Evaluating the Role of IL-17 as an Orchestrator of Peripheral-central Cross Talk in Depressive Symptoms

Summary

The investigators seek clinically actionable understanding of the mechanisms that underlie depression in the context of immune mediated inflammatory diseases (IMIDs), delivered by a focused immune intervention study examining brain circuitry using state of the art imaging in the context of exquisitely specific therapeutic immune interception in human immune disease.

Glutamate concentration in the NAcc will be positively correlated with the magnitude of the inflammatory response and will be attenuated by IL-17A inhibition. Ultimately, this will be associated with an improvement in depressive symptoms.

The strength of coupling between early and late systems will be attenuated in the context of IL-17A-driven inflammation and will be correlated with less frequent switching behaviour following negative outcomes and ultimately depressive symptoms. This coupling will be re-established following IL-17 antagonism.

Patients whose depressive symptoms benefit most from IL-17A antagonism will exhibit greatest resting-state and task-specific functional connectivity between Th-NAcc.

Conditions

• Psoriatic Arthritis
• Depression
• Psoriatic Plaque

Interventions

DRUG

Secukinumab

Initial dosing of Secukinimab at week 0, 1, 2, 3, 4 and maintenance doses will be determined by the standard care team. This will be 150mg or 300mg. This will be administered by the study team once confirmed and randomisation has occurred for secukinimab/ placebo allocation.

DRUG

Bimekizumab

Initial dosing of bimkizumab at week 0 \& 4 and maintenance doses will be determined by the standard care team. This will be 160mg or 320mg. This will be administered by the study team once confirmed and randomisation has occurred for bimekizumab/ placebo allocation.

DRUG

Ixekizumab

Initial dosing of Ixekizumab at week 0 \& 4 or week 0, 2 \& 4, maintenance doses will be determined by the standard care team. The initial dose will be 160mgs then 80mg dose will either be given 2 or 4 weekly. This will be administered by the study team once confirmed and randomisation has occurred for Ixekizumab/ placebo allocation.

DRUG

Placebo

Sodium chloride 0.9% for injection will be used as a placebo. A 1ml 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 in line with the Secukinumab/ Bimekizumab/ Ixekizumab dosing regimen. No dose adjustments are permitted.

Sponsors & Collaborators

• University of Glasgow

  collaborator OTHER

• Medical Research Council

  collaborator OTHER_GOV

• NHS Greater Glasgow and Clyde

  lead OTHER

Principal Investigators

• Jonathan Cavanagh, MD, PhD · University of Glasgow

Eligibility

Min Age

18 Years

Max Age

74 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-02

Primary Completion

2027-02-28

Completion

2027-04-30

Countries

• United Kingdom

Study Locations