Probing the Rheumatoid Arthritis Brain to Elucidate Central Pain Pathways

NCT05693532 | Completed

• 1 other identifier: GN19RH007
• Study Type: observational
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis (RA) is a common disease which is characterised by severe joint inflammation and chronic pain. The discovery of new joint specific treatments has transformed patient outcomes and yet most patients, even those whose joints respond fully to these treatments, continue to experience significant levels of pain. The investigators therefore believe that RA pain is caused by alternative sources in addition to the joints. Our group are pioneering the investigation of a possible link between the brain and the pain which RA patients experience. By employing sophisticated brain scanning methods, the investigators have shown that high levels of pain and blood inflammation are associated with changes within a specific region of the brain known as the left inferior parietal lobule(L-IPL). This region exhibited abnormal connections with other brain regions already known to be associated with pain in another chronic pain disorder called fibromyalgia. Fibromyalgia is a musculoskeletal condition which is not classically related to high levels of blood inflammation, although, interestingly, it is not uncommon for it to co-exist in RA patients. In light of our preliminary brain scan studies, the investigators now think that fibromyalgia in the context of RA may be partially influenced by inflammation. In order to fully understand the precise processes that lead to this potential relationship, it is important to characterise the biological abnormalities that underlie our brain scan observations. Previous animal experiments have consistently observed abnormalities, such as high levels of the brain chemical glutamate and haphazard brain activity, in the context of inflammation. Conducting similar experiments in humans is not practical due to the inherent dangers of sampling live brain tissue. Instead, neuroscientists commonly use non-invasive methods to manipulate specific parts of the brain in order to better understand how they function. In conjunction, the latest scanners are now able to indirectly measure the effect of the brain modulation on relevant aspects of brain biology without the need to remove tissue. This information will help us to better understand the relationship between inflammation and pain in the RA brain.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Changes in functional connectivity and neuronal signal cohesion

  Changes in functional connectivity and neuronal signal cohesion as measured by 7T MRI. Changes are baseline to post-treatment/sham.

  2 hours

• Changes in glutamate signal

  Changes in glutamate signal in the L-IPL as measured by 7T MRS . Changes are baseline to post-treatment/sham.

  2 hours

Secondary Outcomes (12)

• Changes in pain severity

  2 weeks

• Changes from the Michigan Body Map Regional Pain.

  2 weeks

• Changes in RA disease activity as measured by SDAI.

  2 weeks

• Changes in RA disease activity as measured by CDAI.

  2 weeks

• Changes in putative pain confounders as measured by PROMIS-Fatigue

  2 weeks

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will involve participants aged over 18 years with active inflammatory RA who meet the inclusion criteria below and who have none of the specified exclusion criteria. All will give full informed consent. Rheumatoid arthritis patients attending secondary care clinics in NHS GG\&C and in NHS Lanarkshire will be screened for eligibility. NHS Lanarkshire will act as a participant identification centre (PIC) and all study participants will undertake study procedures at the University of Glasgow and the Queen Elizabeth University Hospital (NHS GG\&C).

You may qualify if:

• Adults ≥ 18 years \< 75 years.
• Physician diagnosis of RA
• ACR definition of chronic widespread pain
• Able and willing to maintain usual/ medication for the 6-week study duration
• CRP \> 6mg/L or ESR \> 20mm/hr
• ≥1 swollen joint
• Right-handed (to reduce neuroimaging heterogeneity)

You may not qualify if:

• Inability to provide written informed consent.
• Severe physical impairment (e.g. blindness, deafness, paraplegia).
• Pregnant, planning pregnancy or breast feeding.
• Severe claustrophobia precluding MRI.
• Contraindications to MRI(e.g. metal implants/ pacemaker).
• Contraindication to TMS (e.g. history of seizures).

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead

Study Sites (1)

Queen Elizabeth University Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood samples will be taken for peripheral immunophenotyping including proteomic and transcriptomic analysis.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Neil Basu, MD, PhD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 23, 2023
• Study Start: November 12, 2021
• Primary Completion: September 4, 2023
• Study Completion: September 4, 2023
• Last Updated: November 1, 2023

Record last verified: 2023-10

Locations

GB (1)