Creatine, Exercise and Inflammatory Markers in Knee Osteoarthritis
Condition: Osteoarthritis, Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional

Summary: 
      The goal of this research project is to determine the effectiveness of creatine
      supplementation and supported low-load walking exercise for managing systemic inflammatory
      biomarkers and joint symptoms in individuals diagnosed with chronic symptomatic knee
      osteoarthritis. The central hypothesis of this investigation is that creatine supplementation
      and exercise will significantly lower systemic biomarkers of inflammation in patients
      diagnosed with knee osteoarthritis.
    

Detailed description: 
      Participants will provide informed consent, complete participant information and knee
      demographic forms, and undergo radiographic evaluation to confirm eligibility. Baseline
      evaluation of (1) systemic inflammation; and (2) knee joint pain and function will be
      completed. Following baseline evaluation, participants will be randomly assigned to 1 of 3
      groups using online software available at http://www.randomizer.org/:

        1. Exercise group: Participants will exercise for 30 minutes under low-load walking
           conditions 3x per week for 12 consecutive weeks on a Lower Body Positive Pressure (LBPP)
           treadmill (Alter-G Inc - Menlo Park, CA) at a set speed of 3.1 mph at 0⁰ incline. The
           initial five minutes of each exercise session will be used as a warm-up to allow the
           participant to reach their target heart rate, to accommodate to walking on the
           treadmill's belt surface, and to facilitate adjustment of the LBPP within the
           treadmill's air chamber to a percentage of unweighting that eliminates or substantially
           reduces the participant's acute knee pain for the duration of the 30 minute walking
           session. Subjects will be blinded to the amount of LBPP used to un-weight them during
           each low-load walking session.

        2. Creatine group: Participants will supplement their regular diet with creatine
           monohydrate for 12 consecutive weeks. In week #1, participants will ingest 5 grams of
           creatine monohydrate 4x per day for a total ingestion of 20 grams per day. For the
           remaining 11 weeks, participants will consume 5 grams of creatine monohydrate per day to
           maintain the increased concentration of creatine.

        3. Placebo group: Participants in the placebo group will supplement their regular diet with
           maltodextrin (an inert sugar based molecule) for 12 consecutive weeks. In week #1,
           participants will ingest 5 grams of maltodextrin 4x per day for a total ingestion of 20
           grams per day. They will then ingest 5 grams of maltodextrin per day for the remaining
           11 weeks.

      All data collection will take place at the Pan Am Clinic, a multidisciplinary tertiary care
      hospital and research facility that serves as the Winnipeg Regional Health Authority's
      "Centre of Excellence for Musculoskeletal Injury Assessment and Treatment". This project will
      utilize the combined assets of University of Manitoba and Pan Am Clinic to access medical
      resources that are used on a daily basis for the diagnosis, treatment, and long term
      management of patients with knee OA. All participants will undergo follow-up evaluation 13
      weeks after their initial baseline evaluation.

      Aim #1: Determine if knee OA systemic inflammation is significantly decreased following
      completion of a 12 week creatine supplementation or low-load treadmill walking exercise
      regimen.

      Hypotheses:

        -  There will be a significant decrease in systemic inflammation following completion of a
           12 week creatine supplementation program.

        -  There will be a significant decrease in systemic inflammation following completion of a
           12 week low-load walking exercise program.

        -  There will be no decrease in systemic inflammation following completion of a 12 week
           placebo supplementation program.

      Primary Outcome Measures: Systemic inflammation will be evaluated by obtaining venous blood
      samples from the participants. Blood samples (approximately 20 mL) will be drawn by
      venipuncture from the antecubital vein into cooled (4°C) vacutainer tubes containing EDTA
      under sterile conditions. After inversion, tubes will be centrifuged at 1065g for 15 minutes
      at 4°C. Approximately 8 mL of plasma will be aliquoted into Eppendorf tubes (8 x 1 mL per
      tube) and frozen at -80°C until analysis. All plasma samples will be evaluated for C-reactive
      protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and
      interleukin-10 (IL-10) using an enzyme linked immunosorbent assay (ELISA) kit according to
      the manufacturer's instructions. All assays will be analyzed in duplicate within the same
      microplate to reduce variation. Serum will be obtained by drawing a blood sample by
      venipuncture into vacutainer serum separator tubes. This serum will be used to analyze the
      serum cartilage oligomeric matrix protein (sCOMP) using an ELISA kit according to the
      manufacturer's instructions.

      Aim #2: Determine if knee OA joint pain and function are significantly altered following
      completion of a 12 week creatine supplementation or low-load treadmill walking exercise
      regimen.

      Hypotheses:

        -  There will be a significant decrease in knee OA joint pain and dysfunction following
           completion of a 12 week creatine supplementation program.

        -  There will be a significant decrease in knee OA joint pain and dysfunction following
           completion of a 12 week low-load walking exercise program.

        -  There will be no significant decrease in knee OA joint pain and dysfunction following
           completion of a 12 week placebo supplementation program.

      Primary Outcome Measures: Knee pain during normal activities of daily living (ADLs) will be
      evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. The
      KOOS is a self-administered, knee-specific questionnaire that is designed to measure OA
      patient's knee pain over the previous seven-day period. Testing indicates that it is a valid,
      highly reliable and responsive measurement tool for evaluating changes after different OA
      interventions.

      Secondary Outcome Measures: Bilateral knee joint function and physical health will be
      evaluated through the following measures both pre and post study:

        1. Goniometric assessment of knee joint range of motion (ROM) is a clinically accepted
           procedure for evaluating joint function. It allows the reliable and accurate
           quantification of movement using linear (cm) and angular units (degrees).

        2. Isokinetic evaluation of thigh muscle strength is the gold standard method used to
           quantify thigh muscle strength about an OA knee joint in both longitudinal and clinical
           investigations, as well as to examine the effect of creatine or exercise interventions
           on patients with knee OA.

        3. Measurement of cardiovascular (CV) capacity via maximum volume of oxygen uptake (VO2
           max) testing. VO2 max testing assesses the maximum amount of oxygen that a person can
           consume per minute at a maximum work rate and is considered the best measure of
           cardiovascular health.
    

Intervention name(s): Creatine; Walking Exercise; placebo (maltodextrin)
Intervention type(s): Dietary Supplement; Other; Dietary Supplement
Intervention description(s): Subjects will supplement their regular diet with 20 grams of creatine for 1 week and then 5 grams of creatine for the following 11 weeks.; Subjects will walk on a specialized treadmill that lowers the impact of walking by taking up to 80% of their body weight away. The subjects will exercise by walking on this treadmill at 3.1 mph, 3 days per week for 30 minutes per day for 12 weeks.; Subjects will supplement their regular diet with 20 grams of maltodextrin for 1 week and then 5 grams of maltodextrin for the following 11 weeks.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment