Exercise Plus Duloxetine for Knee Osteoarthritis

NCT04111627 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: HP-00089160K01AG064041
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Knee Osteoarthritis; Depression

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Change from Baseline Depression Severity at 12 weeks

Study Arms (1)

Aerobic exercise plus Duloxetine

EXPERIMENTAL

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

Interventions

Aerobic exercise 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.

Aerobic exercise plus Duloxetine

Duloxetine 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.

Aerobic exercise plus Duloxetine

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• English speaking
• years or older
• Symptomatic knee osteoarthritis fulfilling 1986 American College of Rheumatology criteria
• No plan for surgical knee osteoarthritis intervention within six months of enrollment
• Major depressive disorder satisfying diagnostic criteria according to the DSM-V
• Ability to participate in a supervised aerobic exercise program

You may not qualify if:

• Already performing aerobic or resistive exercise 2x/week or more
• Taking duloxetine, antipsychotics, benzodiazepines, or opioid analgesics
• Other medications deemed by study team to endanger the health of the participant or unduly confound the results
• Cognitive impairment (Mini-Mental State Examination score \< 20)
• Past or current bipolar disorder or psychotic symptoms according to the DSM-V
• Substance abuse disorder or suicidal ideation within the previous year
• 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.
• Active cancer that is currently undergoing treatment (receiving chemotherapy and/or radiation therapy)
• Pregnant or lactating women
• Other conditions deemed by study team to endanger the health of the participant or unduly confound the results

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Related Publications (1)

• 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.

  PMID: 38130375 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Depression

Interventions

Exercise; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: October 1, 2019
• Study Start: October 7, 2021
• Primary Completion: August 11, 2025
• Study Completion: August 11, 2025
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)