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 is a clinical trial of people who have pain due to knee osteoarthritis at Northwestern University Feinberg School of Medicine. The study will last for about 20 weeks. 180 qualified participants will be randomly assigned in a 1:1:1 ratio (60 participants per group) to one of three treatment groups: duloxetine, celecoxib, or placebo. Participants will have an Xray, knee MRI, brain MRI, blood draws, pain sensitivity testing, and asked to fill out questionnaires. The purpose of this study is to try to predict which participants will respond to the treatment.

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.

Is duloxetine safe for treating knee osteoarthritis pain?

Research shows that duloxetine has been studied for safety in treating knee osteoarthritis pain, and it is generally considered safe for use in humans, though older patients may have a higher risk of side effects due to age-related changes. ^{1 2 3 4 5}

How is the drug combination of Celecoxib and Duloxetine unique for treating knee osteoarthritis?

The combination of Celecoxib and Duloxetine is unique because Duloxetine is a centrally acting analgesic that not only helps with knee osteoarthritis pain but also addresses depression, which can be common in chronic pain conditions. This dual action can be particularly beneficial for patients who experience both pain and depressive symptoms. ^{1 5 6 7 8}

What data supports the effectiveness of the drug duloxetine for knee osteoarthritis pain?

Research shows that duloxetine can significantly reduce pain and improve quality of life for people with knee osteoarthritis, especially when used alongside other pain medications like NSAIDs (nonsteroidal anti-inflammatory drugs). ^{2 5 7 8 9}

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

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

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

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 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]

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]

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]

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 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]

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]

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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

An Updated Systematic Review and Meta-analysis of Duloxetine for Knee Osteoarthritis Pain. [2023]

2. United States 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. [2023]

3. Japan 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. [2019]

4. England 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. [2022]

5. Japan 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. [2021]

6. England 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. [2021]

7. New Zealand 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. [2022]

8. England 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? [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Duloxetine on Osteoarthritis Knee Pain: A Meta-Analysis of Randomized Controlled Trials. [2022]