Exercise + Duloxetine for Knee Osteoarthritis
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Maryland, Baltimore
Must not be taking: Duloxetine, Antipsychotics, Benzodiazepines, Opioids
Disqualifiers: Cognitive impairment, Bipolar, Substance abuse, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests a treatment combining duloxetine and aerobic exercise for adults with knee osteoarthritis and depression. Duloxetine helps manage pain and mood, making it easier for patients to stick to their exercise routine. Duloxetine, an anti-depressant medication, has been recently approved for managing knee osteoarthritis and has shown effectiveness in reducing pain and improving function in patients with osteoarthritis.
Will I have to stop taking my current medications?
The trial requires that you stop taking duloxetine, antipsychotics, benzodiazepines, or opioid pain medications before participating.
What data supports the effectiveness of the drug duloxetine for knee osteoarthritis?
Research shows that duloxetine can help reduce pain in people with knee osteoarthritis, as it has been effective in treating pain from various chronic conditions, including osteoarthritis.
12345Is the combination of exercise and duloxetine safe for humans?
Duloxetine has been studied for safety in various conditions, including knee osteoarthritis and major depressive disorder. In these studies, some people stopped using it due to side effects like weight gain, but most found it tolerable. Exercise is generally safe for most people, but it's always best to consult with a healthcare provider before starting any new treatment.
23678How does the treatment of exercise combined with the drug duloxetine differ from other treatments for knee osteoarthritis?
This treatment is unique because it combines aerobic exercise, which helps improve joint function and reduce pain, with duloxetine, a medication that can help manage pain and improve mood, offering a dual approach to managing knee osteoarthritis symptoms.
910111213Eligibility Criteria
This trial is for English-speaking adults over 40 with knee osteoarthritis and depression, who can do aerobic exercise but aren't currently exercising twice a week or more. They shouldn't be planning knee surgery within six months, have cognitive issues, unstable heart conditions, severe hypertension, certain leg diseases, or be pregnant.Inclusion Criteria
I am 40 years old or older.
English speaking
I have been diagnosed with major depressive disorder.
+3 more
Exclusion Criteria
I cannot safely do supervised exercise due to my current health issues.
Substance abuse disorder or suicidal ideation within the previous year
Pregnant or lactating women
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a combination of aerobic exercise and duloxetine for the treatment of symptomatic knee osteoarthritis and comorbid depression
24 weeks
Weekly exercise sessions, medication titration visits as needed
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests adding the drug Duloxetine to an aerobic exercise program for treating knee osteoarthritis and depression in adults. Everyone gets both treatments; first checking if it's feasible then doing a pilot test to see how well it works.
1Treatment groups
Experimental Treatment
Group I: Aerobic exercise plus DuloxetineExperimental Treatment2 Interventions
Participants will have a starting duloxetine dosage of 30 mg/day and be titrated up to a daily optimal dosage of 60 mg/day as tolerated during the first 12-weeks of the study. Twelve weeks after the receipt of their prescription, participants will be evaluated for the need to increase medication dosage to 90 mg/day. After duloxetine initiation, participants will be provided an exercise prescription that includes a progressive walking program aiming to achieve 50 minutes of moderate-intensity physical activity, three times per week, over 24 weeks.
Aerobic exercise is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Aerobic Exercise for:
- Rehabilitation after stroke
- Improvement of physical function
- Enhancement of cognitive function
- Reduction of depression
🇪🇺 Approved in European Union as Aerobic Exercise for:
- Cardiovascular rehabilitation
- Improvement of physical function
- Enhancement of cognitive function
🇨🇦 Approved in Canada as Aerobic Exercise for:
- Rehabilitation after stroke
- Improvement of physical function
- Enhancement of cognitive function
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Maryland School of MedicineBaltimore, MD
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Who Is Running the Clinical Trial?
University of Maryland, BaltimoreLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Does Screening for Depressive Symptoms Help Optimize Duloxetine Use in Knee Osteoarthritis Patients With Moderate Pain? A Cost-Effectiveness Analysis. [2023]Duloxetine is a treatment approved by the US Food and Drug Administration for both osteoarthritis (OA) pain and depression, though uptake of duloxetine in knee OA management varies. We examined the cost-effectiveness of adding duloxetine to knee OA care in the absence or presence of depression screening.
An Updated Systematic Review and Meta-analysis of Duloxetine for Knee Osteoarthritis Pain. [2023]We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee osteoarthritis (OA) pain.
A randomized, double-blind, placebo-controlled Phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. [2022]To examine the efficacy and safety of duloxetine in Japanese patients with knee pain due to osteoarthritis.
Duloxetine use in chronic painful conditions--individual patient data responder analysis. [2022]Duloxetine has been studied in four distinct chronic pain conditions - osteoarthritis (OA), fibromyalgia, chronic low back pain (CLBP) and diabetic peripheral neuropathic pain (DPNP). These trials have involved large numbers of patients with at least moderate pain, and have used similar methods for recording pain intensity, over about 12 weeks.
The short-term effect and safety of duloxetine in osteoarthritis: A systematic review and meta-analysis. [2022]Previous clinical trials indicated that duloxetine may be effective in the treatment of osteoarthritis (OA) pain. This meta-analysis is conducted to evaluate short term analgesic effect and safety of duloxetine in the treatment of OA.
Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study. [2022]To assess long-term safety, tolerability, and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis.
Weight change with long-term duloxetine use in chronic painful conditions: an analysis of 16 clinical studies. [2015]Report weight change baseline up to 12-15 months in duloxetine-treated patients during clinical trials of chronic painful conditions of diabetic peripheral neuropathic pain (DPNP), fibromyalgia, chronic low back pain (CLBP) and chronic knee pain as a result of osteoarthritis.
Long-term tolerability and effectiveness of duloxetine in the treatment of major depressive disorder. [2015]To examine the long-term safety, tolerability, and effectiveness of duloxetine in the treatment of major depressive disorder in a naturalistic study design meant to mimic clinical practice. Data were from the long-term, open-label, extension phase that followed a 12-week acute-treatment, multicenter study of adult outpatients with major depressive disorder. After the first week of the acute phase, all patients were treated with at least 60 mg daily duloxetine, which could be titrated to a maximum dose of 120 mg daily. Outcome measures were collected at monthly visits and included spontaneously reported adverse events, weight, vital signs, and the 17-item Hamilton Depression Rating scale. Seventy-two of the 177 (40.7%) patients who entered the extension phase of this study completed the study. The mean duration of participation in the extension was 305 days, with total exposure ranging from 68 to 707 days. Of the 177 patients who entered the extension, only 12 or 13 (7.0%) showed clinically significant worsening of depression that led to study discontinuation. The mean 17-item Hamilton Depression Rating scale score remained below 7 throughout the extension. A total of 21/177 patients (11.9%) discontinued due to adverse events during extension treatment. The adverse events causing discontinuation during the extension, with the exception of weight gain, were generally not unique to the extension phase, with 11/21 patients (52.0%) discontinuing due to adverse events that were first reported during acute treatment. Weight gain was reported as a reason for discontinuation during extension treatment in 4/177 (2.3%) patients. In this open-label study, efficacy was maintained for most patients. The adverse events causing discontinuation during the extension phase were generally not unique to the extension phase. Few patients experienced significant weight gain.
[Exercise therapy in hip or knee osteoarthritis]. [2011]"Exercise is medicine": exercise therapy reduces pain and activity limitations in osteoarthritis of the knee and is likely to have the same effects in osteoarthritis of the hip. Further research into exercise therapy is needed, since disease-modifying drugs are not available, pain medication can cause side effects, and surgical interventions are preferably applied in an advanced stage of disease. Classical exercise therapy is aimed at improving muscle strength, aerobic capacity, range of joint motion, and training of walking and activities of daily living. New modalities of targeted exercise therapy are currently being developed, aimed at the correction of low levels of activity and to correct instability of the knee. Weight loss, preferably combined with exercise therapy, reduces pain and activity limitations in osteoarthritis patients who are overweight. Modalities of exercise therapy adapted to comorbid conditions are currently being developed.
One year effectiveness of neuromuscular exercise compared with instruction in analgesic use on knee function in patients with early knee osteoarthritis: the EXERPHARMA randomized trial. [2018]To test long-term effectiveness of neuromuscular exercise (NEMEX) with instructions in optimized pharmacological treatment (PHARMA) on activities of daily living (ADL) in patients with early knee osteoarthritis.
Exercise Programmes for Osteoarthritis with Different Localization. [2018]Therapeutic exercises in osteoarthritis (OA) are therapeutic approach with proven efficacy. However, the different disease forms, the lack of established consensus and system for patient education limit the widespread use of therapeutic exercises in clinical practice. The mechanisms of action of therapeutic exercise in OA include the following components e.g. neuromuscular (improvement of proprioception, muscle strength and joint stability), intra-articular (prevention of cartilage degeneration, antiinflammatory effect, improvement of the quality of the joint fluid), periarticular, general health with reduction of cardiovascular risk and psychological components. The main exercises, which are used in OA patients, are stretching exercises, range of motion exercises, analytic exercises for muscle strengthening (isometric and isotonic) and aerobic exercises (walking, cycling, swimming, etc.). The recommended exercise programmes have to be individualized according to patient age, severity of OA and presence of concomitant diseases. The analytic exercises for improvement of muscle strength in hip OA aim to influence the abductors, adductors, flexors and extensors of the hip joint. In knee OA, the target muscle groups are thigh muscles (quadriceps muscle and posterior group of thigh muscles), calf muscles (triceps surae muscle) as well as muscles around the hip joint. There are no established programmes for therapeutic exercises regarding the intensity, frequency, the degree and the interval for increasing of joint load. No significant difference in the efficacy of group vs. individual exercise programmes has been observed. In OARSI recommendations (2010), it is underlined that aerobic exercises and those for muscle strength have a moderate efficacy in knee OA for pain relief e.g. ES (effect size) - 0.52 (for aerobic exercises) and 0.32 (for strengthening exercises). The ES for functional improvement is 0.46 for the aerobic exercises and 0.32 for the strengthening exercises. The data for the role of therapeutic exercises in hip OA are scarce. An effect on pain has been observed (ES-0.38) but without improvement of functional capacity. Therapeutic exercises have low to moderate complex efficacy in patients with OA. They should be an obligatory part in the therapeutic regimens of the patients, which requires close collaboration between rheumatologists, general practitioners and physiotherapists as well as establishment of system for patient education.
Managing Hip and Knee Osteoarthritis with Exercise: What is the Best Prescription? [2021]Hip and knee osteoarthritis are common, chronic, and disabling. Therapeutic exercise is a component of all major rheumatologic society guidelines, yet the frequency, dose, duration, and therapeutic threshold for exercise are not clearly delineated. This review summarizes current studies of exercise for hip and knee osteoarthritis, discusses issues that influence the design, interpretation, and aggregation of results and how these factors impact the translation of data into clinical practice. A review of databases to identify current randomized controlled trials (2000 to present) of exercise to manage the symptoms of hip and knee osteoarthritis is discussed here. One study enrolling only hip patients was identified. Six studies of outcomes for individuals with hip or knee osteoarthritis and 11 studies of persons with knee osteoarthritis were found. Limited studies focus specifically on exercise for persons with hip osteoarthritis. Exercise is provided as a complex intervention combining multiple modes and provided in various settings under a range of conditions. Regardless of the variability in results and inherent biases in trials, exercise appears to reduce pain and improve function for persons with knee osteoarthritis and provide pain relief for persons with hip osteoarthritis. Given the complexity of exercise interventions and the specific issues related to study design, novel approaches to the evaluation of exercise are warranted.
The effectiveness of treadmill and swimming exercise in an animal model of osteoarthritis. [2023]Introduction: Osteoarthritis (OA) is considered an inflammatory and degenerative joint disease, characterized by loss of hyaline joint cartilage and adjacent bone remodeling with the formation of osteophytes, accompanied by various degrees of functional limitation and reduction in the quality of life of individuals. The objective of this work was to investigate the effects of treatment with physical exercise on the treadmill and swimming in an animal model of osteoarthritis. Methods: Forty-eight male Wistar rats were divided (n=12 per group): Sham (S); Osteoarthritis (OA); Osteoarthritis + Treadmill (OA + T); Osteoarthritis + Swimming (OA + S). The mechanical model of OA was induced by median meniscectomy. Thirty days later, the animals started the physical exercise protocols. Both protocols were performed at moderate intensity. Forty-eight hours after the end of the exercise protocols, all animals were anesthetized and euthanized for histological, molecular, and biochemical parameters analysis. Results: Physical exercise performed on a treadmill was more effective in attenuating the action of pro-inflammatory cytokines (IFN-γ, TNF-α, IL1-β, and IL6) and positively regulating anti-inflammatories such as IL4, IL10, and TGF-β in relation to other groups. Discussion: In addition to maintaining a more balanced oxi-reductive environment within the joint, treadmill exercise provided a more satisfactory morphological outcome regarding the number of chondrocytes in the histological evaluation. As an outcome, better results were found in groups submitted to exercise, mostly treadmill exercise.