Exercise Plus Duloxetine for Knee Osteoarthritis

NCT ID: NCT04111627

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-07
• Study Completion Date: 2025-08-11

Brief Summary

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.

Detailed Description

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.

Conditions

Knee Osteoarthritis; Depression

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aerobic exercise plus Duloxetine

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.

Group Type: EXPERIMENTAL

Aerobic exercise

Intervention Type: BEHAVIORAL

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

Intervention Type: DRUG

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.

Interventions

Aerobic exercise

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.

Intervention Type: BEHAVIORAL

Duloxetine

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. English speaking

2. 40 years or older

3. Symptomatic knee osteoarthritis fulfilling 1986 American College of Rheumatology criteria

4. No plan for surgical knee osteoarthritis intervention within six months of enrollment

5. Major depressive disorder satisfying diagnostic criteria according to the DSM-V

6. Ability to participate in a supervised aerobic exercise program

Exclusion Criteria

1. Already performing aerobic or resistive exercise 2x/week or more

2. Taking duloxetine, antipsychotics, benzodiazepines, or opioid analgesics

3. Other medications deemed by study team to endanger the health of the participant or unduly confound the results

4. Cognitive impairment (Mini-Mental State Examination score < 20)

5. Past or current bipolar disorder or psychotic symptoms according to the DSM-V

6. Substance abuse disorder or suicidal ideation within the previous year

7. Not able to participate in a supervised exercise program based on the presence of unstable angina, recent MI (within last 3 months), hemiparetic gait, inability to walk at least 1mph on treadmill safely, poorly controlled hypertension (resting blood pressure > 190/110), peripheral arterial disease with current foot or leg ulcers, or cardiac or pulmonary disease with exercise tolerance NYHA class 3 or higher.

8. Active cancer that is currently undergoing treatment (receiving chemotherapy and/or radiation therapy)

9. Pregnant or lactating women

10. Other conditions deemed by study team to endanger the health of the participant or unduly confound the results

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Alan Rathbun

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Maryland School of Medicine

Baltimore, Maryland, United States

Countries

United States

References

Rathbun AM, Mehta R, Ryan AS, Dong Y, Beamer B, Golden J, Gallo JJ, Luborsky M, Shardell MD, Peer JE, Hochberg MC. Duloxetine plus exercise for knee osteoarthritis and depression: A feasibility study. Osteoarthr Cartil Open. 2023 Dec 8;6(1):100426. doi: 10.1016/j.ocarto.2023.100426. eCollection 2024 Mar.

Reference Type: DERIVED

PMID: 38130375 (View on PubMed)

Other Identifiers

K01AG064041

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00089160

Identifier Type: -

Identifier Source: org_study_id