NCT05090124

Experimental Medicine Studies of the Brain in Patients With Rheumatoid Arthritis REALISE

Experimental Medicine Studies of Brain and Peripheral Immune Mechanisms for Sickness Behaviours in Patients With Rheumatoid Arthritis

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: NHS Greater Glasgow and Clyde · Academic / Other
• Sex: All
• Age: 18 Years – 74 Years
• Healthy volunteers: Not accepted

Summary

The rationale for this study is to use immune molecule-specific drug treatment to leverage a mechanistic understanding of the brain changes that drive sickness behaviour. This will combine current therapy with innovative neuroimaging technologies to obtain data in humans that has hitherto only been available in animal studies. Data supporting the role of inflammatory molecules in sickness behaviours and other cognitive disorders are increasingly compelling. A putative mechanism linking inflammatory proteins to sickness behaviour is Tumour Necrosis Factor (TNF)-driven increases in extracellular glutamate leading to changes in neural function and brain network integrity and ultimately to sickness behaviour. Investigators hypothesise that TNF antagonism will effect changes in brain network connectivity and sickness behaviour score, that Rheumatoid Arthritis (RA) patients will show changes in brain network connectivity and glutamate quantification in the brain and that RA patients will show changes in monocyte infiltration into the brain that are correlated with changes in sickness behaviours. This is a randomised, placebo-controlled waiting list study. All patients will be eligible for anti-TNF treatment i.e. moderate to severe active disease as defined by Physician. Participants will be randomised to immediate (fast tracked) treatment or to treatment after 6-8 weeks (the routine waiting time). The latter group will receive placebo during the treatment phase.

Detailed description

The study will involve participants aged over 18 years with RA and are scheduled to start outpatient anti-TNF treatment (with Adalimumab) as part of standard clinical care, who meet the inclusion criteria and none of the specified exclusion criteria. All will give full informed consent. This is a single-blind, randomised placebo-controlled waiting list study and after screening and consent, eligible participants will be randomised (1:1) to receive either adalimumab or placebo. The study comprises standard care screening for anti-TNF therapy (incorporated into the study to allow us to fast track screening), a total of 7 research visits and one remote visit via telephone. At Visit 1 (Day 0) and Visit 4 ((14 ± 2 days from Visit 3), participants will undergo 7T MRI and MRS Neuroimaging protocols that incorporate resting-state and task-based fMRI and glutamate MRS measures. At Visit 1A (1 - 7 days from Visit 1) and Visit 4A (1 - 7 days from Visit 4), participants will undergo an optional SPECT scanning protocol. This visit will involve a 160ml blood draw, from which monocytes will be isolated and radiolabelled before being reinjected prior to SPECT scanning.

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
DRUG	Adalimumab	Adalimumab 40mg, will be administered as a subcutaneous injection once fortnightly on four occasions. The actual Adalimumab product selected at site will be dictated by what is used in standard care.
DRUG	Placebo	Sodium chloride 0.9% for injection will be used as a placebo. An equal volume will be drawn up into a suitable sized syringe and labelled in accordance with standard practice at site. The dose will be administered as a subcutaneous injection once fortnightly on four occasions.

Timeline

• Start date: 2022-11-04
• Primary completion: 2024-11-29
• Completion: 2024-11-29
• First posted: 2021-10-22
• Last updated: 2025-01-14

Locations

2 sites across 1 country: United Kingdom