Despite advances in immunomodulatory therapies, many Psoriatic arthritis (PsA) patients experience persistent pain unrelated to clinical active joint inflammation. Recent evidence suggests the Inferior Parietal Lobule (IPL) serves as a neuroimmune hub linking central neural activity with peripheral immune dysregulation. In a prior feasibility study, a single L-IPL-targeted TMS session reduced pain and altered immune signalling in inflammatory arthritis by reducing STAT3 phosphorylation in circulating monocytes. This study builds on those findings by evaluating whether rTMS over 4 weeks can induce sustained immune reprogramming while providing meaningful pain relief.
Adults ≥ 18 years ≤ 75 years
Diagnosis of PsA according to CASPAR (Classification Criteria for Psoriatic Arthritis).
Low disease activity (no more than one joint with clinically active swelling) or remission
Chronic pain for at least 3 months and VAS (Visual Analogue Scale) pain ≥30 mm
Inability to provide written informed consent.
Severe physical impairment (e.g. blindness, deafness, paraplegia) Pregnant, planning pregnancy or breast feeding.
Severe claustrophobia precluding MRI.
Contraindications to MRI (e.g. metal implants/ pacemaker).
Parallel
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
DevicerTMS delivered to the left inferior parietal lobule at 10 Hz, 90% resting motor threshold, 1200 pulses per session, for 12 sessions over 4 weeks.
Control Repetitive Transcranial Magnetic Stimulation (rTMS)
DevicerTMS delivered to the cranial vertex using identical stimulation parameters to the active arm, serving as a control condition.
Change in STAT3 phosphorylation in circulating monocytes
Assessment of the effect of left-inferior parietal lobule (L-IPL) targeted repetitive transcranial magnetic stimulation (rTMS) on immune systems; specifically changes in circulating monocytes intracellular signalling, primarily STAT3 phosphorylation levels, assessed via flow cytometry, before and after rTMS targeting L-IPL compared with the control (vertex stimulation) condition.
Changes in genetic expression of circulating immune cells, monocytes and CD8+ T-cells, using transcriptomic assays (RNA-seq).
Change in transcriptomic signatures of circulating monocytes and CD8⁺ T-cells, measured using RNA-sequencing to evaluate treatment-related alterations in immune cell gene expression.
Changes in trained immunity set-points in monocytes and CD8+ T-cells, by investigating their epigenetic profile changes using Cleavage Under Targets and Tagmentation (CUT&TAG assay).
Changes in trained immunity set-points within circulating monocytes and CD8+T-cells, investigated by epigenetic profiling using using Cleavage Under Targets and Tagmentation (CUT\&Tag).
Changes in pain severity as measured by the Pain Number Rating Scale.
Change in pain severity assessed using the Numeric Rating Scale (0-10), where 0 indicates no pain and 10 indicates the worst pain imaginable.
Changes in pain severity as measured by Widespread Pain as part of the American College of Rheumatology Fibromyalgia scale.
Change in pain severity assessed using the Widespread Pain Index (0-19) from the American College of Rheumatology Fibromyalgia criteria, with higher scores indicating pain in a greater number of body regions.
Feasibility data on EQ-5D quality of life scores.
Feasibility of collecting EuroQol-5D-5L Questionnaire quality-of-life data assessed by the proportion of participants who complete the EQ-5D questionnaire at required study visits. The EQ-5D-5L includes five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on five levels of severity, converted into a single index score ranging from below 0 to 1.0, where higher scores indicate better health-related quality of life.
Feasibility data on participant adherence.
Feasibility of participant adherence assessed by the proportion of scheduled rTMS visits attended across the 4-week intervention period, including adherence to interim assessments such as questionnaires and 7-day pain diaries.
Feasibility data on TMS tolerability.
Feasibility of TMS tolerability assessed by the frequency and severity of TMS-related adverse events recorded at each study visit across the 4-week intervention period.
Feasibility data on protocol completion rates.
Feasibility of protocol completion assessed by the proportion of participants who complete the 4-week intervention, defined as attending the required rTMS sessions (up to two allowable missed visits) and completing key study assessments (questionnaires, blood sampling, and MRI).
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NHS Greater Glasgow and Clyde
Lead sponsor
Chief Scientist Office of the Scottish Government
Collaborator
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