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

NCT06786936 | Recruiting

• 1 other identifier: GN22MH376
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Changes in glutamate concentration in the NAcc as measured by 7T MRS.

  Changes in glutamate concentration in the NAcc as measured by 7T MRS, from Week 0 to Week 6 (before and after IL17 antagonism).

  Week 0 to Week 6

Secondary Outcomes (2)

• Differences in the EEG amplitude during positive and negative response outcomes.

  Week 0 to Week 6

• Correlating fMRI signals with differences in EEG amplitude.

  Week 0 to Week 6

Other Outcomes (18)

• Changes in fatigue following IL-17 antagonism using BRAF Severity

  Week 0 to Week 6

• Changes in fatigue following IL-17 antagonism using PROMIS-Fatigue

  Week 0 to Week 6

• Changes in Hyperalgesia following IL-17 antagonism using American College of Rheumatology Fibromyalgia scale.

  Week 0 to Week 6

Study Arms (1)

Psoriatic Disease

Encompasses both Psoriatic Arthritis and and Plague Psoriasis .

Drug: Secukinumab; Drug: Bimekizumab; Drug: Ixekizumab; Drug: Placebo

Interventions

Secukinumab DRUG

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.

Also known as: N/A (Not applicable)

Psoriatic Disease

Bimekizumab DRUG

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.

Also known as: N/A (Not applicable)

Psoriatic Disease

Ixekizumab DRUG

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.

Also known as: N/A (Not applicable)

Psoriatic Disease

Placebo DRUG

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.

Also known as: N/A (Not applicable)

Psoriatic Disease

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

50 participants with active PsD attending clinics in NHS Greater Glasgow and Clyde, NHS Grampian, NHS Lothian, NHS Tayside, NHS Lanarkshire, NHS Forth Valley starting IL-17 antagonism as part of their usual care by either their NHS dermatology clinical care team for psoriasis, or NHS rheumatology clinical care team for PsA, and in line with the licence and SMC/NICE guidance for these agents. The decision to prescribe anti-IL17 treatment for active PsD will be made by the patients' clinical team in advance, and independently, of the study.

You may qualify if:

• Adults ≥18 years \< 75years
• Diagnosis of PsO or PsA, made by a dermatologist or rheumatologist.
• Selected to start secukinumab/ bimekizumab/ Ixekizumab as part of their standard clinical care by their usual dermatology team for PsO or rheumatology clinical team for PsA in line with the license for secukinumab/ bimekizumab/ Ixekizumab and NICE/SMC criteria.
• No contraindications to MRI (for example metal fragments or implantable devices not compatible with MRI. (no extra x-ray images will be obtained to check placement of metal fragments or clips insitu. Existing images may be used to check for possible contraindications)
• Recent (but not within 4 weeks prior baseline) use of intra-muscular or intra-articular steroid injections
• Women of Child-Bearing Potential (WoCBP) must be willing to use effective contraception for study duration. Further information is provided in appendix 1.
• Willing to participate and give informed consent

You may not qualify if:

• Inability to provide written informed consent
• Severe physical impairment (e.g., blindness, deafness, paraplegia).
• Clinically important, active infections e.g. active TB
• History of inflammatory bowel disease
• Pregnant or breast feeding
• Severe claustrophobia precluding MRI
• Contraindications to 7T MRI (metal implants in the ears, head or neck, microbladed/ tattooed eyebrows, metal fragments in the eyes)
• Confounding neurological disease including MS, Stroke, Traumatic Brain Injury
• Previous exposure to IL-17A, IL-17A/F, IL-17R inhibitors or IL-23 p19/p40 inhibitors in the last 6 months
• Hypersensitivity to any of the excipients in secukinumab/ bimekizumab/ ixekizumab.
• Any reason which, at the investigator's discretion, would make them unsuitable to take part in the study.

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator
• Medical Research Council: collaborator

Study Sites (1)

Queen Elizabeth University Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be used for peripheral immunophenotyping. This will include the capacity for future proteomic analysis, transcriptomic analysis, epigenetic analysis and flow cytometry.

MeSH Terms

Conditions

Arthritis, Psoriatic; Depression

Interventions

secukinumab; bimekizumab; ixekizumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Behavioral Symptoms; Behavior

Study Officials

• Jonathan Cavanagh, MD, PhD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maxine Arnott, BSc

CONTACT

07890 059695; maxine.arnott@glasgow.ac.uk

Neil Basu, MD, PhD

CONTACT

neil.basu@glasgow.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 22, 2025
• Study Start: June 2, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)