Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA)

This study seeks to measure the psychometric properties of a newly developed Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, and investigate the ability of this questionnaire to measure central mechanisms of pain and also to predict worse pain and fatigue outcomes in people with Rheumatoid Arthritis (RA).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis

Detailed Description

Persistent pain and fatigue are prevalent and disabling symptoms in people with Rheumatoid Arthritis, even in the absence of active inflammation. The investigators believe that these symptoms may be a result of abnormal pain processing by the Central Nervous System (CNS), in a process called central sensitization.

The investigators have developed a short, self-report questionnaire to measure central pain mechanisms in people with RA. It is called Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA), and was adapted from a pre-existing questionnaire called CAP-Knee (which measures central sensitization in people with chronic knee pain).

This study aims to measure the psychometric properties of CAP-RA, and the ability of the questionnaire to predict worse pain in the RA population. Secondary objectives of the study include predicting worse fatigue in people with RA, deriving CAP-RA scoring recommendations, investigating other factors associated with persistent RA pain, the association between central sensitization and pain, and investigating the course of pain and fatigue in RA.

Participants will be recruited from a Rheumatology clinic. At baseline and 12 weeks these participants will undergo quantitative sensory testing (QST, pain tests), ultrasound for synovitis, clinical assessments, laboratory tests for systemic inflammation and, complete a questionnaire booklet, including the CAP-RA questionnaire.

Some participants will complete the CAP-RA questionnaire 1 week after the baseline visit to assess the test-retest reliability of the questionnaire.

In addition, participants will provide weekly pain and fatigue self-report via text message (SMS) for 12 weeks.

• Study Type: Observational
• Enrollment (Actual): 95

Contacts and Locations

• Study Contact: Name: Onosi S Ifesemen; Phone Number: +441153231810; Email: mbxosi@nottingham.ac.uk
• Study Contact Backup: Name: Daniel F McWilliams; Phone Number: +441153231942; Email: dan.mcwilliams@nottingham.ac.uk

Study Locations

• United Kingdom
  • Nottinghamshire
    • Mansfield, Nottinghamshire, United Kingdom
      • Sherwood Forest Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include people with Rheumatoid Arthritis receiving care at the Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Nottinghamshire, UK, who meet the eligibility criteria.

Description

Inclusion Criteria:

• Adult (age≥18y) of any sex and ethnicity.
• Satisfy EULAR criteria for RA.
• Active RA, as defined as DAS28 ≥3.2 at baseline visit

Exclusion Criteria:

• Unable to give informed consent.
• Insufficient understanding of spoken or written English to comply with the requirements of the study protocol
• Unable or unlikely to complete the proposed 12-week study follow up (eg. moving house, terminal diagnosis, current or planned pregnancy).
• Active comorbidity (e.g. uncontrolled diabetes mellitus, cancer, infection) requiring changes in medical treatment at baseline
• Major active psychiatric condition (e.g. major depression)
• Inability to meet the requirements of clinical assessments

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Main study cohort; The main study cohort in this single-arm cohort is 250 adults with rheumatoid arthritis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychometric properties of CAP-RA	A detailed assessment of the psychometric properties of CAP-RA. Higher scores indicate stronger central mechanisms of pain.	Baseline
Psychometric properties of CAP-RA	A detailed assessment of the psychometric properties of CAP-RA. Higher scores indicate stronger central mechanisms of pain	1 week test-retest
Bodily pain	Numerical Rating Scale (0-10) of bodily pain - increasing severity	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Sensory Testing	Validation of CAP-RA as a measure of central sensitization. Lower pressure pain detection thresholds indicate greater sensitivity to painful stimulation. Higher temporal summation indicates dysfunctional pain response. Higher conditioned pain modulation indicates more dysfunctional pain response.	Baseline
Quantitative Sensory Testing	Validation of CAP-RA as a measure of central sensitization. Lower pressure pain detection thresholds indicate greater sensitivity to painful stimulation. Higher temporal summation indicates dysfunctional pain response. Higher conditioned pain modulation indicates more dysfunctional pain response.	12 weeks
Fatigue	Bristol Rheumatoid Arthritis Multidimensional Fatigue Scale (BRAFS). 0-70 scale of increasing fatigue.	12 weeks
Change and trajectory of bodily pain	Responses to mobile phone text messages giving 0-10 pain scores.	12 weeks
Change and trajectory of fatigue	Responses to mobile phone text messages giving 0-10 fatigue scores	12 weeks
Physical activity	International Physical Activity Questionnaire (IPAQ) -short form. Lower scores indicate less physical activity.	12 weeks
Functional status	Health Assessment Questionnaire (HAQ). Range 0-3 with higher scores indicating greater disability.	12 weeks
Neuropathic pain mechanisms	PainDETECT. Higher scores indicating greater neuropathic pain mechanisms.	12 weeks
Mental health	Hospital Anxiety and Depression Scale (HADS) - depression and anxiety. Higher scores indicating worse feelings of anxiety and lower mood.	12 weeks
Central sensitization	Central Sensitisation Inventory 9 (CSI-9). Higher scores indicate greater central sensitisation.	12 weeks
Joint inflammation	Ultrasound assessment showing synovitis	12 weeks
Swollen joints	Swollen joint count (0-28)	12 weeks
Inflammation-Erythrocyte sedimentation rate	Erythrocyte sedimentation rate (mm per hour)	12 weeks
Inflammation-CRP	High sensitivity C-reactive protein	12 weeks

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Pfizer; Versus Arthritis
• Investigators: Principal Investigator: David A Walsh, University of Nottingham

Publications and helpful links

General Publications

• Ifesemen OS, McWilliams DF, Ferguson E, Wakefield R, Akin-Akinyosoye K, Wilson D, Platts D, Ledbury S, Walsh DA. Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): protocol for a prospective observational study. BMC Rheumatol. 2021 Jun 24;5(1):23. doi: 10.1186/s41927-021-00187-2.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): September 30, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: August 6, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Fatigue; Central Sensitization
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 20001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Pre-planned analyses will be performed by the study team. Requests for collaborative analyses of IPD, using non-identifiable data, may be made to the study PI.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No