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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04504812
Recruitment Status : Recruiting
First Posted : August 7, 2020
Last Update Posted : January 31, 2023
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Johns Hopkins University

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Knee Osteoarthrosis Drug: Duloxetine Combination Product: Intra-Articular Injection Procedure: Nerve Procedure with long acting blocks Procedure: Nerve Procedure with nerve ablation Behavioral: Pain Coping Skills Training Other: Best Practices Phase 3

Detailed Description:
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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2700 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Using a stepped care model, Phase 1 participants will be randomly assigned to minimally invasive treatments, including best practices, best practices plus duloxetine, and best practices plus duloxetine combined with a web-based pain coping skills training program. Those who note interest in additional treatment following completion of Phase 1, as well as those that are not eligible for Phase 1 treatment, will be randomly assigned to more aggressive procedures: intra-articular hyaluronic acid, steroid and local anesthetic injection, or a nerve procedure that would either include a long acting block or nerve ablation.
Masking: Single (Participant)
Masking Description: Individuals randomized to a nerve procedure will be blinded to whether they have a long acting block or nerve ablation.
Primary Purpose: Treatment
Official Title: A Sequenced Strategy for Improving Outcomes in People With Knee Osteoarthritis Pain
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Phase 1: Best Practices
Participants will receive an intervention from the best practices.
 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.
Active Comparator: Phase 1: Best Practices + Duloxetine
Participants will receive Duloxetine in addition to an intervention from the best practices.
 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.
Other Name: Cymbalta

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.
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.
 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.
Other Name: Cymbalta

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.
Active Comparator: Phase 2: Intra-Articular Injection (HA+)
Participants will receive an intra-articular injection of hyaluronic acid mixed with steroid and bupivacaine.
 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.
Active Comparator: Phase 2: Nerve Procedure: Long Acting Blocks
Participants will receive a nerve blocking procedure, long-acting local anesthetic, and steroid injection.
 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.
Active Comparator: Phase 2: Nerve Procedure: Nerve Ablation
Participants will receive a nerve ablation procedure and steroid injection.
 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.


Outcome Measures
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Primary Outcome Measures :
  1. Change in Pain Intensity as assessed by the Modified 4-item BPI Pain Scale [ Time Frame: Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2 ]
    The Modified 4-item BPI Pain scale consists of 3 items from BPI Pain Intensity and 1 item from BPI Pain Interference. This is a continuous measure that will be calculated as the average of worst, average, current knee pain, and pain upon walking.


Secondary Outcome Measures :
  1. Change in Pain Interference as assessed by the BPI [ Time Frame: Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2 ]
    The BPI Pain Interference domain assesses self-reported consequences of pain on relevant aspects of one's life. The BPI measures how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. BPI pain interference is typically scored as the mean of the seven interference items. BPI Interference ranges from 0-10 with higher scores reflecting greater pain interference in activities of daily living.

  2. Change in Physical Functioning as assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2 ]
    The KOOS evaluates function for participants with osteoarthritis of the knee that is related to injury and degeneration. The KOOS short form includes 12 items and measures pain, functional limitation and quality of life. Physical functioning questions cover everyday activities such as rising from sitting, standing getting in and out of the car and twisting/pivoting on the knee. Scores range from 0-100 with lower scores indicating worse knee symptoms.

  3. Patient Global impression of Change (PGIC) [ Time Frame: At 8 weeks post-treatment for Phase 1; At 12 weeks post-treatment for Phase 2 ]
    The PGIC scale evaluates all aspects of participants' health and assesses if there has been an improvement or decline in clinical status. It is a 7-item scale that ranges between "a great deal worse" to "a great deal better." Higher scores reflect greater improvement in clinical status.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04504812


Contacts
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Contact: Claudia Campbell, PhD 888-304-0711 ccampb41@jhmi.edu

Locations
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Sponsors and Collaborators
Johns Hopkins University
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
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Principal Investigator: Steven Cohen, MD Johns Hopkins University
More Information
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04504812    
Other Study ID Numbers: IRB00238678
1UG3AR077360-01 ( U.S. NIH Grant/Contract )
First Posted: August 7, 2020    Key Record Dates
Last Update Posted: January 31, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After last subject enrollment and all follow up procedures have been completed, the Helping to End Addiction Long-Term (HEAL) Pain Management Effectiveness Research Network Data Coordinating Center at the University of Utah will prepare a final study database for the trial, which will then be used for statistical analyses and publication of findings from the trial.The Trial will provide a resource of data concerning methods for managing pain and reducing opioid addiction, and the Data Coordinating Center (DCC) will produce a database that can be used by non- Effectiveness Research Network (ERN) investigators.The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. Data elements that are considered unreliable will be deleted, and this will be noted in the documentation.
Time Frame: These policies are expected to focus primarily on the timing of data release. The investigator's preliminary plan is to release the database (defined below) at the time of publication of the primary manuscript, or within 12 months of last patient procedure, whichever comes first. Implementation of the plan will follow the HEAL Public Access and Data Sharing Policy as outlined at https://heal.nih.gov/about/public-access-data
Access Criteria: Access to the releasable database housed in the NIH-assigned repository will be in accordance with procedures and regulations of the NIH or specific institute. The data coordinating center will not provide any support for investigators using the releasable database.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Duloxetine Hydrochloride
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
 Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antidepressive Agents
Psychotropic Drugs
Dopamine Agents