Clinical trial NCT00961623: Characterizing Knee Pain and Response to Surgery Using Local Biomarkers
Official title: Characterizing Knee Pain and Response to Surgery Using Local Biomarkers
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Inflammation
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2009-08-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Our study population includes adult males and females presenting to a single orthopaedic surgeon for arthroscopic management of acute or chronic knee pain due to a mechanical derangement discernable by MRI.

Subjects are selected using a probability sampling scheme, such that every knee arthroscopy patient that presents, without exclusionary criteria described above, is offered enrollment in the study. To date, approximately 85% of patients consent to enrollment, with no apparent sampling bias. Additionally, we are using repeated measures (matched random sampling) to evaluate the role of mediators of knee pain, and to assess the potential of utilizing expression profiles to monitor surgical outcome. For example, clinical indicators and biomarker expression profiles taken peri-operatively are compared to those obtained 12 weeks post-operatively in the same subject.

Brief summary: The diagnosis and monitoring of clinically-significant pathologies of the knee remains challenging, and it is unknown why only some injuries become painful or respond to surgical intervention. The limitations of diagnostic magnetic resonance imaging result in arthroscopy that is not always beneficial. Elucidation of biochemical pathways underlying pain in this condition may aid patient selection for surgery and provide pharmacotherapeutic targets. Cytokines or a novel yet uncharacterized protein may be involved in pain following meniscus injury and diagnostic cytokine assay may help physicians differentiate patients that may benefit from arthroscopy from those that may not. Additionally, evaluating post-operative biochemical profiles may provide a method of monitoring surgical outcome and understanding post-operative continuation or remission of pain.

Detailed description: Lavage of the operative and contralateral knee for comparison are performed under anesthesia prior to arthroscopy by the infusion of 10cc sterile saline into the knee joint followed by the immediate withdrawal into the syringe, and storage at -80°C in a tube containing a protease inhibitor. At 12wk post-operative a 10cc lavage is performed on the knee that underwent surgery. Clinical findings for each sample are quantified using gold-standard symptom severity questionnaires.

The specimens will be analyzed for 31 potential biomarkers using a multiplexed immunoassay panel, the results of which will be compared with pre- and post-operative clinical findings and radiographic imaging. Plans do not currently include microarray analysis, but this may be later included.

Eligibility criteria: Inclusion Criteria:

•Adult patients with knee pain (acute or chronic) who had failed conservative treatment and elected for arthroscopic management. Indications for surgery included the presence of mechanical symptoms on history, a physical examination positive for McMurray's maneuver or joint line tenderness or both, absence of severe joint space narrowing on plain radiography, and the presence of grade III signal changes on MRI in an anatomic location consistent with the history and physical examination.

Exclusion Criteria:

* Less than 18 years old.
* Recent (within three months) intra-articular corticosteroid injection and past or current medical history of autoimmune disease (i.e. rheumatoid arthritis).
* In addition, no patients involved in a worker's compensation claim or personal injury litigation were enrolled in the study.

Primary outcomes:
measure: Surgical outcome: pain and functionality
timeFrame: 12-24wk post-operative.
Secondary outcomes:
measure: Expression profiles of inflammatory mediators
timeFrame: 24wk
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Jason L Dragoo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Eric Leroux
role: STUDY_CHAIR
affiliation: Stanford University
name: Amy Wasterlain
role: STUDY_CHAIR
affiliation: Stanford University
name: Gaetano Scuderi, MD
role: PRINCIPAL_INVESTIGATOR
References: