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Knee OsteoarthritisPhase 2DRIVENCT07649291

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

A Phase 2 study testing Exercise, Duloxetine and PT referral in people with Knee Osteoarthritis and Pain, run by VA Office of Research and Development at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 years and olderHealthy volunteers can take part
Conditions the study is for
Knee Osteoarthritis, Pain, Depression
What is being tested?
Exercise, Duloxetine and PT referral
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
102 participants
Where
1 siteUnited States
Study dates
1 Mar 2027to 1 Sep 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Alice S Ryan, PhD contact

(410) 605-7851

Alice.Ryan@va.gov

Kristina Marcus, MS contact

(410) 605-7000

kristina.marcus@va.gov

United States1 site

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

    Baltimore, Maryland, 21201

    Alice S Ryan, PhD, 410-605-7851, Alice.Ryan@va.gov

    Alan M Rathbun, PhD MPH

Other trials in United States

About this study

Official title: Duloxetine Plus Exercise to Improve Physical Function in Veterans With Knee Osteoarthritis, Pain, and Psychological Comorbidity

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.

Read the detailed description

Knee osteoarthritis (KOA) and depressive symptoms are both common among older adults and Veterans and are major contributors to chronic pain, reduced mobility, declines in physical function, disability, and poorer overall health outcomes. Veterans with KOA frequently experience co-occurring depressive symptoms, which can worsen pain, interfere with rehabilitation, and reduce adherence to exercise and other self-management strategies. Existing VA care guidelines generally treat KOA and depressive symptoms separately, and there remains limited evidence supporting integrated interventions that target both conditions simultaneously while also improving physical function.

Current knowledge gaps include how to optimize adherence to aerobic exercise among individuals with pain and depressive symptoms and whether combining pharmacologic and rehabilitative approaches provides greater benefit than usual care alone. Aerobic exercise is a recommended first-line treatment for KOA and can improve both mood and physical function, but sustained participation is often difficult in individuals with chronic pain and depressive symptoms. Similarly, duloxetine has demonstrated benefits for both depressive symptoms and KOA-related pain, although interventions targeting only one condition have generally produced limited effects.

Preliminary work conducted by the study team demonstrated that combining duloxetine with a hybrid supervised aerobic exercise program that included both center-based and home-based walking components was feasible and acceptable among individuals with symptomatic KOA and depressive symptoms. Participants experienced clinically meaningful improvements in pain, activities of daily living, walking ability, endurance, psychological symptoms, self-efficacy, and willingness to engage in pain self-management strategies. These findings support the rationale for the proposed study and the evaluation of a complementary care model integrating pharmacologic and non-pharmacologic treatments for Veterans with KOA and depressive symptoms. This study is a Phase II, three-arm, randomized clinical trial designed to evaluate the efficacy of a hybrid supervised aerobic exercise program combined with duloxetine among Veterans with symptomatic knee osteoarthritis and depressive symptoms.

Being tested
Exercise, Duloxetine, Placebo, PT referral
Keywords
Exercise, Pain, Depressive symptoms, Physical Function, Duloxetine
Medical subject headings
Osteoarthritis, Knee, Pain, Depression, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ExerciseBehavioural

    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.

  • DuloxetineDrug

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

  • PlaceboDrug

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

  • PT referralBehavioural

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

Study groups in NCT07649291
Study groupRoleWhat they receive
Exercise+DuloxetineActive comparatorhybrid supervised aerobic exercise plus duloxetine
Receives: Behavioral: Exercise; Drug: Duloxetine
Duloxetine+PT referralActive comparatorduloxetine plus physical therapy (PT) referral
Receives: Drug: Duloxetine; Behavioral: PT referral
Exercise+PlaceboActive comparatorhybrid supervised aerobic exercise plus placebo
Receives: Behavioral: Exercise; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: baseline, 12-week follow-up

Secondary outcomes (2)

  1. Pain severity

    The Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale is a patient-reported measure of knee pain consisting of 9 items. Scores are transformed to a 0-100 scale, where 0 represents extreme knee pain and 100 represents no knee pain. Higher scores indicate better outcomes (less pain).

    KOOS Pain is a self-report measure with five subscales. The pain subscale will be the pain outcome.

    Measured: baseline, 12-week follow-up

  2. Depressive symptoms

    The Hamilton Depression Rating Scale (HAM-D) is a clinician-administered measure of depressive symptom severity. Total scores range from 0 to 52, with higher scores indicating more severe depressive symptoms and worse outcomes. Lower scores indicate improvement in depressive symptoms.

    Hamilton Depression Rating Scale (HAM-D) is a 17-item interviewer-administered scale.

    Measured: baseline, 12-week follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2026
  2. Study start1 Mar 2027 (estimated)
  3. Primary completion1 Sep 2031 (estimated)
  4. Study completion1 Sep 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
* (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
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
102 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07649291
Sponsor's protocol ID
RRD2-005-25W
Other IDs
1 I01 RD002117
Acronym
DRIVE
Status last verified
Jun 2026
First submitted
10 Jun 2026
Last updated
16 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Exercise, Duloxetine and PT referral in people with Knee Osteoarthritis and Pain, run by VA Office of Research and Development at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Alice S Ryan, PhD ((410) 605-7851, Alice.Ryan@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

20-Meter Walk Test (time frame: baseline, 12-week follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07649291.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.

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