Personalized Analgesia Through Central Nervous System Engagement to Unlock Performance

NCT07759336 | Not Yet Recruiting Phase 4 FDA Drug

• 2 other identifiers: STUDY250400705K23NS123429
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Distance walked in the 6-minute walking test

  Distance walked during 6 minute walking task

  6 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.

Other Outcomes (10)

• Quantitative sensory testing

  2-3 hours per measurement; measured several times from enrollment to last study visit for up to 16 weeks.

• Performance on Stair Climb Test

  5-10 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.

• Pain during physical function tasks

  2-3 hours per measurement; measured several times from enrollment to last study visit for up to 16 weeks.

Study Arms (2)

Duloxetine, then placebo

EXPERIMENTAL

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

Drug: Duloxetine; Drug: Placebo

Placebo, then duloxetine

EXPERIMENTAL

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

Drug: Duloxetine; Drug: Placebo

Interventions

Duloxetine DRUG

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.

Also known as: Cymbalta

Duloxetine, then placebo; Placebo, then duloxetine

Placebo DRUG

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.

Duloxetine, then placebo; Placebo, then duloxetine

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Benedict Alter: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

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

Pittsburgh, Pennsylvania, 15206, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Chronic Pain

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Benedict Alter, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benedict Alter, MD, PhD

CONTACT

412-677-0575; bea51@pitt.edu

Emma Racunas, BS

CONTACT

412-665-8052; ecr79@pitt.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: August 12, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: August 12, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)