Pain Medication for Knee Osteoarthritis

(PREDICT Trial)

Overseen By Narina Simonian, BS, CCRC

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Northwestern University

Must not be taking: Cannabinoids, High-dose opioids, SSRIs, others

Disqualifiers: Rheumatoid arthritis, Uncontrolled hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medications, duloxetine and celecoxib, to evaluate their effectiveness in relieving pain for people with knee osteoarthritis. The goal is to predict which patients will respond best to these treatments. Participants will be divided into three groups: one taking duloxetine, one taking celecoxib, and one receiving a placebo (a pill with no active medicine). Individuals who have experienced knee pain most days in the past month and can walk with or without a cane might be suitable candidates. The study involves MRIs, blood tests, and completing questionnaires over approximately 20 weeks. As a Phase 4 trial, this research aims to understand how these FDA-approved and effective treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of any current therapies you are using, like TENs units or glucosamine. However, if you are using high-dose opioids, certain antidepressants, or cannabinoids for knee pain, you may need to stop or adjust those medications to participate.

What is the safety track record for these treatments?

Research has shown that both duloxetine and celecoxib are generally safe for treating knee osteoarthritis.

Studies have found that duloxetine can moderately improve pain and joint function. Most people tolerate this medication well, though some might experience mild side effects like nausea or dry mouth, which usually don't last long.

Celecoxib has also demonstrated effectiveness in alleviating pain and improving movement in people with osteoarthritis. It is considered safe, especially when taken as directed, with research supporting its effectiveness at a 200 mg daily dose. Like duloxetine, celecoxib may cause side effects such as stomach upset or headache, which are usually manageable.

Both medications have been used for other conditions and have a good safety record. Always consult a healthcare provider about any concerns before starting a new treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Duloxetine and Celecoxib for knee osteoarthritis because they offer distinct advantages over typical treatments like NSAIDs and corticosteroids. Duloxetine, primarily an antidepressant, is believed to help manage pain by altering neurotransmitter levels, potentially addressing both pain and mood, which is often impacted by chronic pain conditions. Celecoxib, a COX-2 inhibitor, targets inflammation more specifically than traditional NSAIDs, potentially leading to fewer gastrointestinal side effects. These unique mechanisms make them promising options for improving pain management in knee osteoarthritis.

What evidence suggests that this trial's treatments could be effective for knee osteoarthritis?

In this trial, participants will receive either celecoxib, duloxetine, or a placebo. Research has shown that celecoxib can greatly reduce pain and improve mobility in people with osteoarthritis. Studies have found that celecoxib works better than some other common pain relievers, such as diclofenac. Duloxetine has also helped with pain and movement in knee osteoarthritis, though some studies suggest its benefits might be moderate, requiring further research to confirm its effectiveness. Both treatments appear promising, but celecoxib has consistently shown good results according to the available data. ^{1 3 4 6 7}

Who Is on the Research Team?

Thomas Schnitzer

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for individuals with knee pain from osteoarthritis. Participants will undergo various tests including X-rays, MRIs, and questionnaires at Northwestern University over approximately 20 weeks. Key requirements include having knee osteoarthritis and being able to complete the study activities.

Inclusion Criteria

I am in stable health overall.

I can attend all required clinic visits.

I understand the study's purpose, procedures, benefits, and risks and agree to participate.

Exclusion Criteria

I haven't had injections in my knee with hyaluronic acid or steroids recently.

Any medical condition in that in the investigator's judgement may prevent the individual from completing the study or put the individual at undue risk

In the judgement of the investigator, unable or unwilling to follow protocol instructions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to receive duloxetine, celecoxib, or placebo for two treatment periods

16 weeks

Regular visits for assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Celecoxib
• Duloxetine
• Placebo

Trial Overview The study compares the effectiveness of two medications, Celecoxib and Duloxetine, against a placebo in managing knee osteoarthritis pain. It aims to predict who will benefit from these treatments based on brain-based and clinical assessments.

How Is the Trial Designed?

Group I: Duloxetine Active Control 1 Intervention

Duloxetine 60mg tablet, daily (with an initial and final 7-day titration at 30 mg, daily)

Group II: Celecoxib Active Control 1 Intervention

Celecoxib 200 mg tablet, daily

Group III: Placebo Placebo Group 1 Intervention

Matching placebo tablet, daily

Celecoxib is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Celebrex for:

• Pain relief
• Inflammation
• Osteoarthritis
• Rheumatoid arthritis
• Menstrual cramps
• Colorectal polyps prevention

Approved in European Union as Celebrex for:

• Symptomatic relief in osteoarthritis
• Symptomatic relief in rheumatoid arthritis
• Ankylosing spondylitis
• Acute pain
• Primary dysmenorrhea
• Adenomatous polyposis coli

Approved in Canada as Celebrex for:

• Symptomatic relief of osteoarthritis
• Symptomatic relief of rheumatoid arthritis
• Ankylosing spondylitis
• Acute pain
• Primary dysmenorrhea

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Duloxetine significantly reduces pain intensity and improves function in patients with osteoarthritis knee pain compared to placebo, based on a meta-analysis of three randomized controlled trials involving 1,011 patients.

While duloxetine is effective, it is associated with a higher rate of adverse events compared to placebo, although serious adverse events were not significantly different, indicating it has an acceptable safety profile for managing osteoarthritis pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Duloxetine on Osteoarthritis Knee Pain: A Meta-Analysis of Randomized Controlled Trials. Wang, ZY., Shi, SY., Li, SJ., et al.[2022]

In a study of 353 Japanese patients with knee osteoarthritis, duloxetine significantly reduced pain and improved health-related quality of life compared to placebo over a 14-week period, regardless of prior NSAID use patterns.

Duloxetine consistently led to greater reductions in pain severity and improvements in physical function across all subgroups of prior NSAID users, indicating its efficacy as a treatment option for knee OA pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of duloxetine by prior NSAID use in the treatment of chronic osteoarthritis knee pain: A post hoc subgroup analysis of a randomized, placebo-controlled, phase 3 study in Japan. Enomoto, H., Fujikoshi, S., Tsuji, T., et al.[2019]

Duloxetine significantly reduces knee osteoarthritis pain and improves physical function, as shown in a systematic review of 6 studies with 2059 patients, indicating its efficacy as a treatment option.

Despite its effectiveness, duloxetine did not show a significant difference in serious adverse events compared to placebo, suggesting it may have a similar safety profile, but further well-controlled studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Updated Systematic Review and Meta-analysis of Duloxetine for Knee Osteoarthritis Pain. Chen, B., Duan, J., Wen, S., et al.[2023]

Duloxetine is effective for treating osteoarthritic pain, with 42% to 67% of patients experiencing significant pain relief compared to 26% to 50% for placebo, resulting in a number needed to treat (NNT) of 7.

While duloxetine is generally well-tolerated, common side effects include nausea, fatigue, and constipation, with a number needed to harm (NNH) of 16, 17, and 19 respectively, indicating that while benefits are likely, some patients may experience adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Citrome, L., Weiss-Citrome, A.[2022]

In a 10-week study involving 524 patients with knee osteoarthritis, duloxetine significantly reduced pain and improved physical function compared to placebo when added to NSAID therapy.

While duloxetine was effective, it also led to more side effects like nausea and dry mouth, and patients were more likely to discontinue treatment due to these adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Frakes, EP., Risser, RC., Ball, TD., et al.[2022]

In a study of 353 Japanese patients with knee osteoarthritis, duloxetine (60 mg/day) significantly reduced pain in those with 3 or more painful sites compared to placebo, indicating its efficacy in managing multisite pain.

Duloxetine appears to enhance the function of descending inhibitory pain pathways, which may be dysfunctional in patients experiencing central sensitization, making it a promising analgesic option for those with knee osteoarthritis and widespread pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of duloxetine for multisite pain in patients with knee pain due to osteoarthritis: An exploratory post hoc analysis of a Japanese phase 3 randomized study. Itoh, N., Tsuji, T., Ishida, M., et al.[2021]

Duloxetine significantly reduced knee pain in Japanese patients with osteoarthritis compared to placebo, with an average pain score improvement of -2.57 versus -1.80 over 14 weeks, indicating its efficacy in managing pain.

The treatment was well-tolerated, with common side effects like somnolence and dry mouth, but it did not lead to any significant changes in knee joint mobility or structural abnormalities on X-ray, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled Phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. Uchio, Y., Enomoto, H., Alev, L., et al.[2022]

Adding duloxetine to the usual care for knee osteoarthritis (OA) patients with moderate pain is cost-effective, providing significant health benefits (31 additional quality-adjusted life years per 1,000 subjects) at a reasonable cost of $39,300 per quality-adjusted life year.

Implementing a depression screening strategy before prescribing duloxetine also proves beneficial, yielding 17 additional quality-adjusted life years per 1,000 subjects at a cost of $17,000 per quality-adjusted life year, making it a viable option for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Screening for Depressive Symptoms Help Optimize Duloxetine Use in Knee Osteoarthritis Patients With Moderate Pain? A Cost-Effectiveness Analysis. Lenhard, NK., Sullivan, JK., Ross, EL., et al.[2023]

Duloxetine effectively reduces knee pain in both older (≥65 years) and younger (40-64 years) patients with osteoarthritis, showing significant improvement compared to placebo without age affecting treatment outcomes.

While duloxetine is generally well tolerated, increasing the dose to 120 mg for non-responding patients did not yield additional benefits, and the only notable side effect was dizziness, which was more common in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of duloxetine treatment in older and younger patients with osteoarthritis knee pain: a post hoc, subgroup analysis of two randomized, placebo-controlled trials. Micca, JL., Ruff, D., Ahl, J., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4902402/

Efficacy and Safety of Celecoxib Therapy in Osteoarthritis This meta-analysis indicated that celecoxib treatment (200 mg orally once daily) led to significant improvement in the pain and function of osteoarthritis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6334297/

Cost-effectiveness of generic celecoxib in knee ... In the base case analysis of the high pain cohort (WOMAC 50), celecoxib had an incremental cost-effectiveness ratio (ICER) of $284,630/QALY compared with OTC ...

3. journals.lww.com journals.lww.com/md-journal/fulltext/2016/05170/efficacy_and_safety_of_celecoxib_therapy_in.21.aspx

Efficacy and Safety of Celecoxib Therapy in Osteoarthritis This meta-analysis indicated that celecoxib treatment (200 mg orally once daily) led to significant improvement in the pain and function of osteoarthritis.

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/194523

Efficacy of Rofecoxib, Celecoxib, and Acetaminophen in ... In this study, rofecoxib 25 mg/d provided greater therapeutic benefits than maximal daily doses of 4000 mg/d of acetaminophen in treating patients with OA of ...

5. academic.oup.com academic.oup.com/painmedicine/article/22/2/352/5892885

Meta-analysis Comparing Celecoxib with Diclofenac Sodium ... The meta-analysis indicated that celecoxib reduced pain more effectively than diclofenac sodium in patients with KOA, as evaluated by the VAS score.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8252338/

Efficacy and safety of celecoxib combined with JOINS in ... Efficacy and safety of celecoxib combined with JOINS in the treatment of degenerative knee osteoarthritis: study protocol of a randomized controlled trial.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0378874124011425

Efficacy and safety of SKCPT in patients with knee ... In the SKCPT and celecoxib groups, 83.09% and 84.51% had morning stiffness <30 min, 53.68% and 51.41% had joint crepitus during activity, and ...