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| Name | Class |
|---|---|
| Arthritis Research UK Pain Centre | UNKNOWN |
| Nottingham University Hospitals NHS Trust | OTHER |
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Despite evidence that topical non-steroidal anti-inflammatory drugs (NSAIDs) and capsaicin are effective in osteoarthritis (OA), it is still unclear why they work for some people but not others. The investigators are undertaking an individual patient data (IPD) meta-analysis to identify responders according to patient characteristics, however, no studies report the presence of synovial hypertrophy or neuropathic-like pain. These two traits are of interest as they may be used to optimise the treatment effects of the two drugs which work via different mechanisms to reduce pain in OA. The investigators are therefore conducting this pilot n-of-1 trial series.
This pilot n-of-1 trial series will investigate whether a person with OA, who has a different balance between inflammatory and neuropathic pain, shows a preference between these mechanistically different treatments. The trial will also be used to offer recommendations on the use of n-of-1 trial series for individualised (precision) medicine in OA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Topical NSAID and topical capsaicin | Experimental | Within each participant: Topical NSAID (A) or capsaicin (B) are taken for a treatment period of four weeks. This is followed by another four week treatment period with the other treatment. These two treatment periods comprise one treatment cycle. The order of treatments within a treatment cycle is determined randomly (AB or BA). This treatment cycle is repeated so that all participants undergo a maximum of three topical NSAID treatment periods and three topical capsaicin treatment periods (i.e., three treatment cycles). This is reduced to two cycles if they are found to meet the criteria for response at the interim analysis (after cycle two). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Topical NSAID | Drug | Applied four times daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline knee pain on 0-10 numeric rating scale (NRS) | Pain experienced in the most painful knee in the past week will be recorded. The following question will be asked for this purpose: "In the past week, on average, how intense was your knee pain rated on a 0-10 scale, where 0 is 'no pain' and 10 is 'pain as bad as could be'?". The change in pain score between period baseline and period end will be calculated | Baseline and end of each treatment period (i.e., after four weeks of treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| End-of-cycle treatment preference | "Considering only the pain relief experienced in this most recent cycle, which treatment do you feel provided satisfactory pain relief?" | At the end of each treatment cycle (i.e., after 4 weeks of NSAID and 4 weeks of capsaicin). |
| End-of-study overall treatment preference |
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Inclusion Criteria:
Men and non-pregnant women who have had ultrasound and radiographic assessments in the Knee Pain in the Community study
o Premenopausal women will need to be on an acceptable contraceptive method
Aged 40-95 years
Knee pain between 4-8 on the NRS
Knee osteoarthritis - defined as knee pain plus radiographic changes, based on previous questionnaire responses and radiographic findings
Predominantly neuropathic or inflammatory phenotypes based on previous questionnaire responses (not current status)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Weiya Zhang, PhD | University of Nottingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Academic Rheumatology, University of Nottingham | Nottingham | Nottinghamshire | NG5 1PB | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33197270 | Derived | Persson MSM, Stocks J, Sarmanova A, Fernandes G, Walsh DA, Doherty M, Zhang W. Individual responses to topical ibuprofen gel or capsaicin cream for painful knee osteoarthritis: a series of n-of-1 trials. Rheumatology (Oxford). 2021 May 14;60(5):2231-2237. doi: 10.1093/rheumatology/keaa561. |
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Requests for the IPD can be made to the Prof Weiya Zhang. Raw de-identified data may be shared
After publication of the study
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| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010003 | Osteoarthritis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D000894 | Anti-Inflammatory Agents, Non-Steroidal |
| D007052 | Ibuprofen |
| D005782 | Gels |
| D002211 | Capsaicin |
| ID | Term |
|---|---|
| D018712 | Analgesics, Non-Narcotic |
| D000700 | Analgesics |
| D018689 | Sensory System Agents |
| D018373 | Peripheral Nervous System Agents |
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N-of-1 trial series: several within-individual, randomised, multiple cross-over trials aggregated into a series.
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| Topical Capsaicin | Drug | Applied four times daily |
|
|
"Considering all the aspects of the treatment, including its effectiveness and ease of application, which treatment do you prefer?" |
| At study completion - following six treatment periods (24 weeks of treatment, excluding washouts) or 4 treatment periods for responders at the interim analysis (16 weeks of treatment, excluding washouts) |
| Weekly knee pain on 0-10 numeric rating scale (NRS) | Pain experienced in the most painful knee in the past week will be recorded. The following question will be asked for this purpose: "In the past week, on average, how intense was your knee pain rated on a 0-10 scale, where 0 is 'no pain' and 10 is 'pain as bad as could be'?". | At end of week 1, week 2, week 3, and week 4 of each treatment period. |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000893 | Anti-Inflammatory Agents |
| D045506 | Therapeutic Uses |
| D018501 | Antirheumatic Agents |
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D053284 | Polyunsaturated Alkamides |
| D000577 | Amides |
| D000475 | Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D005229 | Fatty Acids, Monounsaturated |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D008055 | Lipids |