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

• Status: Not yet recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NHS Greater Glasgow and Clyde
• Collaborator: University of Glasgow
• Treatments: Adalimumab

Criteria

Inclusion Criteria:

• Adults ≥ 18 years < 75 years.

• Physician diagnosed moderate to severe RA.

• No previous biologic disease modifying antirheumatic drug therapy

• Eligible for anti-TNF treatment in line with site local requirements and selected to start adalimumab by their usual rheumatology clinical team for active RA in line with the license for adalimumab (originator or biosimilar) and local practice

• Self-reported sickness behaviour (fatigue, depression, anxiety) with one component > 4 on NRS

• Right-handed (to reduce neuroimaging heterogeneity).

• No contraindications to MRI (e.g. metal implants, claustrophobia).

• No contraindications to Adalimumab.

• Agree to use of contraception for study duration, where appropriate.

• Willing to participate and give informed consent.

• Satisfactory completion of standard pre-biologic safety screening (including but not limited to exclusion of latent TB infection according to local protocol, chest X-ray, negative HIV screen, negative Hepatitis screen antibody, negative Hepatitis B surface antigen [Hep B sAg] and negative Hepatitis B anit-core antibody [Hep B cAb]

Exclusion Criteria:

• Inability to provide written informed consent.

• Severe physical impairment (e.g. blindness, deafness, paraplegia).

• Pregnant, planning pregnancy or breast feeding.

• Serious infection including sepsis, tuberculosis and opportunistic infections such as invasive fungal infections.

• Severe liver or renal disease.

• Haemoglobin less than 100g/L

• Major confounding neurological disease including Multiple Sclerosis, Stroke, Traumatic Brain Injury, Parkinson's Disease, Alzheimer's Disease

• Previous biologic disease modifying antirheumatic drug therapy with adalimumab, etanercept, qolimumab, infliximab, certolizumab, abatacept, tocilizumab, sarilumab, rituximab, tofacitinib or upadacitinib

• Recent (within 4 weeks) use of intra-muscular or intra-articular steroid injections

• History of age-related cognitive impairment or dementia, of any severity

• Any other medicinal product that may, in the Principal Investigator's opinion, influence underlying disease activity through effects on immune and/or inflammatory responses