A Sequenced Strategy for Improving Outcomes in People With Knee Osteoarthritis Pain

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Meets American College of Rheumatology Classification criteria for knee osteoarthritis.

Exclusion Criteria:

- 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04504812
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Johns Hopkins University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Steven Cohen, MD
Principal Investigator Affiliation	Johns Hopkins University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, NIH
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Knee Osteoarthrosis

Additional Details

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.

Arms & Interventions

Arms

Active Comparator: Phase 1: Best Practices

Participants will receive an intervention from the best practices.

Active Comparator: Phase 1: Best Practices + Duloxetine

Participants will receive Duloxetine in addition to an intervention from the best practices.

Active Comparator: Phase 1:Best Practices + Duloxetine + Pain coping skills

Participants will receive Duloxetine and pain coping skills training in addition to an intervention from the best practices.

Active Comparator: Phase 2: Intra-Articular Injection (HA+)

Participants will receive an intra-articular injection of hyaluronic acid mixed with steroid and bupivacaine.

Active Comparator: Phase 2: Nerve Procedure: Long Acting Blocks

Participants will receive a nerve blocking procedure, long-acting local anesthetic, and steroid injection.

Active Comparator: Phase 2: Nerve Procedure: Nerve Ablation

Participants will receive a nerve ablation procedure and steroid injection.

Interventions

Drug: - Duloxetine

Duloxetine is a drug that is used to improve pain and function in people with knee osteoarthritis (KOA). Duloxetine is approved by the Food and Drug Administration (FDA) for the treatment of depression, anxiety disorder, fibromyalgia, and joint pain. It will be titrated up from 20 or 30mg according to a schedule provided by a study provider.

Combination Product: - Intra-Articular Injection

Intra-Articular Injection is an injection of 3-6 milliliter (mL) hyaluronic acid (HA) mixed with 1mL depo methylprednisolone (a steroid) and 2mL 0.5% bupivacaine (an anesthetic) into the knee.

Procedure: - Nerve Procedure with long acting blocks

People assigned to receive this will have 1mL of a long-acting local anesthetic (a.k.a. liposomal bupivacaine or EXPAREL) and steroid injected into the knee.

Procedure: - Nerve Procedure with nerve ablation

People assigned to receive this will have heat applied to destroy the nerve signaling pain in the knee. Steroid will be administered after the procedure to reduce the risk of neuritis.

Behavioral: - Pain Coping Skills Training

Participants will be provided with a written manual that includes login information for the pain coping skills training website. They will be expected to log into the system weekly, work through the modules, and participate in skills practice. This intervention will be conducted in combination with best practices and duloxetine.

Other: - Best Practices

Best Practice includes treatments that experts recommend for knee arthritis pain. Best Practice can include topical or oral pain relievers, a structured exercise program, and weight management if BMI is over 30. Other non-invasive treatments such as acupuncture and yoga are also included.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Alabama, Birmingham, Alabama

Status

Recruiting

Address

University of Alabama

Birmingham, Alabama, 35233

Site Contact

Research Coordinator

Clinical Trial Finder