A sequenced-strategy for improving outcomes in patients with knee osteoarthritis pain

PROJECT SUMMARY/ABSTRACT
Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability worldwide, affecting over
30% of older adults and 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 BMI. Surgery is often employed to treat KOA, but it 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. However, stand-alone conservative treatments including non-opioid
medications and joint injections provide only limited pain relief and functional improvement in a subset of knee
OA sufferers. This has led to a high rate of opioid use in this population. The overarching goal of this proposal
is to conduct a sequential parallel group randomized controlled trial (RCT) to rigorously evaluate the
comparative-effectiveness of conservative behavioral and non-opioid pharmacological treatments (Phase I)
and, among non-responders, the benefits of nonsurgical procedural interventions (Phase II) in three inter-
related Aims. Aim 1 will evaluate the effectiveness of individual and combined online cognitive behavioral
therapy (PainTRAINER) and pharmacologic treatment (duloxetine) in improving pain and function for KOA
patients compared to standard of care. Aim 2 will determine if genicular nerve radiofrequency ablation (RFA)
or intra-articular injection of hyaluronic acid and steroid are more effective in improving outcomes than local
anesthetic nerve block or SOC and help establish the role of these interventional treatments in the overall
management of pain in KOA patients. Patients that have failed Phase I treatment will be provided with an
opioid for severe pain management, if appropriate, allowing us to examine the opioid-sparing effects of these
procedures in a subset of participants. Aim 3 will test whether clinical and psychosocial phenotypes predict
short- and long-term treatment response. Our study involves comprehensive and innovative approaches that
have never before been employed in this context, including: a multidisciplinary cadre of investigators
conducting the largest randomized trial to date evaluating behavioral, pharmacotherapy and nonsurgical
procedural interventions for KOA; a stepped-care, factorial design model that allows for more than two dozen
pair-wise treatment comparisons; phenotyping to identify responders and improve selection for each therapy
(i.e. precision medicine), which is expected to refine outcomes and reduce unnecessary interventions. The
results, which will follow pragmatic principles in order to maximize the information provided to stakeholders, will
examine not only the effectiveness of each tested intervention but also provide meaningful information
regarding effectiveness across key subgroups of patients. The knowledge gained will contribute to the
development of translatable therapeutic strategies for the treatment of patients with KOA pain that will lead to
opioid sparing effects.

Grant Number: 5UH3AR077360-05
NIH Institute/Center: NIH
Principal Investigator: Claudia Campbell