Recruiting
Phase 4

Duloxetine

Sponsor:

Benedict Alter

Code:

NCT07759336

Conditions

Knee Osteoarthritis (Knee OA)

Chronic Pain

Chronic Knee Pain

Eligibility Criteria

Sex: All

Age: 45 - 70+

Healthy Volunteers: Not accepted

Interventions

Duloxetine

Placebo

Study Details

Brief summary:

The goal of this clinical trial is to examine the effects of duloxetine on walking ability and physical activity in patients with knee osteoarthritis. Researchers will compare duloxetine to a placebo (a look-alike substance that contains no drug) to see if duloxetine works to improve walking ability in patients with knee osteoarthritis. At study visits, participants will complete surveys, perform physical function tasks, undergo non-invasive brain imaging, and undergo sensory testing.

Conditions

Knee Osteoarthritis (Knee OA)

Chronic Pain

Chronic Knee Pain

Study ID

NCT07759336

Start date

Sep 15, 2026

Status verified date

Oct, 2026

Completion date

Mar, 2029

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 45 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Knee pain for greater than 6 months.
  • Moderate-to-severe knee pain (>3/10) due to osteoarthritis, as defined by American College of Rheumatology and EULAR diagnostic criteria (Zhang 2010, Altman 1986) on >50% of days in the past month.
  • KL grade 2-4 (Kellgren and Lawrence 1957) indicating significant degenerative changes on knee X-ray. This will be determined on evaluation of weight-bearing clinical X-rays on review of medical records. In the infrequent situation that the patient does not have an X-ray on review of their medical records, then the patient will obtain weight-bearing knee X-rays as part of the Screening Visit.
  • Age: 45-80 years old
  • Gender: Males and females will be recruited.
  • Language: only English-speaking subjects will be included.

Exclusion Criteria:

  • Inflammatory arthritis (e.g. rheumatoid arthritis).
  • More intense pain due to another chronic pain syndrome (e.g. fibromyalgia, hip osteoarthritis)
  • Significant pain or weakness in the lower extremities due to a neurological condition (e.g. lumbar radiculopathy, paresis due to stroke)
  • New, ongoing acute pain
  • Recent use of duloxetine defined as any use within the last 3 months
  • Current use of antidepressants or tramadol
  • Current routine use of more than 30 mg oral morphine equivalents per day (use of <=30 mg OME does not exclude the participant).
  • New treatment that may help knee osteoarthritis (including medication, exercise, behavioral, or complementary and integrative treatments) started in the last month. Stable use of treatments for greater than 1 month does not exclude the participant.
  • Unwillingness to maintain current knee osteoarthritis treatments for the duration of the study. This means that eligible participants must plan for the following: medications and dietary supplements should not change substantially in frequency or dose; behavioral therapy, exercise therapy, and complementary and integrative therapies should be consistent; and there should be no interventional treatments planned for lower extremity musculoskeletal conditions (e.g. joint steroid injections, knee radiofrequency ablation, knee replacement surgery).
  • Recent knee intra-articular injection of steroid or other agent (greater than 1 month does not exclude the participant)
  • Recent knee radiofrequency ablation (greater than 3 months does not exclude the participant)
  • Recent knee arthroscopic surgery (greater than 3 months does not exclude the participant)
  • History of knee replacement or open knee surgery on the index knee, defined as the more painful knee on average over the last month.
  • Inability to walk or climb stairs without significant assistance (e.g. a one-person assist, use a wheelchair; use of a cane does not exclude the participant).
  • Inability to participate in study procedures (e.g. cognitive impairment limiting ability to understand directions, inability to understand and read English)
  • Uncontrolled or unstable medical disorder preventing participation in study procedures
  • History of brain surgery
  • Tattoos on sensory testing sites
  • Pregnancy
  • History of severe renal impairment defined by GFR < 30 ml/min or, if renal function testing is not available on EMR review, patient-reported history of acute or chronic kidney disease of any severity
  • History of chronic liver disease or cirrhosis
  • History of angle-closure glaucoma

Study Design

Enrollment

85 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Duloxetine, then placebo

In Period A, participants will receive duloxetine. In Period B, participants will receive placebo.

experimental: Placebo, then duloxetine

In Period A, participants will receive placebo. In Period B, participants will receive duloxetine.

Interventions

Duloxetine

Duloxetine is an FDA-approved treatment for osteoarthritis. The drug will be prescribed for subjects with knee osteoarthritis pain to improve pain during mobility. The treatment consists of 30 mg of encapsulated duloxetine by mouth once daily for one week followed by 60 mg of encapsulated duloxetine by mouth once daily for 4 weeks. Then, patients will taper back down to 30 mg of encapsulated duloxetine by mouth once daily for one week.

Placebo

The placebo is a capsule that has been filled with an inactive filler, microcrystalline cellulose (Avicel). It will match in look to the overencapsulated duloxetine capsules but not contain the duloxetine itself. Participants will take 1 week of the placebo pill identical in appearance to encapsulated duloxetine 30 mg followed by 4 weeks of the placebo pill identical in appearance to encapsulated duloxetine 60 mg. Then, patients will take one week of the placebo pill identical in appearance to encapsulated duloxetine 30 mg.

Primary outcome measure

  • Distance walked in the 6-minute walking test [ Time Frame: 6 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks. ]

Central Contacts and Locations

Central contacts

Benedict Alter, MD, PhD

412-677-0575bea51@pitt.edu

Emma Racunas, BS

412-665-8052ecr79@pitt.edu

Locations

University of Pittsburgh - Center for Innovation in Pain Care (Research)

Recruiting

Pittsburgh, Pennsylvania, United States, 15206

Contacts

Benedict Alter, MD, PhD

412-677-0575bea51@pitt.edu

More Information

Sponsor

Benedict Alter

Last update posted

Oct 21, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-22. This information was provided to ClinicalTrials.gov by Benedict Alter on 2026-10-21. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.