7 Tesla MRI Brain Imaging to Decipher Filgotinib's Mode of Analgesic Action in Rheumatoid Arthritis

NCT05697159 | Recruiting

• 1 other identifier: GN22RH315
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an experimental medicine, single-centre, observational test-retest study to evaluate Filgotinib's mechanism of analgesic action in RA patients. The investigators hypothesize that Filgotinib's mechanism of analgesic action is determined by at least two factors. The first is related to those CNS sensitization pathways seen in fibromyalgia, specifically DMN-insula brain functional connectivity and insular glutamate. The second is related to peripheral inflammation, specifically joint synovitis, blood cytokines/chemokines and DAN-LIPL functional brain connectivity. The CNS sensitization pain pathways related to fibromyalgia are more quickly modified compared to those related to peripheral inflammation and help explain Filgotinib's rapid onset of effect.

Conditions

Rheumatoid Arthritis; Sickness Behavior; Inflammatory Disease; Autoimmune; Pain, Chronic

Keywords

Chronic pain; Rhuematoid arthritis

Outcome Measures

Primary Outcomes (2)

• To evaluate the effects of Filgotinib in RA on CNS pain sensitisation (as measured by MRI brain) for DMN-Insula fMRI brain connectivity at 12 weeks.

  Functional connectivity MRI (fMRI) investigations are conducted with subjects resting in the scanner. Ten minutes of whole-brain resting state fMRI data will be collected using a simultaneous-multi-slice (SMS) echoplanar-imaging (EPI) sequence of factor=3. A whole-brain T1-weighted structural image will also be collected using a twice magnetization-prepared rapid gradient echo (MP2RAGE) sequence. During the resting state, subjects will be instructed not to undertake any particular task and to stay awake with their eyes open on a fixation cross. Whole brain coverage will be performed. Upon collection of resting state fMRI data, pre-processing steps will include the removal of physiological artefacts, motion correction, realignment, registration, normalization and smoothing. Connectivity indices will be generated from matrices informed by our a priori determined regions of interest (DMN-Insula).

  12 weeks

• To evaluate the effects of Filgotinib in RA on CNS pain sensitisation (as measured by MRI brain) for insular glutamate levels at 12 weeks.

  A magnetic resonance spectroscopy scan will be undertaken in order to detect the glutamate concentration. A single voxel sequence will be employed with semi-LASER preparation. A 20x20 mm3 voxel will be placed in the R posterior insula and shimming oA magnetic resonance spectroscopy scan will be undertaken in order to detect the glutamate concentration. A single voxel sequence will be employed with semi-LASER preparation. A 20x20 mm3 voxel will be placed in the R posterior insula and shimming of the static magnetic field will be performed using advanced methods best suited to MRS acquisition at 7T, such as FASTMAP. Spectra will be analysed and quantified in JMRUI or LCModel. In addition, multi-voxel techniques will be employed to provide quantitative maps of chemical concentration across the brain.

  12 weeks

Secondary Outcomes (30)

• To evaluate the effects of Filgotinib in RA on CNS pain sensitisation (as measured by MRI brain) for DMN-Insula fMRI brain connectivity at 4 weeks.

  0-4 weeks

• To evaluate the effects of Filgotinib in RA on CNS pain sensitisation (as measured by MRI brain) for insular glutamate levels at 4 weeks.

  0-4 weeks

• To evaluate the effects of Filgotinib in RA on peripheral inflammation related pain as measured by MRI brain for DAN-LIPL fMRI brain connectivity (neurobiological marker of peripheral inflammatory pain) in the short term.

  0-4 weeks

• To evaluate the effects of Filgotinib in RA on peripheral inflammation related pain as measured by MRI brain for DAN-LIPL fMRI brain connectivity (neurobiological marker of peripheral inflammatory pain) in the medium term.

  12 weeks

• To evaluate the effects of Filgotinib in RA on peripheral inflammation related pain as measured by ultrasound joint, in the short term.

  0-4 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 20 participants aged over 18 years with moderate to severe active RA, who have failed at least methotrexate, who fulfil the eligibility criteria below and who are scheduled to start Filgotinib as part of standard clinical practice. All will give full informed consent. The decision to commence filgotinib treatment, completion of all standard pre-biologic safety screening requirements, contraception requirements and patient consent to filgotinib treatment will be undertaken by the participant's usual care team as part of standard clinical practice and will be separate, and in advance of participation in this study.

You may qualify if:

• Patients with moderate to severe active RA who have been prescribed filgotinib in line with the Summary of Product Characterisation and are:
• Adults ≥18 years \< 75 years.
• 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.
• Severe claustrophobia precluding MRI.
• Contraindications to MRI.
• Major confounding neurological disease including MS, Stroke, Traumatic Brain Injury.
• Previous targeted synthetic (e.g. baricitinib, tofacitinib) DMARD exposure for RA.

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• Galapagos NV: collaborator

Study Sites (1)

Neil Basu

Glasgow, United Kingdom

RECRUITING

Related Publications (3)

• Basu N, Kaplan CM, Ichesco E, Larkin T, Harris RE, Murray A, Waiter G, Clauw DJ. Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients. Arthritis Rheumatol. 2018 Jul;70(7):1000-1007. doi: 10.1002/art.40451. Epub 2018 May 11.

  PMID: 29439291 BACKGROUND

• D'Agostino MA, Terslev L, Aegerter P, Backhaus M, Balint P, Bruyn GA, Filippucci E, Grassi W, Iagnocco A, Jousse-Joulin S, Kane D, Naredo E, Schmidt W, Szkudlarek M, Conaghan PG, Wakefield RJ. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 1: definition and development of a standardised, consensus-based scoring system. RMD Open. 2017 Jul 11;3(1):e000428. doi: 10.1136/rmdopen-2016-000428. eCollection 2017.

  PMID: 28948983 BACKGROUND

• Schrepf A, Kaplan CM, Ichesco E, Larkin T, Harte SE, Harris RE, Murray AD, Waiter GD, Clauw DJ, Basu N. A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis. Nat Commun. 2018 Jun 8;9(1):2243. doi: 10.1038/s41467-018-04648-0.

  PMID: 29884867 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Research blood samples will be collected for peripheral immune phenotyping.

MeSH Terms

Conditions

Arthritis, Rheumatoid; Illness Behavior; Chronic Pain

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Behavior; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Neil Basu, MD, PhD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maxine Arnott

CONTACT

0141 330 8388; maxine.arnott@glasgow.ac.uk

Neil Basu, MD, PhD

CONTACT

0141 330 1718; neil.basu@glasgow.ac.uk

Study Design

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

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: January 25, 2023
• Study Start: August 22, 2023
• Primary Completion: July 31, 2025
• Study Completion: October 31, 2025
• Last Updated: January 14, 2025

Record last verified: 2025-01

Locations

GB (1)