A Biomarker Stress Test for Detection of Early Osteoarthritis

Study Overview
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Brief Summary
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Veterans have much higher risk of osteoarthritis (OA) then the general population. Knee OA is common among Veterans and is a leading cause of disability. The earliest stages of OA development, where the joint cartilage wears away, is usually painless. By the time Veterans experience symptoms, the OA is typically advanced and there is nothing that can be done except palliation until the joint is replaced with metal and plastic. If there was a blood test to provide early warning of cartilage wear and joint deterioration, Veterans could potentially be treated early enough to slow down or even prevent OA. So far, development of such a blood test has proved elusive. The investigators propose a new method to amplify the signs of cartilage wear in the blood by challenging the affected joint with a walking task. Similar to a cardiac stress test, this walking challenge may help to separate joints at risk from healthy joints. The investigators will also see if this 'OA stress test' can show if a simple and inexpensive load-modifying shoe can improve joint health in Veterans with early knee OA.

Official Title
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A Novel Serum Biomarker Stress Test for Detection of Early Osteoarthritis

Conditions
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Osteoarthritis

Intervention / Treatment
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* Device: Variable-Stiffness Shoe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-80 years symptomatic medial compartment knee OA (KL grades 0-2) full weight-bearing status able to walk for 30 minutes or longer able to undergo MRI scan agreement and ability to use provided shoe as primary walking shoe (4 or more hours a day) during the 6 month study period Exclusion Criteria: inflammatory arthritis, gout or recurrent pseudogout patellofemoral or lateral compartment disease that is equal to or more extensive than medial disease symptomatic OA of other lower extremity joints BMI >35 kg/m2 prior structural surgery of the knee except for medial meniscectomy performed > 6 months prior use of shoe insert or hinged knee brace pes planus, and/or unusual foot size or shape

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Variable-Stiffness Shoe<br>Subjects will wear a load-modifying variable-stiffness shoe for 6 months | Device: Variable-Stiffness Shoe<br>* A load-modifying variable-stiffness shoe previously shown to reduce joint loading<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change at 6 Months From Baseline in First Peak Knee Adduction Moment (KAM): (6 Month Value - Baseline) | Knee adduction moment describes the medial/lateral load distribution of the knee measured while walking in a gait laboratory. Before normalization to account for size, the knee adduction moment is expressed in Nm. However, to account for different sized people, the knee adduction moment is transformed and expressed in percentage of body weight times height (%BW*ht). Higher knee adduction moments have been linked to more severe osteoarthritis (OA). Knee adduction moment will be analyzed at baseline and after 6 months of variable-stiffness shoe wear. Values at 6 months (in variable-stiffness shoe) will be compared to baseline (in control shoe). | Baseline to 6 months | 
| Change at 6 Months From Baseline in Serum COMP Biomarker Levels in Response to a Mechanical Stimulus (6 Month - Baseline) | Serum samples were collected before and after a 30 minute walking activity. Levels of serum cartilage oligomeric matrix protein (COMP) 3.5 hours following the 30-minute walk, expressed as a percentage of pre-activity resting values, were assessed, and values at 6 months were compared to baseline. | Baseline to 6 months |