for people ages 18 years and up (full criteria)
at San Diego, California and other locations
study started
completion around



There is an urgent public health need to reduce reliance on opioids for effective long-term pain management, particularly in knee osteoarthritis (KOA). This effectiveness trial will compare commonly recommended treatments to reduce pain and functional limitations in KOA.These results will lead to improved patient selection for treatment and inform evidence based guidelines by offering well-tested, effective, non-surgical alternatives.


Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability worldwide, affecting over 30% of older adults. It represents a major global health and economic burden to individuals and society. The rates of KOA have more than doubled in the past 70 years and continue to grow sharply, given increases in life expectancy and population body mass index (BMI). Surgery is often employed to treat KOA, but it is associated with a high rate of persistent pain, and is not a permanent solution. Numerous nonsurgical therapies have been advocated to treat pain in patients with KOA yet are not often used in clinical care. The limited pain relief and functional improvement seen in a subset of knee OA sufferers has led to a high rate of opioid use and disability in this population. The overarching goal of this study is to conduct a sequential parallel group randomized controlled trial (RCT) to evaluate the comparative effectiveness of conservative behavioral and non-opioid pharmacological treatments (Phase 1) and, among those that indicate interest in obtaining further treatment and those not eligible for conservative treatment, the benefits of procedural interventions (Phase 2). This study will also evaluate whether clinical and psychosocial phenotypes predict short- and longer-term treatment response. The results of this study will examine the effectiveness of each tested intervention and provide meaningful information regarding effectiveness across key subgroups of participants.


Knee Osteoarthrosis, Osteoarthritis, Knee Osteoarthritis, Duloxetine Hydrochloride, Duloxetine, Intra-Articular Injection, Nerve Procedure with long acting blocks, Nerve Procedure with nerve ablation, Pain Coping Skills Training, Best Practices, Best Practices + Duloxetine, Intra-Articular Injection (HA+)


You can join if…

Open to people ages 18 years and up

- Meets American College of Rheumatology Classification criteria for knee osteoarthritis

You CAN'T join if...

  • Any inability to complete study procedures, including, but not limited to inadequate resources to mitigate low English language literacy
  • Unstable medical condition that presents as an absolute or relative contraindication for participation (e.g., unstable angina, poorly controlled diabetes mellitus, end stage renal failure, automated implantable cardioverter-defibrillator that cannot be disabled before RFA).
  • Severe untreated bleeding disorder (anticoagulants may be continued during phase II treatments in most patients)
  • Severe vision or hearing impairment or serious cognitive impairment that could interfere with consent or outcome assessment
  • Poorly controlled serious psychiatric condition
  • Active substance abuse
  • Scheduled joint replacement on the affected knee
  • History of unilateral total knee arthroplasty (TKA) with complaints of KOA pain limited to the operated knee
  • Ulcers or an open wound in the region of the index knee


  • University of California San Diego accepting new patients
    San Diego California 92037 United States
  • VA Medical Center San Diego accepting new patients
    San Diego California 92161 United States


accepting new patients
Start Date
Completion Date
Johns Hopkins University
Phase 3 research study
Study Type
Expecting 1800 study participants
Last Updated