Duloxetine for Osteoarthritis

(RELIFE Trial)

Overseen By Sebastian Tomescu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: Duloxetine

Must not be taking: Antidepressants, Thioridazine, CYP1A2 inhibitors

Disqualifiers: Liver disease, Renal impairment, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including some antidepressants, specific antibiotics, and medications like thioridazine. If you're on any of these, you may need to stop them to participate.

How does the drug Duloxetine differ from other treatments for osteoarthritis?

Duloxetine is unique for osteoarthritis treatment because it is primarily an antidepressant that works by affecting neurotransmitters (chemical messengers in the brain) to help reduce pain perception, unlike traditional treatments that focus on reducing inflammation or directly targeting joint pain. ^{1 2 3 4 5}

What is the purpose of this trial?

Knee replacement surgery for osteoarthritis is a commonly performed procedure in Canada with 75,000 of these surgeries performed each year. Success rate for knee replacement surgery is high but more than 20% of patients are still dissatisfied mainly due to reports of ongoing pain. Pain control following knee surgery is important in order to allow patients to engage in recovery and rehabilitation. The current standard of pain management after surgery centers around the use of opioids which is a concerning practice as highlighted by the opioid epidemic. Duloxetine is an antidepressant that has pain relieving properties and it has been studied in patients undergoing knee replacement surgery. Studies to date have not been designed optimally to demonstrate the full effects of opioid dose reduction and the use of duloxetine as a medication following knee replacement surgery. This research study seeks to start duloxetine before surgery, at the recommended therapeutic dose, and for the duration of the early rehabilitation period. If the study is successful, this low-cost medication can improve satisfaction rates and change the standard way the pain management is typically carried out for patients undergoing the knee replacement surgery.

Eligibility Criteria

The RELIFE trial is for individuals with osteoarthritis undergoing total knee replacement surgery. Participants should not have used opioids or antidepressants recently, and must be able to take oral medication. They are excluded if they have chronic pain disorders other than osteoarthritis, a history of substance abuse, or conditions that interfere with the study.

Inclusion Criteria

I have knee osteoarthritis.

I am scheduled for knee replacement surgery on one knee.

I am 50 years old or older.

Exclusion Criteria

Involved in worker's compensation case/law suit (verbally declared by patient)

I am currently taking triptan or lithium.

Lack of patient consent; unlikely to comply with follow-up

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants receive duloxetine 60mg once daily for 2 weeks before surgery

2 weeks

1 visit (in-person) for baseline assessments

Postoperative Treatment

Participants continue duloxetine 60mg once daily for 6 weeks after surgery

6 weeks

3 visits (in-person) at 1, 6, and 12 weeks post-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Assessments at 6 and 12 weeks post-surgery

Treatment Details

Interventions

• Duloxetine

Trial Overview This trial tests whether taking Duloxetine (an antidepressant with pain-relieving properties) before and after knee replacement surgery can reduce the need for opioids during recovery compared to a placebo. The goal is to improve post-surgery satisfaction by optimizing pain management.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Duloxetine 60mg OD for 2 weeks preoperatively then 60mg OD for 6 weeks post-surgery.

Group II: Control Placebo Group 1 Intervention

Placebo OD for 2 weeks preoperatively then OD for 6 weeks post-surgery.

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

Approved in United States as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Approved in European Union as Cymbalta / Yentreve for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Diabetic Peripheral Neuropathic Pain
• Fibromyalgia
• Stress Urinary Incontinence

Approved in Canada as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

References

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

Efficacy of needle-knife combined with etanercept treatment regarding disease activity and hip joint function in ankylosing spondylitis patients with hip joint involvement: A randomized controlled study. [2020]

2. Canada pubmed.ncbi.nlm.nih.gov

Canadian Rheumatology Association Consensus on the use of anti-tumor necrosis factor-alpha directed therapies in the treatment of spondyloarthritis. [2015]

3. Germany pubmed.ncbi.nlm.nih.gov

Effect of etanercept and entecavil in a patient with rheumatoid arthritis who is a hepatitis B carrier: a review of the literature. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Etanercept: in ankylosing spondylitis. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of SLZ and MTX (alone or combination) on the treatment of active sacroiliitis in early AS. [2022]