Identifying New Therapeutic Targets for Lupus Treatment

NCT03921398 | Completed DMC

• 1 other identifier: APHP180500
• Study Type: observational
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

Lupus is an autoimmune disease affecting mainly young women (9/1). Lupus nephritis (LN) occurs in 30% of the cases of lupus and is associated with end stage renal disease (ESRD) in 17 to 25% of cases after 10 years. Overall, nearly 7% of lupus patients will develop ESRD due to LN. Historically, 5-year survival after LN was lower than 20%. Nowadays, 45% of patients suffer from multiple relapses that are associated with an intermediate risk of ESRD. When ESRD occurs, lupus activity decreases progressively to reach a stable extinct state. At this stage it is possible to stop all medications to control lupus, without any flare of lupus activity. Lupus extinction following ESRD corresponds to a state of complete remission. Obtaining such a result before ESRD would avoid damages to several organs and side effects of immunosuppressive therapy. Understanding the mechanisms responsible for lupus extinction following ESRD is an innovative approach to decipher lupus pathophysiology. The objective of the study is to identify the mechanisms responsible for lupus extinction and to propose new therapeutic options based on these new mechanisms. Mechanisms responsible for lupus extinction are unknown. Lupus extinction depends on the duration of ESRD. Accumulation of several toxins that kidneys would normally eliminate in the urine is a hallmark of ESRD. Such toxins are called "uremic toxins" since they accumulate during "uremia" (ESRD). They affect biological systems such as fertility and immunity that are both closely related to lupus pathophysiology. The investigators hypothesize that studying LN extinction after ESRD will provide novel therapeutic targets to extinct lupus before ESRD. To this end, they will investigate several non-exclusive hypotheses based on previous findings of our consortium, or issued from clinical observations: the sexual dysfunction hypothesis and the ESRD-associated immune cells dysfunction hypothesis. In parallel, they will conduct an open screening of new mechanisms underlying the lupus extinction through the characterization of the differential gene expression profile associated with lupus extinction in patients undergoing dialysis.

Conditions

Lupus Nephritis

Keywords

Lupus nephritis; haemodialysis

Outcome Measures

Primary Outcomes (1)

• Nombre of patients treated by sequential haemodialysis with lupus extinction

  non-renal SELENA SLEDAI score \< 4 and absence

  Inclusion

Study Arms (3)

Patients with ESRD

Patients with history of biopsy-proven lupus nephritis (all classes of lupus nephritis)

Patients with active lupus prior to treatment and no ESRD

Patients with biopsy-proven ACTIVE lupus nephritis

Healthy individuals

Healthy individuals

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Lupus patients on chronic haemodialysis in Ile-de-France (n=75) will be recruited for biological and clinical comparison between patients with persistent lupus activity to those with extinct lupus. These dialysis patients have been identified from the national REIN registry, which prospectively collects data for all incident patients undergoing renal replacement therapy (dialysis or kidney transplantation). Additionally, patients with active lupus prior to treatment and no ESRD will serve as a "positive control" group (n=45) for markers of cellular activation and blood transcriptomic profile during lupus nephritis. Healthy controls are required to establish reference values for assays specifically developed for the ELUDIAL study.

You may qualify if:

• For the group of 75 patients on hemodialysis
• Age ≥ 18 years,
• History of biopsy-proven lupus nephritis (all classes of lupus nephritis)
• For the group of 45 patients with active lupus, not on hemodialysis
• Age ≥ 18 years,
• Biopsy-proven ACTIVE lupus nephritis
• For the group of 20 healthy individuals
• Age ≥ 18 years

You may not qualify if:

• For the group of 75 patients on hemodialysis
• No written informed consent
• Past-history of kidney transplantation
• Active infection
• Active allergy (such as hay fever)
• Pregnant or breastfeeding women
• Non-affiliation to a social security regime
• Protected adults (individuals under guardianship by court order)
• For the group of 45 patients with active lupus, not on hemodialysis
• No written informed consent
• Immunosuppressive therapy (except corticosteroids)
• Corticosteroids pulse before renal biopsy
• Pregnant or breastfeeding women
• Non-affiliation to a social security regime
• Protected adults (individuals under guardianship by court order)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Hôpital Bichat

Paris, 75018, France

Location

Related Publications (1)

• Simon Q, Gaillard F, Tchen J, Bachelet D, Sacre K, Peoc'h K, Jourde-Chiche N, Daugas E, Charles N. Immune characterization of lupus nephritis patients undergoing dialysis. J Transl Autoimmun. 2025 May 2;10:100290. doi: 10.1016/j.jtauto.2025.100290. eCollection 2025 Jun.

  PMID: 40453547 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood and saliva samples Feces samples

MeSH Terms

Conditions

Lupus Nephritis

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Eric DAUGAS, MD PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 19, 2019
• Study Start: June 18, 2019
• Primary Completion: August 11, 2022
• Study Completion: August 11, 2022
• Last Updated: July 21, 2023

Record last verified: 2023-07

Locations

FR (1)