Ibuprofen Gel or Capsaicin Cream for my Painful Knee Osteoarthritis?

NCT03146689 | Completed

• 1 other identifier: B 10022017
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoarthritis, Knee

Keywords

osteoarthritis; n-of-1; ibuprofen; capsaicin; NSAID; topical

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (3)

• End-of-cycle treatment preference

  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

  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)

  At end of week 1, week 2, week 3, and week 4 of each treatment period.

Study Arms (1)

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).

Drug: Topical NSAID; Drug: Topical Capsaicin

Interventions

Topical NSAID DRUG

Applied four times daily

Also known as: Ibuprofen 5% gel

Topical NSAID and topical capsaicin

Topical Capsaicin DRUG

Applied four times daily

Also known as: Zacin 0.025% cream

Topical NSAID and topical capsaicin

Eligibility Criteria

• Age: 40 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nottingham: lead
• Arthritis Research UK Pain Centre: collaborator
• Nottingham University Hospitals Charity: collaborator

Study Sites (1)

Academic Rheumatology, University of Nottingham

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33197270 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Anti-Inflammatory Agents, Non-Steroidal; Ibuprofen; Gels; Capsaicin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Polyunsaturated Alkamides; Amides; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Officials

• Weiya Zhang, PhD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: N-of-1 trial series: several within-individual, randomised, multiple cross-over trials aggregated into a series.

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 10, 2017
• Study Start: August 4, 2017
• Primary Completion: October 16, 2018
• Study Completion: October 16, 2018
• Last Updated: April 18, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After publication of the study

Locations

GB (1)