Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Rheumatoid Arthritis | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Adalimumab | Drug | — | UNRESOLVED |
| Placebo | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- anti-TNF treatment
- description
- Adalimumab 40mg, will be administered as a subcutaneous injection once fortnightly on four occasions. No dose adjustments are permitted. The actual Adalimumab product selected at site will be dictated by what is used in standard care. The single-use, pre-filled syringe will be removed from storage at 2-8oC at least 30 minutes prior to administration to allow the contents to come to room temperature. The pre-filled syringe will be visually inspected for discolouration and particulates as per the product Summary of Product Characteristics.To facilitate maintenance of the blind, the pre-filled syringe (PFS) presentation will be used. The pen presentation will not be used.
- interventionNames
- Drug: Adalimumab
- type
- PLACEBO_COMPARATOR
- label
- Placebo
- description
- Sodium chloride 0.9% for injection will be used as a placebo to adalimumab. 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. No dose adjustments are permitted. Prior to administration, the prepared placebo syringe will be visually inspected for discolouration and particulate matter prior to administration.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 74 Years
Show eligibility criteria text
Inclusion Criteria: * Adults ≥ 18 years \< 75 years. * Physician diagnosed moderate to severe RA. * No previous biologic disease modifying antirheumatic drug therapy * Usual care physician has confirmed the patient is eligible for anti-TNF treatment for active RA in line with the license for adalimumab (originator or biosimilar) and local practice subject to satisfactory completion of standard pre-biologic safety screening. Standard pre-biologic safety screening includes 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 anti-core antibody \[Hep B cAb\] Note: Participant consent to treatment with adalimumab will have been obtained by the usual care team as per standard practice at site and will be prior to any approach for this study. * Participant agrees to either immediate or delayed commencement of adalimumab. * Self-reported sickness behaviour (fatigue, depression, anxiety) with one component \> 4 on NRS * Right-handed (to reduce neuroimaging heterogeneity). * Women of Child-Bearing Potential (WoCBP) must be willing to use of effective contraception for study duration. Further information is provided in appendix 1 * Willing to participate and give informed consent for this research study. 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. * Clinically diagnosed major confounding neurological disease including Multiple Sclerosis, Stroke, Traumatic Brain Injury, Parkinson's Disease, Alzheimer's Disease or similar neurodegenerative 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 prior to Visit 1 baseline) use of intra-muscular or intra-articular steroid injections. * Contraindications to MRI (e.g. metal implants, claustrophobia). * Contraindications to Adalimumab. * Concurrent or previous use of any other medicinal product (excluding vaccinations) that may, in the Principal Investigator's opinion, influence underlying disease activity through effects on immune and/or inflammatory responses. If consenting to SPECT component, the following exclusions apply: * Haemoglobin less than 100g/L * Contraindications to SPECT protocol (e.g. hypersensitivity to Technetium or Stannous Chloride, recent Nuclear Medicine Procedure) * Unwilling not to donate body fluids such as blood, sperm etc. for at least 24 hours after SPECT imaging at visits 1A and 4A. * Unwilling to avoid close contact with children or people who are pregnant for 24 hours following SPECT imaging
References
Publications (0)
Data not yet available