A Phase 2 interventional study of Aerobic exercise and Duloxetine in Knee Osteoarthritis and Depression, sponsored by University of Maryland, Baltimore. Completed at 1 site in United States. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2025-10-07.
Sponsored by University of Maryland, Baltimore · Phase 2, Interventional, and Treatment
This study evaluates the addition of duloxetine to aerobic exercise in the treatment of symptomatic knee osteoarthritis and depressive symptoms in adults. All participants will receive the receive the treatment protocol, which will first be evaluated in terms of feasibility and then pilot tested.
Symptomatic knee osteoarthritis (OA) affects 10% of men and 13% of women 60 years or older, and depressive symptoms are common, occurring in one-fifth of these patients. Depressive symptoms worsen knee OA disease severity and are a barrier to pain management and engagement in physical activity. Guidelines recommend depression treatment in older adults with knee OA but provide no direction on how to simultaneously manage the co-occurrence of physical and mental morbidity. Treatment recommendations advise exercise to manage pain and disability and improve psychosocial health in knee OA patients; however, compliance to exercise programs is low in persons with chronic pain and disability and is only made worse by comorbid depression. Adherence is critical to the efficacy of depression treatments using exercise training, and no such exercise program has ever been designed for and tested in OA patients with co-occurring depressive symptoms in a way to enhance compliance. Duloxetine is the only antidepressant medication indicated for pain management in knee OA patients that has demonstrated efficacy and tolerability when treating depression in older adults and is a viable pharmacological complement to exercise. There are no protocols that combine treatments using interventions that affect symptoms of both knee OA and depression, and the study goals are to evaluate the feasibility of and then pilot test a protocol comprised of aerobic exercise training plus duloxetine for the treatment of symptomatic knee OA and comorbid depression.
3,302 studies on the registry are indexed under Osteoarthritis, Knee; 608 are open to participants now.
This study's enrollment of 43 is below the median of 70 across 2,731 interventional studies indexed under Osteoarthritis, Knee.
Browse Osteoarthritis, Knee studies →University of Maryland, Baltimore is the lead sponsor of 687 studies on the registry; 130 are open to participants now.
Of its 90 completed or terminated interventional studies of FDA-regulated products, 63 (70%) have results posted.
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Exclusion Criteria:
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.
Behavioral: Aerobic exercise · Drug: Duloxetine
Participants with symptomatic knee osteoarthritis and depressive symptoms will be enrolled in a progressive walking program designed to reduce pain and disability and improve psychosocial health.
Duloxetine is an FDA-approved selective serotonin and norepinephrine reuptake inhibitor antidepressant approved for the treatment of neuropathic pain in symptomatic knee osteoarthritis as well as depression in adults. Participants with symptomatic knee osteoarthritis and depressive symptoms will receive duloxetine to decrease pain and depression severity to enhance their ability to engage in aerobic exercise.
Knee Osteoarthritis Outcomes Scale (KOOS) pain subscale
The self-reported KOOS pain subscale is sensitive to changes in knee OA symptoms, and consists of nine items scored on a Likert scale (0 \[No problems\] to 4 \[Extreme Problems\]) that ranges from 0-36, with higher values indicating greater severity.
Time frame: Change from Baseline Pain Severity at 12 weeks
Hamilton Depression Rating Scale (HAM-D)
The HAM-D is clinician-administered, 21-item questionnaire, designed to rate the severity of depression in patients. Individual scores are based on the first 17 items, each with a possible score of 0-4 (0=Absent; 4=Extreme Symptoms) or 0-2 (0=Absent; 2=Frequent), yielding an overall range of 0-54. Higher scores indicate greater depression severity.
Time frame: Change from Baseline Depression Severity at 12 weeks
Plan to share: No
This study is completed, as verified in Oct 2025. You cannot join it, but the record below documents what was studied.
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University of Maryland, Baltimore