Clinical trial NCT01241812: Biomarkers and Knee Osteoarthritis
Official title: Biomarkers and Knee Osteoarthritis: Associations With Joint Load and Effects of Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: knee
osteoarthritis
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Arthritis Network
First posted: 2010-11-16
Enrollment: 17
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: High joint load during walking has been linked to cartilage degradation. Biomarkers, found in the blood and urine, are protein fragments released after cartilage degradation characteristic of OA. They have the potential to enable direct and immediate disease state monitoring and identification of early cartilage changes. Little is known about the association of biomarkers with joint load or if exercise aimed at reducing joint load changes biomarker levels, thus reducing the risk of OA progression. This study will provide novel information on these relationships and will guide future intervention studies. The investigators hypothesize that certain biomarkers will be highly correlated with joint loading during walking and that the levels of these biomarkers in the blood and urine will decrease following an exercise intervention aimed at cartilage unloading.

Detailed description: Participants will be tested twice (baseline and 11 weeks later) where they will undergo gait and strength analyses by the same blinded assessor, complete self-report questionnaires, and have blood and urine samples drawn. Participants will then be randomized into either: (i) exercise; or (ii) usual care (no additional treatment). Those in the exercise group will complete 10-weeks of strengthening targeting lower limb muscles. Once weekly, they will consult with the study physiotherapist (MAH) at UBC to ensure proper performance and safe progression of exercises. Participants will be given cuff weights and resistance bands to complete exercises at home five times per week. Exercise compliance will be monitored using log books. All participants will be encouraged to maintain their usual treatment regimen (except for exercises completed by the exercise group), but will document any unexpected alterations such as medication changes or physician visits.

Eligibility criteria: Inclusion Criteria:

* age greater than 50 years (to meet the American College of Rheumatology clinical definition of OA)
* radiographically confirmed knee OA in the medial compartment of the tibiofemoral joint
* knee pain during walking greater than 3/10 (based on an 11-point scale; 0 = "no pain", 10 = "maximal pain") on most days of the previous month
* predominance of pain/tenderness over the medial (inside) region of the knee

Exclusion Criteria:

* articular cartilage degradation in the lateral tibiofemoral compartment greater than the medial (medial compartment OA is more common than lateral and the KAM is a validated measure of medial compartment loading only)
* currently in a structured exercise program
* medical condition precluding exercise
* inflammatory arthritic condition
* history of knee replacement surgery
* recent use of corticosteroids (oral or via injection)
* unable to attend exercise training sessions at UBC
* pain originating predominantly from the patellofemoral joint
* inability to ambulate without a gait aid
* non-English speaking (questionnaires are in English and must be completed by the study participant only)
* recent (within 6 months) arthroscopic knee surgery
* significant hip or back pain (limits the ability to perform the testing and exercises)

Primary outcomes:
measure: Serum levels of biomarkers (COMP, HA, C2C, CP2) measured at baseline and 11 weeks
timeFrame: 11 weeks
measure: Urinary levels of biomarkers (CTX-2, C2C) measured at baseline and 11 weeks
timeFrame: 11 weeks
Secondary outcomes:
measure: Knee joint loading during walking (external knee adduction moment) measured at baseline and 11 weeks
timeFrame: 11 weeks
measure: Self-reported pain and physical function (WOMAC) measured at baseline and 11 weeks.
timeFrame: 11 weeks
measure: Isometric muscle strength (hamstrings, quadriceps, hip abductors) measured at baseline and 11 weeks
timeFrame: 11 weeks
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Michael A. Hunt, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hunt MA, Pollock CL, Kraus VB, Saxne T, Peters S, Huebner JL, Sayre EC, Cibere J. Relationships amongst osteoarthritis biomarkers, dynamic knee joint load, and exercise: results from a randomized controlled pilot study. BMC Musculoskelet Disord. 2013 Mar 27;14:115. doi: 10.1186/1471-2474-14-115.