Post-traumatic Arthritis Associated With Joint Injury

Assessment of Biomarkers Associated With Joint Injury and Subsequent Post-Traumatic Arthritis

Arthritis is the nation's most common cause of disability. An estimated 50 million U.S. adults (about 1 in 5) report doctor-diagnosed arthritis. Twenty three million U.S. adults of working age (18-64 years) have arthritis; and in this age group arthritis-attributable work limitations affect about 1 in 3 people. An estimated 12% of all patients seeking intervention for symptomatic arthritis have an etiology of previous trauma to the involved joint.

The purpose of this study is to examine these inflammatory compounds in the joint fluid (synovial fluid), the joint lining (synovium), and in blood among subjects with isolated intra-articular fractures.

The hypothesis is that early levels of intra-articular inflammation and markers of joint tissue degeneration following articular fracture in the human knee are predictive of the development of PTA (Post Traumatic Arthritis). Early levels of intra-articular inflammation and markers of joint tissue degeneration identified from human knee joints following articular injury are predictive of the development of PTA in the mouse knee.

Samples of blood, urine and synovial fluid will be taken at the spanning frame surgery and only synovial fluid at the ORIF (Open Reduction Internal Fixation)surgery. Two MRIs (Magnetic Resonance Imaging) will be part of this study at 4 weeks and 18 months.Participants will complete a set of questionnaires(KOOS: Knee Injury and Osteoarthritis Outcome Score) at 4 weeks and 18 months.

Study Overview

• Status: Completed
• Conditions: Arthritis
• Intervention / Treatment: Procedure: Tissue sample collection at the time of surgery

Detailed Description

40 patients with a closed unilateral articular fracture of the knee requiring operative treatment will be enrolled over an 18 month period. Tissue samples including synovial fluid from the injured and contralateral knee, serum and urine will be collected pre-operatively at the time of framing and ORIF. If patients only need to have one surgery (ORIF) sample will be collected only once. MRI imaging of the injured knee will be obtained after fixation at between week 6 and 8 and at 18 months. Tissue samples will be analyzed for established biomarkers of joint inflammation and degradation. Patients will be followed for 18 months to assess for signs of post-traumatic arthritis. Imaging with plain film and MRI will occur at 18 months. MRI imaging analysis of cartilage thickness and composition changes will be assessed in the injured knees. Assessment of articular cartilage and joint space narrowing and KOOS will be correlated to biomarkers that may be indicative and predictive of joint degeneration and the development of PTA.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27707
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adults that are at least 18 years old and had a unilateral closed intra articular fracture of the knee that requires surgery.

Description

Inclusion Criteria:

• Subjects will be adult patients (over 18 years old)
• Patients must present with a unilateral closed intra-articular fracture of the knee.

Exclusion Criteria:

• Pre-existing arthritis in the injured or contra-lateral knee,
• Previous total knee replacement
• Active joint infection
• Pathologic fracture
• Active inflammatory arthritis
• Open fracture of the involved knee
• Contra-lateral knee injury
• HIV infection (if previously known)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Single Arm	Procedure: Tissue sample collection at the time of surgery; Spanning surgery; A blood sample (32.5 ml); joint aspirate (removal of synovial fluid) from both knees; urine sample ORIF surgery; Joint aspirate (removal of synovial fluid) from both knees; A blood sample (32.5 ml); Urine Sample If patients only require one surgery, sample will be collected only once.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markers of joint tissue degeneration following articular fracture	Tissue samples will be collected at the time of surgery and they will be taken to Duke Basic Science lab where they will be analyzed.	18 months after Injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
KOOS questionnaire	Participants will be scheduled for an MRI 18 months after surgery and a questionnaire will be completed at that time.	Participants will complete this questionnaire at the 18 month follow up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline at 18 months of the extracellular matrix and morphology of knee cartilage using MRI	Two MRIs will be scheduled for all the study participants at 4 weeks (with a 2-6 weeks window) and at 18 months.	Between week 2 and 6 and at 18 months after definitive fixation

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Steven Olson, MD, Duke University

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: February 13, 2013
• First Posted (Estimate): February 15, 2013

Study Record Updates

• Last Update Posted (Estimate): December 19, 2016
• Last Update Submitted That Met QC Criteria: December 16, 2016
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis
• Other Study ID Numbers: Pro00038254

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No