transport marker for arthritis biomarker studies. Arthritis Rheum. 2002 Feb;46(2):420-7. doi: 10.1002/art.10124.
PubMed 11840444
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study to Investigate Biomarkers of Senescence in Patients With Mild, Moderate and Severe Osteoarthritis of the Knee
- ClinicalTrials.gov ID
- NCT03100799
- Acronym / sponsor ID
- UBX-OA-TNID-0001
- Conditions
- Osteoarthritis, Knee
- Keywords
- Osteoarthritis, Senescence, Magnetic resonance imaging, Arthroscopy, Arthrocentesis, Biomarker
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Unity Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 10 Jul 2017 (actual)
- Study completion
- 10 Jul 2017 (actual)
- First posted
- 4 Apr 2017 (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 an exploratory non-drug, interventional biomarker study in approximately 30 eligible patients with active osteoarthritis to investigate the degree of senescence-associated disease. Patients will provide blood and urine and undergo MRI imaging with and without gadolinium enhancement. Following imaging, arthrocentesis of both knees and an arthroscopy of the target knee will occur to obtain fluid, synovium and cartilage for analysis.
Detailed description
This is an exploratory non-drug, interventional, hypothesis generating biomarker study. No Investigational Product will be administered in the study, however, there are study related procedures which are interventional such as arthroscopy, arthrocentesis and infusion of a gadolinium-containing contrast agent.
Consented patients who meet the selection criteria undergo MRI imaging with and without gadolinium contrast of both knees. Approximately seven days following the MRI imaging, patients undergo an arthrocentesis of both knees to obtain synovial fluid and then an arthroscopy of the target knee to obtain synovial and non-weight bearing cartilage tissues.
The patient will return to the clinic approximately seven days following the arthroscopy and arthrocentesis procedures for a routine safety follow-up.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, exploratory non-drug, interventional biomarker study in patients with active osteoarthritis to investigate the degree of senescence-associated disease
| Arm | Type | Receives |
|---|---|---|
| Patients with osteoarthritis of the knee | Other | Procedure: Arthroscopy, Procedure: Arthrocentesis, Diagnostic Test: MRIThis is an exploratory non-drug, interventional biomarker study, however, there are study related procedures which are interventional such as arthroscopy, arthrocentesis and MRI assessment with infusion of a gadolinium-contrast agent. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must be diagnosed as having primary (idiopathic) femoro-tibial osteoarthritis (OA) of the knee as defined by a modified version of the American College of Rheumatology Criteria (modified clinical and laboratory criteria) for at least 6 months.
- Kellgren-Lawrence (KL) score of grade 1 to 4 inclusive based on a standardized, semi-fixed, weight-bearing radiograph of the knee.
- Adults of age ≥ 35 years
- Body Mass Index less than or equal to an upper limit of 35 kg/m2
- Patients who are able to commit the time required to attend all study visits
Key exclusion criteria (40 listed)
- Any 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
- Prior open knee surgery to the target knee including but not limited to Anterior Cruciate Ligament Repair
- Patients who have had prior arthroscopy and intraarticular treatments for the management of osteoarthritis such as administration of hyaluronic acid or corticosteroids within the last 6 months
- Patients with traumatic knee injury who are scheduled for arthroscopic repair procedures to either target or non-target knee
- Patients who are deemed to be at risk of acute renal insufficiency of any severity due to hepato-renal syndrome or who are in the peri-operative liver transplant period.
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 |
|---|---|---|
| ArthroscopyArthroscopy of the target knee | Procedure or surgery | Patients with osteoarthritis of the knee |
| ArthrocentesisArthrocentesis of the target knee and contralateral knee (if patient consents) | Procedure or surgery | Patients with osteoarthritis of the knee |
| MRIAlso: Magnetic resonance imagingMRI with and without a gadolinium-based contrast agent | Diagnostic test | Patients with osteoarthritis of the knee |
Primary outcome
Degree of synovial senescence as defined by the percentage of cells staining positive for candidate molecular markers of senescence on IHC in patients with osteoarthritis
Time frame: Study Visit 3 (Day 14)
Percentage of cells staining positive for candidate molecular markers of senescence on IHC
4 secondary outcomes
Concentration of candidate biomarkers in serum, plasma, and urine and correlate with concentration in synovial fluid include but not limited to p16, p21, IL6
Time frame: Screening (Day 1) and Visit 3 (Day 14)
Correlation between senescence burden in synovial tissue (percentage of cells staining positive om IHC) and synovitis (semi-quantitative scoring of synovium by gadolinium-enhanced MRI)
Time frame: Visit 2 (Day 7) and Visit 3 (Day 14)
Inter-interval variability of candidate biomarkers of senescence
Time frame: Screening (Day 1) and Visit 3 (Day 14)
Correlation between degree of synovitis (semi-quantitative scoring of synovium by gadolinium-enhanced MRI) with concentration of biomarkers in plasma or synovial fluid
Time frame: Screening (Day 1), Visit 2 (Day 7) and Visit 3 (Day 14)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Background: PubMed 21187293Guermazi A, Roemer FW, Hayashi D, Crema MD, Niu J, Zhang Y, Marra MD, Katur A, Lynch JA, El-Khoury GY, Baker K, Hughes LB, Nevitt MC, Felson DT. Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study. Ann Rheum Dis. 2011 May;70(5):805-11. doi: 10.1136/ard.2010.139618. Epub 2010 Dec 27.
- Background: PubMed 13498604KELLGREN JH, LAWRENCE JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957 Dec;16(4):494-502. doi: 10.1136/ard.16.4.494. No abstract available.
- Background: PubMed 3741515Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.
- BackgroundBenjamini Y, Hochberg Y. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 1995;57(1):289-300.
- Background: PubMed 11840444Kraus VB, Huebner JL, Fink C, King JB, Brown S, Vail TP, Guilak F. Urea as a passive transport marker for arthritis biomarker studies. Arthritis Rheum. 2002 Feb;46(2):420-7. doi: 10.1002/art.10124.
- KOOS Knee SurveyLink provided by the sponsor.
- 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.
Nathan Wei, MD principal investigator
The Arthritis Treatment Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arthroscopy, Arthrocentesis and MRI in people with Osteoarthritis, Knee, run by Unity Biotechnology, Inc. 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 6 inclusion and 40 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: finished, as of the sponsor's last update on 1 Aug 2017. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Degree of synovial senescence as defined by the percentage of cells staining positive for candidate molecular markers of senescence on IHC in patients with osteoarthritis (time frame: Study Visit 3 (Day 14)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03100799, which also lists 5 linked publications.
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 1 Aug 2017.