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

Sponsor
NHS Greater Glasgow and Clyde
Study ID
NCT05090124
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 74 Years
Healthy Volunteers
Not accepted

Interventions

  • Adalimumab — DRUG
    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.
  • Placebo — DRUG
    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.

Study Details

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.

Key Dates

Start date
Nov 4, 2022
Status verified
Jan 2025
Primary completion
Nov 29, 2024
Completion
Nov 29, 2024

Study Design

Enrollment
46 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: anti-TNF treatment
    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.
  • Placebo Comparator: Placebo
    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.

Primary Outcome Measure

Change in sickness score as measured using the sickness questionnaire [ Time Frame: Visit 1 (Baseline, Day 0), Visit 2 (14 ± 2 days from Visit 1 or Visit 1A), Visit 3 (14 ± 2 days from Visit 2), and Visit 4 (14 ± 2 days from Visit 3). ]

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