Duloxetine Combined With Intra-articular Injection of Corticosteroid and Hyaluronic Acid Reduces Pain in the Treatment of Knee Osteoarthritis Patients

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04117893

Collaborator

(none)

150

Enrollment

Location

Arms

25.6

Anticipated Duration (Months)

5.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Intra-articular injection of corticosteroid and hyaluronic acid is a common treatment for osteoarthritis of the knee. As a treatment drug for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of osteoarthritis and improve the function of the knee joint. However, there is no evidence regarding the efficacy of Intra-articular injection of corticosteroid and hyaluronic acid combined with duloxetine for pain management in patients with knee osteoarthritis. The aim of the study was to test the hypothesis that Intra-articular injection of corticosteroid plus hyaluronic acid combined with duloxetine could achieve superior pain management effects to Intra-articular injection of corticosteroid plus hyaluronic acid alone in patients undergoing knee osteoarthritis pain.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee Chronic Pain	Drug: Duloxetine Drug: intra-articular injection of corticosteroid and hyaluronic acid	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

This is a prospective, randomized, open-label blind endpoint (PROBE) study

Primary Purpose:

Treatment

Official Title:

Duloxetine Combined With Intra-articular Injection of Corticosteroid and Hyaluronic Acid Reduces Pain in the Treatment of Knee Osteoarthritis Patients

Actual Study Start Date :

Oct 12, 2020

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duloxetine combined with intra-articular injection	Drug: Duloxetine Participants will start on duloxetine 30 mg per day for one week and then titrated up to duloxetine 60mg per day for 23 weeks. Drug: intra-articular injection of corticosteroid and hyaluronic acid Participants will receive a 3.5 ml intra-articular injection of 30mg of hyaluronic acid plus 10mg of triamcinolone acetonide.
Active Comparator: Intra-articular injection	Drug: intra-articular injection of corticosteroid and hyaluronic acid Participants will receive a 3.5 ml intra-articular injection of 30mg of hyaluronic acid plus 10mg of triamcinolone acetonide.

Arm

Intervention/Treatment

Experimental: Duloxetine combined with intra-articular injection

Drug: Duloxetine

Participants will start on duloxetine 30 mg per day for one week and then titrated up to duloxetine 60mg per day for 23 weeks.

Drug: intra-articular injection of corticosteroid and hyaluronic acid

Participants will receive a 3.5 ml intra-articular injection of 30mg of hyaluronic acid plus 10mg of triamcinolone acetonide.

Active Comparator: Intra-articular injection

Drug: intra-articular injection of corticosteroid and hyaluronic acid

Participants will receive a 3.5 ml intra-articular injection of 30mg of hyaluronic acid plus 10mg of triamcinolone acetonide.

Outcome Measures

Primary Outcome Measures

Weekly mean of the 24h average pain scores [Twenty-fourth weeks]
Weekly mean of the 24h average pain scores in participants with osteoarthritis knee pain at the end of 24 weeks as reported in participants' diaries based on the 11-point Likert scale (an ordinal scale with 0 indicating 'no pain', and 10 indicating 'worst pain imaginable')

Secondary Outcome Measures

The response to treatment [At weeks 1, 2, 4, 8, 16 and 24 post-injection]
The response to treatment defines as a 30% and a 50% reduction of weekly mean score in 24-h average pain severity ratings from baseline to endpoint at weeks1,2,4,8,16 and 24 post-injection.
The Brief Pain Inventory [At weeks 1, 2, 4, 8, 16 and 24 post-injection]
This is a self-reported scale that will use to measure the severity of pain and the interference of pain on function at weeks 1, 2, 4, 8, 16 and 24 post-injection. The severity of the pain was assessed by four questions: participants were rated on their most severe pain, their least severe pain, their average pain over the past 24 hours, and their current pain. The pain scale range from 0(no pain) to 10（extreme pain）. In the past 24 hours, seven questions assessed the impact of pain on daily activities, mood, walking ability, working normally, relationships with others, sleep and pleasure in life. The interference level ranges from 0(no interference) to 10(complete interference), and the average of the interference terms is obtained as a summary interference measurement.
The Western Ontario and McMaster Universities Osteoarthritis Index [At weeks 1, 2, 4, 8, 16 and 24 post-injection]
This instrument is designed to assess pain, stiffness, and physical function in participants with osteoarthritis of the knee and will be evaluate at weeks 1, 2, 4, 8, 16 and 24 post-injection. It consists of 24 questions: 5 on pain, 2 on stiffness, and 17 on physical function, each answered using a 5-point scale ranging from 0 (none) to 4 (extreme). Higher scores on the Western Ontario and McMaster Universities Osteoarthritis Index indicate worse pain, stiffness and functional limitations.
The Patient Global Impression of Improvement Scale [At weeks 2, 4, 8, 16 and 24 post-injection]
A patient-rated 7-point scale of symptomatic improvement, was assessed at all visits starting 2 weeks after treatment. On the The Patient Global Impression of Improvement Scale, a rating of 1 indicates that the participant is 'very much improved', a rating of 4 indicates that the participant has experienced 'no change', and a rating of 7 indicates that the participant is 'very much worse'. which range from 1 to 7.
Hospital Anxiety and Depression Scale [At weeks 2, 4, 8, 16 and 24 post-injection]
This self-rating patient-reported outcome measure will be developed to assess depression and anxiety in patients. Responses are rated on a 4-point Likert scale and range from 0 to 3, with higher scores indicating higher severity.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants meet American College of Rheumatology clinical and radiographic criteria for the diagnosis of knee osteoarthritis with knee pain [ pain for ≥14 days of each month for ≥3 months before study entry, with a mean score ≥4 on the 24-h average pain score (0-10) using the average of daily ratings before the trial]
Body mass index < 40 kg/m2
Radiographic criteria included Kellgren-Lawrence grade Ⅱ-III
Knee stability, no deformity, no lumbar spondylosis with radiculopathy.
Good cognition, and the ability to understand the study protocol and the agreement to participate.

Exclusion Criteria:

Inflammatory arthritis, autoimmune disorder, septic arthritis, or any other concomitant disease (such as liver and kidney disease)
Those who prior synovial ﬂuid analysis indicative of a diagnosis other than osteoarthritis
Participants with contraindications to duloxetine (currently using monoamine oxidase inhibitors, poorly controlled angle-closure glaucoma), previous exposure to duloxetine, combined with other drugs acting on the central nervous system (such as benzodiazepines) and allergic to any of the medications used in this study.
With metabolic diseases or anticoagulation therapy
Participants who had received invasive treatments to the knee during the past 6 months; joint replacement of the knee at any time or current infection in the affected limb.