Clinical trial NCT03146689: Ibuprofen Gel or Capsaicin Cream for my Painful Knee Osteoarthritis?
Official title: Identifying Treatment Responders to a Topical Non-steroidal Anti-inflammatory Drug (NSAID) or Topical Capsaicin in Painful Knee Osteoarthritis: A Pilot Series of N-of-1 Trials
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis, Knee
Keywords: osteoarthritis
n-of-1
ibuprofen
capsaicin
NSAID
topical
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: Arthritis Research UK Pain Centre
name: Nottingham University Hospitals Charity
First posted: 2017-05-10
Enrollment: 22
Sex: ALL
Minimum age (years): 40
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: N-of-1 trial series: several within-individual, randomised, multiple cross-over trials aggregated into a series.
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

  * Knee pain: individuals with knee pain in and around the knee on most days for at least a month.
  * Radiographic changes: definite joint space narrowing and definite osteophytes (each scoring two or more on the Nottingham Line Drawing Atlas) in the tibiofemoral and/or patellofemoral compartments
* Predominantly neuropathic or inflammatory phenotypes based on previous questionnaire responses (not current status)

  * Predominantly neuropathic phenotype: painDETECT Questionnaire (PDQ) \> 13 and synovial hypertrophy (SH) \<4 mm
  * Predominantly inflammatory phenotype: SH \> 4 mm and PDQ \< 13
  * If we cannot recruit enough people with the above thresholds, we will base recruitment on the overall distribution of PDQ and SH scores from the population. The third tertile of PDQ and the first tertile of SH for neuropathic and the first tertile of PDQ and the third tertile of SH for inflammatory phenotypes.

Exclusion Criteria:

* Inability to give informed consent
* Daily use of oral NSAIDs for the last two weeks
* Prior use of Ibuprofen gel or Zacin on the affected knee(s)
* Terminal or untreated major mental illness
* Pregnancy or breastfeeding
* Hypersensitivity or allergy to topical NSAIDs, capsaicin, or other ingredients in the preparations. This includes individuals that experience attacks of asthma, urticaria, or acute rhinitis that are precipitated by NSAIDs
* Current treatment for stomach or duodenal ulcers
* Total joint replacement of affected joint
* Renal failure
* Taking anticoagulants

Primary outcomes:
measure: Change from baseline knee pain on 0-10 numeric rating scale (NRS)
timeFrame: Baseline and end of each treatment period (i.e., after four weeks of treatment)
Secondary outcomes:
measure: End-of-cycle treatment preference
timeFrame: At the end of each treatment cycle (i.e., after 4 weeks of NSAID and 4 weeks of capsaicin).
measure: End-of-study overall treatment preference
timeFrame: 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)
measure: Weekly knee pain on 0-10 numeric rating scale (NRS)
timeFrame: At end of week 1, week 2, week 3, and week 4 of each treatment period.
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Academic Rheumatology, University of Nottingham
state: Nottinghamshire
Study officials:
affiliation: University of Nottingham
name: Weiya Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.