Evaluating the Role of IL-17 as an Orchestrator of Peripheral-central Cross Talk in Depressive Symptoms
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-74
SponsorNHS Greater Glasgow and Clyde
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Secukinumab
DrugInitial 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.
Bimekizumab
DrugInitial 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.
Ixekizumab
DrugInitial 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.
Placebo
DrugSodium 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.
Treatment groups
50 Participants
are divided into 1 treatment groupGroup A: Psoriatic Disease4 interventions
Trial outcomes
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).
Time frame
Week 0 to Week 6Secondary outcomes
1
Differences in the EEG amplitude during positive and negative response outcomes.
Changes in the EEG amplitude between the thalamic and NAcc learning systems before and after IL-17 antagonism.
Time frame
Week 0 to Week 62
Correlating fMRI signals with differences in EEG amplitude.
fMRI signals that correlate with the changing EEG amplitude, before and after IL17 antagonism.
Time frame
Week 0 to Week 6Other outcomes
1
Changes in fatigue following IL-17 antagonism using BRAF Severity
Symptoms measured using Bristol Rheumatoid Arthritis Fatigue Severity (BRAF Severity).
Time frame
Week 0 to Week 62
Changes in fatigue following IL-17 antagonism using PROMIS-Fatigue
Symptoms measured using Patient-Reported Outcomes Measurement Information System - Fatigue (PROMIS-Fatigue).
Time frame
Week 0 to Week 63
Changes in Hyperalgesia following IL-17 antagonism using American College of Rheumatology Fibromyalgia scale.
Symptoms measured using American College of Rheumatology Fibromyalgia scale.
Time frame
Week 0 to Week 64
Changes in Pain following IL-17 antagonism using Pain-NRS.
Symptoms measured using the Numeric Rating Scale for Pain (Pain-NRS).
Time frame
Week 0 to Week 6Sponsors and contacts
Click on the lead sponsor to view all of their trials.
NHS Greater Glasgow and Clyde
Lead sponsor
University of Glasgow
Collaborator
Medical Research Council
Collaborator
Source ClinicalTrials.gov