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BAFF Levels and Lupus Nephritis (LN) (BAFF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04369495
Recruitment Status : Not yet recruiting
First Posted : April 30, 2020
Last Update Posted : May 4, 2020
Sponsor:
Collaborators:
ARTMEDICA
GlaxoSmithKline
Information provided by (Responsible Party):
Gloria Vasquez, Universidad de Antioquia

Brief Summary:

B-cell activating factor (BAFF), also known as B lymphocyte stimulator (BLyS) serves as a vital survival and differentiation factor for normal B-cell development. There is an inverse relationship between BAFF circulating levels and the percentage and number of circulating B cells. BAFF levels have been associated with the clinical activity of SLE in humans. BAFF plays a pathogenic role in SLE in part through T cell-dependent B cell autoantibody production. BAFF, has a role in the maintenance of memory B cells and promotes plasma cell survival. Treatment strategies involving BAFF blockade haven been studied in patients with SLE inducing overall improvement in disease activity, mainly in musculoskeletal and mucocutaneous domains leading to the approval of Belimumab for the treatment of patients with systemic lupus erythematosus without severe renal or neurological involvement.

Antibodies against CD20 molecule, anti-CD20 antibodies (Rituximab), cyclophosphamide (CYC), and mycophenolate (MMF) have all been used for the treatment of different manifestations of systemic lupus erythematosus and both moderate and severe activity. Baseline C4 level, early normalization of complement, and reduction in proteinuria have been shown to predict renal response to therapy with MMF or CYC in lupus nephritis. With Rituximab (RTX), B cell depletion has been associated with response to treatment and relapse prediction. The elevation of serum BAFF levels after B cell depletion with RTX in SLE are associated with anti-double-stranded DNA antibody levels and disease flare. The rise of BAFF is probably due to the decrease in its receptors leading to a release of BAFF and a delayed regulation of BAFF mRNA transcription, both of which could favor the re-emergence of autoreactive B cells.

It has been suggested that the rise in BAFF levels after anti-CD20 therapy might be related to flares of the disease. Additionally, the combination of anti-CD20 with anti-BAFF or antibodies against CD4, anti-CD4 antibody greatly reduces the number of splenic plasma cells in mouse models and anti-CD20 plus anti-BAFF has been proven to have a lasting benefit both in lupus-prone mice and in mice with established disease.

Currently, there is a lack of information regarding MMF or CYC and BAFF levels without the use of concomitant RTX (for CYC) and in monotherapy (for MMF). We consider that it is fundamental to know the behavior of BAFF in patients with SLE after treatment with MMF or CYC bearing in mind the proposal of multiple experts of the possible use of sequential therapy of BAFF inhibition after B-cell depletion. Knowledge of the behavior of BAFF will allow me to better understand its implications in SLE and its therapy. If our hypothesis is true maybe, we can postulate the use of sequence therapy with Belimumab after CYC o MF induction with the proposal to reduce the flares.


Condition or disease Intervention/treatment
Lupus Nephritis Other: BAFF serum levels

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: BAFF Levels After Cyclophosphamide and Mycophenolate Use in Patients With Systemic Lupus Erythematosus
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : January 2023


Group/Cohort Intervention/treatment
Cyclophosphamide
Patients with induction therapy for lupus nephritis with cyclophosphamide
Other: BAFF serum levels
BAFF levels in serum in visit 0,1,2 during induction therapy

Mycophenolate
Patients with induction therapy for lupus nephritis with mycophenolate
Other: BAFF serum levels
BAFF levels in serum in visit 0,1,2 during induction therapy




Primary Outcome Measures :
  1. Levels of BAFF [ Time Frame: Time 0, beginning of the induction therapy ]
    Levels of BAFF

  2. Levels of BAFF [ Time Frame: Time 1, 12 weeks after beginning of induction therapy ]
    Levels of BAFF

  3. Levels of BAFF [ Time Frame: Time 2, 24 weeks after beginning of induction therapy ]
    Levels of BAFF

  4. Lupus Clinical Manifestations [ Time Frame: Time 0, beginning of the induction therapy ]
    All clinical manifestations associated with SLE

  5. Lupus Clinical Manifestations [ Time Frame: Time 1, 12 weeks after beginning of induction therapy ]
    All clinical manifestations associated with SLE

  6. Lupus Clinical Manifestations [ Time Frame: Time 2, 24 weeks after beginning of induction therapy ]
    All clinical manifestations associated with SLE

  7. Serological findings [ Time Frame: Time 0, beginning of the induction therapy ]
    Serological parameters evaluated including anti-DNA

  8. Serological findings [ Time Frame: Time 1, 12 weeks after beginning of induction therapy ]
    Serological parameters evaluated including anti-DNA

  9. Serological findings [ Time Frame: Time 2, 24 weeks after beginning of induction therapy ]
    Serological parameters evaluated including anti-DNA

  10. Inflammatory cytokine levels [ Time Frame: Time 0, beginning of the induction therapy ]
    Cytokine levels IL-10, IL-12, TNF-α, IL-1β, IL-8 e IL-6

  11. Inflammatory cytokine levels [ Time Frame: Time 1, 12 weeks after beginning of induction therapy ]
    Cytokine levels IL-10, IL-12, TNF-α, IL-1β, IL-8 e IL-6

  12. Inflammatory cytokine levels [ Time Frame: Time 2, 24 weeks after beginning of induction therapy ]
    Cytokine levels IL-10, IL-12, TNF-α, IL-1β, IL-8 e IL-6


Biospecimen Retention:   Samples Without DNA
Serum


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
  • Patients with SLE diagnosis that fulfill either the 1987 American College of Rheumatology Classification Criteria for SLE, 2011 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for systemic lupus erythematosus or 2019 EULAR/ACR Lupus Classification criteria.
  • There will not be a successive recruitment of patients. Instead, there will be a deliberate recruitment aiming to maintain the proportion of patients needed for each group.

A sample will be taken for the convenience of 30 patients with lupus nephritis by Wallace and Dubois criteria. Fifteen patients under treatment with CYC and 15 patients treated with MMF are selected according to the decision of the attending physician.

Criteria

Inclusion Criteria:

  1. Patients are older than 18 years
  2. Patients that fulfill any of the available classification criteria for systemic lupus erythematosus
  3. Patients with new-onset lupus nephritis or with lupus nephritis relapse after successful remission.
  4. Patients with a diagnosis of lupus nephritis according to Wallace and Dubois criteria
  5. Patients with class III and IV lupus nephritis with or without Class V lupus nephritis.

Exclusion Criteria:

  1. Women with a positive pregnancy test
  2. Class I, II, V lupus nephritis without Class III or IV lupus nephritis
  3. Patients with an active malignancy or active treatment for malignancy.
  4. Patients with kidney disease with GFR <30ml / min
  5. Patients with severe leukopenia
  6. Patients with active infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04369495


Contacts
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Contact: Gloria Vasquez, MD, DrSc 42196446 glomavas@gmail.com
Contact: Gloria Vasquez, MD.DrSc 42196446 glomavas@gmail.com

Sponsors and Collaborators
Universidad de Antioquia
ARTMEDICA
GlaxoSmithKline
Investigators
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Principal Investigator: Gloria Vasquez, MD, DrSc Universidad de Antioquia
Publications:

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Responsible Party: Gloria Vasquez, MD, DrSc, Rheumatologyst, Prinicipal investigator, Proffesor Grupo de Inmunologia Celular e Inmunogenética. Instituto de Investigaciones Médicas. Facultad de Medicina., Universidad de Antioquia
ClinicalTrials.gov Identifier: NCT04369495    
Other Study ID Numbers: UAntioquia/GICIG/BAFF
First Posted: April 30, 2020    Key Record Dates
Last Update Posted: May 4, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gloria Vasquez, Universidad de Antioquia:
BAFF
Additional relevant MeSH terms:
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Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases