Establishing the Salience of Type 1 Interferon Pathway Blockade in the Central Mechanisms of SLE Related Fatigue

NCT06784076 | Not Yet Recruiting

• 1 other identifier: GN23RH258
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

Systemic Lupus Erythematosus (SLE) is a multi-system autoimmune disorder, characterised by activation of the interferon system. Of the multiple domains of this disease, patients identify fatigue as the most pervasive and disabling aspect. As many as 90% report significant levels of fatigue, a prevalence far in excess of that observed in the general population and most other chronic disorders. Moreover, its impact permeates all aspects of living as reflected by fatigue's strong relationship with impaired quality of life3 and work disability. Despite these substantial consequences, relatively little is known about this symptom and so the current dearth of accepted therapies is unsurprising. A better understanding of the underlying mechanisms of fatigue will be vital if efficacious interventions are to be developed in the future. The investigators will recruit 25 SLE patients to achieve 20 full data sets. They will attend for a baseline 7T brain scan to primarily measure basal ganglia glutamate and then receive 5 months of a pharmacological blocker that antagonises type 1 interferon receptors before completing the study with a final 7T brain scan to undertake repeat measure of basal ganglia glutamate.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Changes in basal ganglia glutamate levels

  Changes in basal ganglia glutamate levels measured by 7T MRI following pharmacological blockade of type 1 interferon receptors in SLE .

  0-18 weeks

Secondary Outcomes (2)

• Changes in dorsal attention network (DAN)

  0-18 weeks

• Changes in default mode network (DMN) - insula brain connectivity

  0-18 weeks

Other Outcomes (3)

• Changes of fatigue as measured via Functional Assessment of Chronic Illness Therapy - Fatigue Scale

  0-18 weeks

• Changes of fatigue as measured via the Patient-Reported Outcomes Measurement Information System Fatigue Scale.

  0-18 weeks

• Longitudinal modulation of the Type 1 Interferon Transcriptomic Signature in the Peripheral Immune Compartment

  0-18 weeks

Interventions

Anifrolumab DRUG

Anifrolumab 300mg intravenous infusions administered as described in the EU SmPC

Also known as: N/A (Not applicable)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

SLE Patients attending NHS Greater Glasgow \& Clyde, NHS Lanarkshire, NHS Forth Valley, NHS Tayside and NHS Grampian rheumatology department with low disease activity state aged over 18 years less than75 years. The total number of participants will be 20.

You may qualify if:

• Adults ≥ 18 years \< 65 years
• Fulfilment of the 2019 ACR (American College of Rheumatology)/EULAR (European Alliance of Associations for Rheumatology) classification criteria for SLE
• Persistent (\>3 months) and clinically significant fatigue (≥6 on numerical rating 0-10 scale measuring average level of fatigue during the past 7 days)
• Attainment of Lupus low disease activity state (LLDAS)

You may not qualify if:

• Inability to provide informed written consent
• Moderate or severe active SLE
• Severe active CNS (Central Nervous System) Lupus and Lupus Nephritis
• Contra-indications to anifrolumab
• History of malignancy
• History of recurrent infections or known risk factors for infection
• Active or chronic infection
• Concomitant biological therapies
• Hypersensitivity to anifrolumab or excipients
• Current treatment with a biologic medicine or monoclonal antibody (including B cell depleting therapies in the previous 52 weeks)
• Previous exposure to anifrolumab
• Contra-indications to MRI
• Pregnant or breast-feeding
• Females of child-bearing potential who do not agree to use an effective method of birth control until 12 weeks after the final study visit (See appendix 1).)
• Severe physical impairment (e.g. blindness, paraplegia)

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood sample. Urine sample is also taken as part of pregnancy test for female participants.

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

anifrolumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Neil Basu, MD, PhD

  neil.basu@glasgow.ac.uk

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maxine Arnott, BSc

CONTACT

07890 059695; maxine.arnott@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 13, 2025
• First Posted: January 20, 2025
• Study Start: March 17, 2025
• Primary Completion: March 17, 2025
• Study Completion (Estimated): March 15, 2027
• Last Updated: January 29, 2025

Record last verified: 2025-01