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History of Changes for Study: NCT03921398
Identifying New Therapeutic Targets for Lupus Treatment (ELUDIAL)
Latest version (submitted June 17, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 16, 2019 None (earliest Version on record)
2 April 26, 2019 Study Description, Outcome Measures, Conditions and Study Status
3 July 1, 2019 Recruitment Status, Study Status and Contacts/Locations
4 April 1, 2020 Recruitment Status, Study Status and Contacts/Locations
5 June 17, 2020 Recruitment Status, Study Status and Contacts/Locations
6 November 2, 2020 Groups and Interventions, Eligibility, Study Design and Study Status
7 June 17, 2021 Study Status
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Study NCT03921398
Submitted Date:  April 16, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: APHP180500
Brief Title: Identifying New Therapeutic Targets for Lupus Treatment (ELUDIAL)
Official Title: Identifying New Therapeutic Targets for Lupus Treatment
Secondary IDs:
Open or close this module Study Status
Record Verification: April 2019
Overall Status: Not yet recruiting
Study Start: April 24, 2019
Primary Completion: May 1, 2021 [Anticipated]
Study Completion: November 1, 2021 [Anticipated]
First Submitted: April 16, 2019
First Submitted that
Met QC Criteria:
April 16, 2019
First Posted: April 19, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
April 16, 2019
Last Update Posted: April 19, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Assistance Publique - Hôpitaux de Paris
Responsible Party: Sponsor
Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
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. Our objective 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. We hypothesize that studying LN extinction after ESRD will provide novel therapeutic targets to extinct lupus before ESRD. To this end, we 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, we 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.
Detailed Description:

Lupus is an autoimmune disease affecting mainly young women (9/1). Lupus nephritis (LN) occurs in 30% of patients 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, the 5-year survival after LN was below 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 prevent the damages of active lupus 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.

Our objective is to identify the mechanisms responsible for lupus extinction in ESRD (candidate pathways) and to propose new therapeutic options targeting those candidates.

There is an important need for treatment innovation for systemic lupus and LN. A large number of biotherapies have been developed recently based on the known pathophysiology of the disease. Despite important efforts made by the medical community, many research groups, and pharmaceutical companies, randomized clinical trials (RCT) failed to validate innovative treatment strategies for several decades. Our project proposes the identification of new treatment solutions through explorations in a field free of previous investigation in that aim.

A detailed knowledge of lupus extinction is required to understand its pathophysiology. Our study will detail the timeframe of, and the factors associated with lupus extinction after ESRD. Moreover, previous investigations had been conducted separately in different projects and mainly provided descriptive results. Then we built a global and integrative strategy of research in an attempt to embrace the subject as broadly as possible and maximize the opportunities to obtain successful outcome. Our project will investigate specific hypotheses that we developed from our experience and based on the expertise of the consortium, both in lupus and immune dysfunction and in ESRD and uremic toxins. The addition of a "without a priori" approach by a systematic screening of gene expression associated with lupus extinction in haemodialysis will allow us to propose a large panel of potential candidates to investigate further. Altogether, identifying the causes responsible for lupus extinction following ESRD is an innovative approach to discover new therapeutic targets. We hypothesize that mimicking LN extinction due to ESRD provides a unique opportunity to propose new strategies to treat active lupus and LN before ESRD. The 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.

We hypothesize that studying lupus extinction after ESRD will provide novel therapeutic targets to extinct lupus before ESRD. To this end, we propose to investigate several non-exclusive hypotheses based on previous findings: the sexual dysfunction hypothesis and the ESRD-associated immune cells dysfunction hypothesis. In parallel, we 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 on chronic haemodialysis, comparing gene expression of dialysis patients with extinct lupus versus patients with still active lupus at the time of the study.

We first propose a comparison of active and extinct lupus in patients with ESRD. Lupus patients on chronic haemodialysis in Ile-de-France (n=75) will be recruited for the 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). A specific authorization was obtained from the Scientific Board of the REIN Registry at Agence de la Biomédecine). 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.

Open or close this module Conditions
Conditions: Lupus Nephritis
Keywords: Lupus nephritis, haemodialysis
Open or close this module Study Design
Study Type: Observational [Patient Registry]
Observational Study Model: Case-Crossover
Time Perspective: Cross-Sectional
Biospecimen Retention:
Biospecimen Description:
Enrollment: 120 [Anticipated]
Number of Groups/Cohorts 2
Target Follow-Up Duration: 1 Day
Open or close this module Groups and Interventions
Groups/Cohorts Interventions
patients with ESRD
patients with active lupus prior to treatment and no ESRD
Open or close this module Outcome Measures
Primary Outcome Measures:
1. lupus extinction in patients treated by sequential haemodialysis
[ Time Frame: Inclusion ]

non-renal SELENA SLEDAI score < 4 and absence
Open or close this module Eligibility
Study Population:

Comparison of active and extinct lupus in patients with ESRD. 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.

Sampling Method: Non-Probability Sample
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria (ESRD group):

  • Age ≥ 18 years,
  • History of biopsy-proven lupus nephritis
  • All classes of lupus nephritis
  • Written informed consent
  • Affiliation to a social security regime

Exclusion Criteria (ESRD group):

  • Past-history of kidney transplantation
  • Active infection
  • Active allergy (such as hay fever)
  • Pregnant or breastfeeding women
  • Protected adults (individuals under guardianship by court order)

Inclusion criteria (non ESRD group):

  • Age ≥ 18 years,
  • Biopsy proven ACTIVE lupus nephritis
  • First event of lupus nephritis
  • No immunosuppressive therapy (including corticosteroids)
  • Written informed consent
  • Affiliation to a social security regime

Exclusion criteria (non ESRD group) :

  • Immunosuppressive treatment
  • Relapse of lupus nephritis under treatment
  • Pregnant or breastfeeding women
  • Protected adults (individuals under guardianship by court order)
Open or close this module Contacts/Locations
Central Contact Person: Eric DAUGAS, MD PhD
Telephone: 33140257101
Email: eric.daugas@aphp.fr
Central Contact Backup: Fran├žois GAILLARD, MD PhD
Telephone: 33140257101
Email: gaillard.f@protonmail.com
Study Officials: Eric DAUGAS, MD PhD
Principal Investigator
Assistance Publique - Hôpitaux de Paris
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Citations:
Links:
Available IPD/Information:

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