Knee Osteoarthritis (Knee OA)Phase 4PACE-UPNCT07759336
Personalized Analgesia Through Central Nervous System Engagement to Unlock Performance
A Phase 4 study testing Duloxetine in people with Knee Osteoarthritis (Knee OA) and Chronic Pain, run by Benedict Alter at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Knee Osteoarthritis (Knee OA), Chronic Pain, Chronic Knee Pain
- What is being tested?
- Duloxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2026to Mar 2029
- Phase
- Phase 4
- 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 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 22Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pittsburgh - Center for Innovation in Pain Care (Research)
Pittsburgh, Pennsylvania, 15206
Benedict Alter, MD, PhD, 412-677-0575, bea51@pitt.edu
About this study
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.
Read the detailed description
Using a double-blind, cross-over, 16-week randomized clinical trial of duloxetine versus placebo, this study will investigate whether duloxetine improves walking ability and physical activity in knee osteoarthritis patients (N=85). Aerobic exercise such as walking is important in preventing joint deterioration and is a first-line treatment for knee osteoarthritis, despite being painful. Indeed, many patients are limited in their ability to walk due to pain. Prior literature and preliminary data from our group indicate that central nervous system (CNS) pain processing contributes to pain-related walking impairment. While acetaminophen, nonsteroidal anti-inflammatories, opioids, and surgery are often used in knee osteoarthritis, side effects and health risks limit their use in many patient subgroups. In patients with CNS changes, these treatments may be less effective. In patients with nociplastic pain related to CNS sensitization, knee replacement is associated with worse post-operative pain and functional outcomes. Potentially targeting CNS sensitization, duloxetine is the only CNS-acting medication FDA-approved for knee osteoarthritis pain, and given that patient-reported physical function improves with duloxetine, its use may slow joint degeneration and delay the need for knee replacement by improving walking ability. However, no clinical trials have investigated whether duloxetine improves objectively measured physical function. This study will address this gap and lead to future large-scale studies examining knee osteoarthritis endophenotypes, related to CNS pain processing and other pathophysiology, which may aid in identifying patients who respond better to duloxetine versus other existing therapies. Techniques used in the setting of this randomized clinical trial include patient-reported outcomes, physical performance tests, actigraphy, noninvasive brain imaging, and quantitative sensory testing.
- Being tested
- Duloxetine, Placebo
- Medical subject headings
- Osteoarthritis, Knee, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuloxetineDrug
Also called Cymbalta
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Duloxetine, then placebo | Experimental | In Period A, participants will receive duloxetine. In Period B, participants will receive placebo. Receives: Drug: Duloxetine; Drug: Placebo |
| Placebo, then duloxetine | Experimental | In Period A, participants will receive placebo. In Period B, participants will receive duloxetine. Receives: Drug: Duloxetine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Distance walked in the 6-minute walking test
Distance walked during 6 minute walking task
Measured: 6 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2026
- Study start15 Sep 2026
- Primary completionDec 2028 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee Osteoarthritis (Knee OA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Benedict Alter
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Benedict Alter, University of Pittsburgh
- Investigators
- Benedict Alter, MD, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07759336
- Sponsor's protocol ID
- STUDY25040070
- Other IDs
- 5K23NS123429
- Acronym
- PACE-UP
- Status last verified
- Oct 2026
- First submitted
- 24 Jul 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalized Analgesia Through Central Nervous System Engagement to Unlock Performance
- ClinicalTrials.gov ID
- NCT07759336
- Acronym / sponsor ID
- PACE-UP / STUDY25040070
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Benedict AlterUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 15 Sep 2026 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 12 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Using a double-blind, cross-over, 16-week randomized clinical trial of duloxetine versus placebo, this study will investigate whether duloxetine improves walking ability and physical activity in knee osteoarthritis patients (N=85). Aerobic exercise such as walking is important in preventing joint deterioration and is a first-line treatment for knee osteoarthritis, despite being painful. Indeed, many patients are limited in their ability to walk due to pain. Prior literature and preliminary data from our group indicate that central nervous system (CNS) pain processing contributes to pain-related walking impairment. While acetaminophen, nonsteroidal anti-inflammatories, opioids, and surgery are often used in knee osteoarthritis, side effects and health risks limit their use in many patient subgroups. In patients with CNS changes, these treatments may be less effective. In patients with nociplastic pain related to CNS sensitization, knee replacement is associated with worse post-operative pain and functional outcomes. Potentially targeting CNS sensitization, duloxetine is the only CNS-acting medication FDA-approved for knee osteoarthritis pain, and given that patient-reported physical function improves with duloxetine, its use may slow joint degeneration and delay the need for knee replacement by improving walking ability. However, no clinical trials have investigated whether duloxetine improves objectively measured physical function. This study will address this gap and lead to future large-scale studies examining knee osteoarthritis endophenotypes, related to CNS pain processing and other pathophysiology, which may aid in identifying patients who respond better to duloxetine versus other existing therapies. Techniques used in the setting of this randomized clinical trial include patient-reported outcomes, physical performance tests, actigraphy, noninvasive brain imaging, and quantitative sensory testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Duloxetine, then placebo | Experimental | Drug: Duloxetine, Drug: PlaceboIn Period A, participants will receive duloxetine. In Period B, participants will receive placebo. |
| Placebo, then duloxetine | Experimental | Drug: Duloxetine, Drug: PlaceboIn Period A, participants will receive placebo. In Period B, participants will receive duloxetine. |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DuloxetineAlso: CymbaltaDuloxetine 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. | Drug | Duloxetine, then placebo, Placebo, then duloxetine |
| PlaceboThe 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. | Drug | Duloxetine, then placebo, Placebo, then duloxetine |
Primary outcome
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.
Distance walked during 6 minute walking task
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Benedict Alter, MD, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Duloxetine in people with Knee Osteoarthritis (Knee OA) and Chronic Pain, run by Benedict Alter 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 22 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: looking for participants now, as of the sponsor's last update on 21 Oct 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Benedict Alter, MD, PhD (412-677-0575, bea51@pitt.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Oct 2026.