A Phase 4 interventional study of Duloxetine and Placebo in Knee Osteoarthritis (Knee OA), Chronic Pain and Chronic Knee Pain, sponsored by Benedict Alter. Recruiting at 1 site in United States. Open to participants aged 45 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Benedict Alter · Phase 4, Interventional, and Treatment
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.
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.
3,292 studies on the registry are indexed under Osteoarthritis, Knee; 623 are open to participants now.
This study's planned enrollment of 85 is above the median of 68 across 2,714 interventional studies indexed under Osteoarthritis, Knee.
Browse Osteoarthritis, Knee studies →This is the only study on the registry with Benedict Alter as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In Period A, participants will receive duloxetine. In Period B, participants will receive placebo.
Drug: Duloxetine · Drug: Placebo
In Period A, participants will receive placebo. In Period B, participants will receive duloxetine.
Drug: Duloxetine · Drug: Placebo
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
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.
Distance walked in the 6-minute walking test
Distance walked during 6 minute walking task
Time frame: 6 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Quantitative sensory testing
Responses to quantitative sensory tests that assess sensation of painful and non-painful stimuli. The stimuli are calibrated and carefully controlled with safety measures to prevent tissue damage.
Time frame: 2-3 hours per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Performance on Stair Climb Test
The stair climb test will assess how long it takes the participant to step fully up and down a single flight of stairs.
Time frame: 5-10 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Pain during physical function tasks
During standardized physical function tests, including a stair climb test, 4-meter walk test, balance test, and 30-second chair stand test, pain intensity will be reported. Pain intensity for each test is reported on the numeric rating scale (0-10) during this battery of tests.
Time frame: 2-3 hours per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Multidimensional pain assessment
Multidimensional aspects of chronic pain will be measured through written surveys.
Time frame: 1 hour per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Brain imaging
Brain activity will be measured non-invasively using functional near-infrared spectroscopy
Time frame: 2-3 hours per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Biomechanics during physical activity
Aspects of body movement will be measured non-invasively during physical performance tests, including the 6-minute walk test.
Time frame: 2-3 hours per measurement; measured several times from enrollment to last study visit for up to 16 weeks
Semi-structured Clinical Evaluation
An evaluation conducted by a physician or nurse practitioner to assess symptoms and clinical features associated with knee OA
Time frame: 1 hour for the evaluation at the first study visit
Performance on the 30-Second Chair Stand Test
Measurement of how many times participants can stand up from sitting in a chair without using hands/arms in a 30 second period.
Time frame: 5-10 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Performance on 4-Meter Walk Test
Measurement of normal gait speed as participants walk a distance of 4 meters.
Time frame: 5-10 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
Performance on balance tests
Measurement of the time participants can balance in a series of positions.
Time frame: 5-10 minutes per measurement; measured several times from enrollment to last study visit for up to 16 weeks.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Started Sep 2026 (actual). Primary completion is estimated for Dec 2028, 27 months after the start.
Of 88 non-industry phase 4 interventional studies under Osteoarthritis, Knee, half reached primary completion within 19 months of starting (the median), counting those still running; a quarter within 10 and three quarters within 32. This study's planned 27 months is above that.
Counting every sponsor, half of 97 studies reached it within 19 months; a quarter within 10 and three quarters within 36.
Since we started tracking on Sep 25, 2026, the dates moved once, on Oct 21, 2026: start Aug 2026 → Sep 2026, primary completion Aug 2028 → Dec 2028 and completion Aug 2028 → Mar 2029.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Duloxetine