Exploiting Leading Edge 7T MRI Brain Imaging to Decipher Olumiant's Mode of Analgesic Action in Rheumatoid Arthritis

NCT05112120 | Completed

• 1 other identifier: GN19RH319
• Study Type: observational
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The revolution in treatments for rheumatoid arthritis (RA) has transformed patient outcomes, but many patients continue to experience life disabling pain. Even those who achieve full disease remission with state-of-the-art treatments report substantially higher levels of pain when compared to the general population. Researchers believe this disconnect is due to the existence of pain sources that are in addition to those present in the joints. In particular, the central nervous system (CNS) may have an important role in determining RA pain. According to a recent study, RA patients who received treatment with Olumiant (a Janus Kinase (JAK) inhibitor that works by interfering with the inflammatory processes that lead to the symptoms of RA) reported better and quicker pain improvements compared to those receiving other types of therapy. However, this could not be explained by levels of peripheral inflammation alone and remains to be fully understood. Investigators think this improvement may be related to the role of the JAK pathway in the brain and that inhibition of this pathway with Olumiant could normalise brain connectivity in respect to pain processing. Advanced brain scanning methods have already helped to identify specific regions of the brain that are thought to be important in pain processing and peripheral inflammation; a) enhanced functional connectivity between the Default Mode Network (DMN) and insula and b) enhanced functional connectivity between the Dorsal Attention Network (DAN) and the left inferior parietal lobule (LIPL). This study aims to elucidate the mechanisms of analgesic action of Olumiant by examining changes in functional connectivity and glutamate levels within the CNS and exploring the relationship between MRI markers, pain, clinical phenotype and peripheral immune markers.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• To evaluate the effects of Olumiant on DMN-Insula connectivity

  To measure brain functional connectivity DMN- insula and DNA- LIPL as measured by 7T MRS

  12 weeks

• To evaluate the effects of Oluminant treatment on insular glutamate levels in RA (neurobiological markers of fibromyalgia).

  To examine changes in the insular glutamate signal as measured by the 7T MRS

  12 weeks

Secondary Outcomes (18)

• Changes in clinical phenotype as measured by the EULAR Disease Activity Score (DAS28)

  12 weeks

• Changes in clinical phenotype as measured by the CDAI

  12 weeks

• Changes in clinical phenotype as measured by the SDAI

  12 weeks

• Changes in sickness behaviour as measured by the 7-Day Symptom Diary (Number Rating Scale)

  12 weeks

• Changes in sickness behaviour as measured by the American College of Rheumatology Fibromyalgia Scale

  12 weeks

Study Arms (1)

Single centre single arm observational cohort

Olumiant (4mg) will be administered in line with standard of care guidance. This is the standard dose in line with license for use in active moderate to severe RA. A dose adjustment from 4mg to 2mg is permitted during the study depending on side-effects

Drug: Olumiant

Interventions

Olumiant DRUG

Olumiant (4mg) will be administered in line with standard of care guidance.

Also known as: Baricitinib

Single centre single arm observational cohort

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

Patients with active RA attending clinics in NHS Greater Glasgow and Clyde who are scheduled to begin Olumiant as part of their standard NHS clinical care will be asked to contribute to this study by their point of care team.

You may qualify if:

• Adults ≥ 18 years \< 75 years.
• Clinical diagnosis of RA
• Selected to start Olumiant by their usual rheumatology clinical team in line with local guidance (previous failure of at least 2 DMARDs and moderate to severe disease active disease)
• 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 or breast feeding.
• Contraindications to MRI (e.g. severe claustrophobia).
• Major confounding neurological disease including Multiple Sclerosis, Stroke, Traumatic Brain Injury, Parkinson's Disease, Alzheimer's Disease
• Previous targeted synthetic (e.g. Oluminant, tofacitinib) DMARD exposure.
• Co-morbid medical conditions that may significantly impair physical functional status
• Medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study (e.g., malignancy, psychosis, suicidal ideation)
• BMI \> 40 or unable to lie comfortably in MRI

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Michigan: collaborator

Study Sites (1)

NHS GG&C

Glasgow, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be obtained to allow analysis of inflmamatory markers considered importnat in Rheumatoid Arthritis.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

baricitinib

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, M.D Ph.D

  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: October 1, 2021
• First Posted: November 8, 2021
• Study Start: July 21, 2021
• Primary Completion: August 3, 2023
• Study Completion: August 3, 2023
• Last Updated: October 31, 2023

Record last verified: 2023-10

Locations

GB (1)