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Ibuprofen Gel or Capsaicin Cream for my Painful Knee Osteoarthritis?

Primary Purpose

Osteoarthritis, Knee

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Topical NSAID
Topical Capsaicin
Sponsored by
University of Nottingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Osteoarthritis, Knee focused on measuring osteoarthritis, n-of-1, ibuprofen, capsaicin, NSAID, topical

Eligibility Criteria

40 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Academic Rheumatology, University of Nottingham

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Topical NSAID and topical capsaicin

Arm Description

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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?"
End-of-study overall treatment preference
"Considering all the aspects of the treatment, including its effectiveness and ease of application, which treatment do you prefer?"
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'?".

Full Information

First Posted
May 3, 2017
Last Updated
April 16, 2019
Sponsor
University of Nottingham
Collaborators
Arthritis Research UK Pain Centre, Nottingham University Hospitals Charity
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1. Study Identification

Unique Protocol Identification Number
NCT03146689
Brief Title
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

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
August 4, 2017 (Actual)
Primary Completion Date
October 16, 2018 (Actual)
Study Completion Date
October 16, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nottingham
Collaborators
Arthritis Research UK Pain Centre, Nottingham University Hospitals Charity

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
osteoarthritis, n-of-1, ibuprofen, capsaicin, NSAID, topical

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
N-of-1 trial series: several within-individual, randomised, multiple cross-over trials aggregated into a series.
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Topical NSAID and topical capsaicin
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Topical NSAID
Other Intervention Name(s)
Ibuprofen 5% gel
Intervention Description
Applied four times daily
Intervention Type
Drug
Intervention Name(s)
Topical Capsaicin
Other Intervention Name(s)
Zacin 0.025% cream
Intervention Description
Applied four times daily
Primary Outcome Measure Information:
Title
Change from baseline knee pain on 0-10 numeric rating scale (NRS)
Description
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
Time Frame
Baseline and end of each treatment period (i.e., after four weeks of treatment)
Secondary Outcome Measure Information:
Title
End-of-cycle treatment preference
Description
"Considering only the pain relief experienced in this most recent cycle, which treatment do you feel provided satisfactory pain relief?"
Time Frame
At the end of each treatment cycle (i.e., after 4 weeks of NSAID and 4 weeks of capsaicin).
Title
End-of-study overall treatment preference
Description
"Considering all the aspects of the treatment, including its effectiveness and ease of application, which treatment do you prefer?"
Time Frame
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)
Title
Weekly knee pain on 0-10 numeric rating scale (NRS)
Description
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'?".
Time Frame
At end of week 1, week 2, week 3, and week 4 of each treatment period.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weiya Zhang, PhD
Organizational Affiliation
University of Nottingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academic Rheumatology, University of Nottingham
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG5 1PB
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Requests for the IPD can be made to the Prof Weiya Zhang. Raw de-identified data may be shared
IPD Sharing Time Frame
After publication of the study
Citations:
PubMed Identifier
33197270
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.
Results Reference
derived

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