Duloxetine and aeRobic Exercise to Improve Function in VEterans With Knee Osteoarthritis (DRIVE)

NCT07649291 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: RRD2-005-25W1 I01 RD002117
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

Knee osteoarthritis (KOA) is one of the most common causes of chronic pain, mobility problems, and disability among United States Veterans. Many Veterans with KOA also experience depressive symptoms, which can worsen pain, reduce motivation to exercise, and make recovery more difficult. This study will test whether a structured hybrid aerobic exercise program that combines supervised and home-based walking with the medication duloxetine can improve physical function, reduce pain, lessen depressive symptoms, and improve overall health-related outcomes in Veterans with KOA. The goal of this research is to develop a practical and scalable treatment strategy that could improve rehabilitation and quality of life for Veterans with chronic knee pain and depressive symptoms and potentially be adapted for other chronic musculoskeletal conditions treated within the VA healthcare system.

Conditions

Knee Osteoarthritis; Pain; Depression

Keywords

Exercise; Pain; Depressive symptoms; Physical Function; Duloxetine

Outcome Measures

Primary Outcomes (1)

• 20-Meter Walk Test

  20m WT (average time to walk 20 meters at usual pace across two trials) from baseline to 12 weeks, and between-group comparison (aerobic exercise + duloxetine vs. PT referral + duloxetine)

  baseline, 12-week follow-up

Secondary Outcomes (2)

• Pain severity

  baseline, 12-week follow-up

• Depressive symptoms

  baseline, 12-week follow-up

Study Arms (3)

Exercise+Duloxetine

ACTIVE COMPARATOR

hybrid supervised aerobic exercise plus duloxetine

Behavioral: Exercise; Drug: Duloxetine

Duloxetine+PT referral

ACTIVE COMPARATOR

duloxetine plus physical therapy (PT) referral

Drug: Duloxetine; Behavioral: PT referral

Exercise+Placebo

ACTIVE COMPARATOR

hybrid supervised aerobic exercise plus placebo

Behavioral: Exercise; Drug: Placebo

Interventions

Exercise BEHAVIORAL

Participants will be asked to participate in a 1x/week center-based exercise session and 2x/week walking session conducted on their own for \~12 weeks.

Exercise+Duloxetine; Exercise+Placebo

Duloxetine DRUG

Participants will receive study medication - duloxetine - and take medication as directed.

Duloxetine+PT referral; Exercise+Duloxetine

Placebo DRUG

Participants will receive study medication - matched placebo- and take as directed.

Exercise+Placebo

PT referral BEHAVIORAL

Participants will be referred to physical therapy with treatment as part of usual care and individualized to the Veteran's needs.

Duloxetine+PT referral

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veterans aged ≥40 years
• English-speaking
• symptomatic KOA based on American College of Rheumatology (ACR) criteria
• Patient Health Questionnaire-9 (PHQ-9) scores indicating mild to severe depressive symptoms
• no planned knee surgery within the next 6 months
• ability to participate in supervised aerobic exercise

You may not qualify if:

• current use of antidepressants, opioids, benzodiazepines, or antipsychotics
• engaging in structured aerobic or resistance exercise ≥3 times per week
• cognitive impairment defined as a Mini-Mental State Examination (MMSE) score \<20
• diagnosis of bipolar disorder, psychosis, recent substance use disorder, or suicidal ideation per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• medical conditions contraindicating exercise (e.g., recent myocardial infarction, unstable angina, peripheral arterial disease with ulcers, -uncontrolled hypertension \>190/110, or New York Heart Association class ≥3 cardiac or pulmonary disease)
• pregnant or lactating individuals
• active cancer that is currently undergoing treatment (receiving chemotherapy and/or radiation therapy
• other conditions deemed by study team to endanger the health of the participant

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Baltimore VA Medical Center: collaborator

Study Sites (1)

Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain; Depression; Motor Activity

Interventions

Exercise; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; 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 Officials

• Alan M Rathbun, PhD MPH

  Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

  PRINCIPAL INVESTIGATOR

• Alice S. Ryan, PhD

  Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alice S Ryan, PhD

CONTACT

(410) 605-7851; Alice.Ryan@va.gov

Kristina Marcus, MS

CONTACT

(410) 605-7000; kristina.marcus@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants randomized to receive the exercise program will be blinded to duloxetine or placebo. Outcome assessors will be blinded to treatment allocation/group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: * (1) hybrid supervised aerobic exercise plus duloxetine * (2) duloxetine plus physical therapy (PT) referral representing a usual care comparator condition, or * (3) hybrid supervised aerobic exercise plus placebo

Study Record Dates

• First Submitted: June 10, 2026
• First Posted: June 16, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2032
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)