Effects of an Herbal Topical Cream on Osteoarthritis Symptoms, Biomarkers, and Disease Progression in the Knee
Condition: Osteoarthritis
MeSH terms: Osteoarthritis; Disease Progression
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Arthritis Relief Plus (ARP) Cream is a natural, herbal cream that has been shown to provide
      pain relief and decreased stiffness. Anecdotal reports suggest that pain may continue to be
      reduced months after cream use is stopped, indicating that there could be some
      disease-modifying effects of the cream. The purpose of this study is to test the claim that
      the ARP cream can provide long-term pain relief to osteoarthritis patients after only a short
      period of use. The study will also try to determine whether the pain relief is accompanied
      with any measurable indications that the progression of osteoarthritis has slowed or halted
    

Detailed description: 
      General Procedure: Subjects will be screened for: a history of knee pain and surgery by
      questionnaire; kidney disease as determined by blood creatinine levels; knee diameter less
      than 17cm and body diameter less than 60 cm due to the physical constraints of the MRI. Prior
      X-rays or MRIs will be examined to evaluate the subject's level of OA. X-rays and MRIs that
      are older than 2 years, cannot be used and these potential subjects will receive one set of 2
      knee x-rays prior to enrollment. If they qualify and wish to enroll, they will be matched on
      age, sex and degree of OA and assigned by a 3rd party investigator to either a placebo group
      or active treatment group. Subjects will be asked to complete baseline questionnaires,
      functional tests, and have blood draws and MRI screenings before starting their treatment.
      Enrolled subjects will apply 2.5 grams of active or placebo cream 3 times per day to the skin
      over the affected knee for 12 weeks. Further measurements will be taken periodically
      throughout the course of the study, as detailed below.

      MRI: Subjects will receive MRI scans of the affected knee 3 times: at enrollment, 12 weeks,
      and 15 months. The MRI scan sessions will take place at the Lucas Center for MRI at Stanford
      University. In preparation for the MRI scan, subjects will be required to fill out a standard
      MRI screening form to ensure that there are no conditions that could interfere with the MRI
      imaging or that could make scanning in any way hazardous. During the sessions, subjects will
      lie on the scanner table on their backs with their legs straight. We will scan one knee. The
      time for this scan will be approximately 1 hour. This entire session will take approximately
      1 and 1/2 hours, including setup time.

      Subjects may be asked to receive a small dose of intravenous gadolinium contrast agent,
      administered by Dr. Gold. This is to improve the evaluation of the articular cartilage.

      Questionnaires: Subjects will receive physical activity, pain and function questionnaires at
      enrollment, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks, 20 weeks, 6 months, 9 months, 12
      months, and 15 months. They will also keep a log of use of other pain medicine, such as
      aspirin.

      Blood/Urine Samples: A small amount of blood (2 tablespoons or 30 ml) will be drawn and urine
      collected up to 11 times throughout the investigation to study blood markers of cartilage
      breakdown (COMP, CTX2, Glc-Gal-PYD) and synthesis (PIIANP) as well as inflammation (HA, CRP)
      and joint vascularity (TNF-alpha, IL-6, osteocalcin). Blood creatinine levels will be tested
      at baseline only.

      Functional Testing: Subjects will also participate in functional testing that will include
      walking tests, rising from a chair, and climbing stairs up to 11 times throughout the
      15-month study. The "6-minute Walk" test is a good indicator of cardiovascular capacity. We
      will ask subjects to cover as much ground as possible in 6 minutes at a maintainable pace,
      and will record the distance traveled. The "Get up and Go" test will measure the time it
      takes a subject to rise from a standard chair, walk three meters, turn around, return, and
      sit down again. Subjects will perform 3 trials, and their fastest time will be recorded. The
      "Timed Stair Climb" test will measure the time it takes subjects to climb up and down five
      standardized steps. Subjects will be instructed to ascend and descent as fast as possible
      using the handrails provided. They will perform 3 trials and the fastest time will be
      selected. Walking speed tests offers an indirect way to measure the functional impact of
      pain. We will ask subjects to walk 10 meters at a maximal or a self-selected pace and will
      calculate their walking speeds. They will perform between 3 to 6 trials of each test.

      All tests will be performed in accordance with ACSM guidelines for exercise testing.
    

Intervention name(s): herbal topical cream
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment