An Exploratory Clinical Study to Investigate Biomarkers of Senescence in Patients With Osteoarthritis of the Knee

NCT03100799 | Completed

• 1 other identifier: UBX-OA-TNID-0001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. Following imaging, arthrocentesis of both knees and an arthroscopy of the target knee will occur to obtain fluid, synovium and cartilage for analysis.

Conditions

Osteoarthritis, Knee

Keywords

Osteoarthritis; Senescence; Magnetic resonance imaging; Arthroscopy; Arthrocentesis; Biomarker

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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)

  Visit 2 (Day 7) and Visit 3 (Day 14)

• Inter-interval variability of candidate biomarkers of senescence

  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

  Screening (Day 1), Visit 2 (Day 7) and Visit 3 (Day 14)

Other Outcomes (2)

• Correlation between senescence burden (percentage of cells staining positive on IHC) and phenotypic disease data (e.g., Kellgren Lawrence score) in patients with osteoarthritis

  Screening (Day 1), Visit 2 (Day 7) and Visit 3 (Day 14)

• Correlation between synovitis (semi-quantitative scoring of synovium by gadolinium-enhanced MRI) and pain (WOMAC-A as derived from KOOS Knee Survey)

  Screening (Day 1), Visit 2 (Day 7) and Visit 3 (Day 14)

Study Arms (1)

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.

Procedure: Arthroscopy; Procedure: Arthrocentesis; Diagnostic Test: MRI

Interventions

Arthroscopy PROCEDURE

Arthroscopy of the target knee

Patients with osteoarthritis of the knee

Arthrocentesis PROCEDURE

Arthrocentesis of the target knee and contralateral knee (if patient consents)

Patients with osteoarthritis of the knee

MRI DIAGNOSTIC_TEST

MRI with and without a gadolinium-based contrast agent

Also known as: Magnetic resonance imaging

Patients with osteoarthritis of the knee

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Unity Biotechnology, Inc.: lead

Study Sites (1)

The Arthritis Treatment Center

Frederick, Maryland, 21702, United States

Location

Related Publications (5)

• 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.

  PMID: 21187293 BACKGROUND

• KELLGREN 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.

  PMID: 13498604 BACKGROUND

• Altman 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.

  PMID: 3741515 BACKGROUND

• Benjamini 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

• 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.

  PMID: 11840444 BACKGROUND

Related Links

• KOOS Knee Survey

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Arthroscopy; Arthrocentesis; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Orthopedic Procedures; Paracentesis; Specimen Handling; Clinical Laboratory Techniques; Punctures; Therapeutics; Investigative Techniques; Tomography; Diagnostic Imaging

Study Officials

• Nathan Wei, MD

  The Arthritis Treatment Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm, exploratory non-drug, interventional biomarker study in patients with active osteoarthritis to investigate the degree of senescence-associated disease

Study Record Dates

• First Submitted: March 17, 2017
• First Posted: April 4, 2017
• Study Start: March 2, 2017
• Primary Completion: July 10, 2017
• Study Completion: July 10, 2017
• Last Updated: August 1, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)