Lupus NephritisBAFFNCT04369495
BAFF Levels and Lupus Nephritis (LN)
An observational study of Lupus Nephritis, run by Universidad de Antioquia.
Trial summary
B-cell activating factor (BAFF), serves as a vital survival and differentiation factor for normal B-cell development. 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- BAFF serum levels
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2021to Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Patients are older than 18 years
- Patients that fulfill any of the available classification criteria for systemic lupus erythematosus
- Patients with new-onset lupus nephritis or with lupus nephritis relapse after successful remission.
- Patients with a diagnosis of lupus nephritis according to Wallace and Dubois criteria
- Patients with class III and IV lupus nephritis with or without Class V lupus nephritis.
Who cannot join
- Women with a positive pregnancy test
- Class I, II, V lupus nephritis without Class III or IV lupus nephritis
- Patients with an active malignancy or active treatment for malignancy.
- Patients with kidney disease with GFR <30ml / min
- Patients with severe leukopenia
- Patients with active infection
About this study
Official title: BAFF Levels After Cyclophosphamide and Mycophenolate Use in Patients With Systemic Lupus Erythematosus
B-cell activating factor (BAFF), serves as a vital survival and differentiation factor for normal B-cell development. 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 SLE without severe renal or neurological involvement.
Antibodies against CD20 molecule, (Rituximab), cyclophosphamide (CYC), and mycophenolate (MMF) have all been used for the treatment of different manifestations of SLE 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, reduces the number of splenic plasma cells in mouse models and 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. 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 and postulate the use of sequence therapy with Belimumab after CYC o MF induction with the proposal to reduce the flares
Read the detailed description
1.3. Research question Flares of lupus nephritis are related to the behavior of BAFF levels before, during, and after induction therapy.
- Theoretical framework 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. APRIL (a proliferation-inducing ligand) shares substantial homology with BAFF and binds to two of the three BAFF receptors (BCMA and TACI) but not to BR3. Like BAFF, APRIL has little role in the maintenance of memory B cells but does promote plasma cell survival better than does BAFF. Both BAFF and APRIL levels behave differently after B cell depletion in SLE and rheumatoid arthritis. BAFF levels have been associated with the development of systemic lupus erythematosus (SLE) in murine models and with clinical activity of SLE in humans. BAFF plays a pathogenic role in SLE in part through T cell-dependent B cell autoantibody production. 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.
Anti-CD20 antibodies (Rituximab), cyclophosphamide (CYC), and mycophenolate (MMF) have all been used for the treatment of systemic lupus erythematosus, and both moderate and severe activity. Both MMF and CYC show a significant effect on disease activity and circulating B, T, Natural Killer cells (NK), and Natural Killer T cells (NKT) cell subsets. 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 relapses. 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 messenger-RNA (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 and that repeated rituximab infusions can result in a feedback loop characterized by ever-rising BAFF levels, surges in autoantibody production and worsening of the disease. Additionally, the combination of antiCD20 with anti-BAFF or 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.
B-cell depletion therapy (BCDT) has been used in patients with refractory disease with failure to standard therapy through a combination of RTX and CYC, which showed an improvement in clinical and serological disease activity. Serological findings suggest that B cell clones committed to producing antinucleosome antibodies and anti-dsDNA have a relatively rapid turnover compared with cell clones producing other autoantibodies(30). BAFF levels rose in most patients at 3 months post BCDT. Those patients with an expanded autoantibody profile and raised BAFF levels at baseline had shorter responses to BCDT. Retreatment with BCDT may produce a more sustained clinical response.
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 to better understand its implications in SLE and its therapy.
- Hypothesis Elevated BAFF levels after induction therapy with MMF or CYC is associated with disease relapse.
- Objectives 4.1. Main objective Analyze the relationship between BAFF levels and relapses after treatment with CYC and MMF
4.2. Specific objectives
- Describe the clinical and immuno-serological characteristics of patients with lupus nephritis at weeks 0, 12, and 24 of induction therapy.
- Compare the effects of CYC and MMF on BAFF levels in patients with lupus nephritis in induction therapy
- Evaluate the association between BAFF levels and remission of lupus nephritis treated with CYC and MMF.
- Conditions
- Lupus Nephritis
- Being tested
- BAFF serum levels
- Keywords
- BAFF
- Medical subject headings
- Lupus Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAFF serum levelsOther
BAFF levels in serum in visit 0,1,2 during induction therapy
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide | Patients with induction therapy for lupus nephritis with cyclophosphamide Receives: Other: BAFF serum levels | |
| Mycophenolate | Patients with induction therapy for lupus nephritis with mycophenolate Receives: Other: BAFF serum levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of BAFF
Levels of BAFF
Measured: Time 0, beginning of the induction therapy
Levels of BAFF
Levels of BAFF
Measured: Time 1, 12 weeks after beginning of induction therapy
Levels of BAFF
Levels of BAFF
Measured: Time 2, 24 weeks after beginning of induction therapy
Lupus Clinical Manifestations
All clinical manifestations associated with SLE
Measured: Time 0, beginning of the induction therapy
Lupus Clinical Manifestations
All clinical manifestations associated with SLE
Measured: Time 1, 12 weeks after beginning of induction therapy
Lupus Clinical Manifestations
All clinical manifestations associated with SLE
Measured: Time 2, 24 weeks after beginning of induction therapy
Serological findings
Serological parameters evaluated including anti-DNA
Measured: Time 0, beginning of the induction therapy
Serological findings
Serological parameters evaluated including anti-DNA
Measured: Time 1, 12 weeks after beginning of induction therapy
Serological findings
Serological parameters evaluated including anti-DNA
Measured: Time 2, 24 weeks after beginning of induction therapy
Inflammatory cytokine levels
Cytokine levels IL-10, IL-12, TNF-α, IL-1β, IL-8 e IL-6
Measured: Time 0, beginning of the induction therapy
Inflammatory cytokine levels
Cytokine levels IL-10, IL-12, TNF-α, IL-1β, IL-8 e IL-6
Measured: Time 1, 12 weeks after beginning of induction therapy
Inflammatory cytokine levels
Cytokine levels IL-10, IL-12, TNF-α, IL-1β, IL-8 e IL-6
Measured: Time 2, 24 weeks after beginning of induction therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study startJan 2021 (estimated)
- Primary completionMar 2022 (estimated)
- Study completionJan 2023 (estimated)
Why it stopped: Legal problems with financial support, The study never began
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Lupus NephritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidad de Antioquia
- Sponsor type
- University, hospital or other
- Collaborators
- ARTMEDICA
- Responsible party
- Principal investigator, Gloria Vasquez, Universidad de Antioquia
- Investigators
- Gloria Vasquez, MD, DrSc, Principal investigator, Universidad de Antioquia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04369495
- Sponsor's protocol ID
- UAntioquia/GICIG/BAFF
- Acronym
- BAFF
- Status last verified
- May 2024
- First submitted
- 27 Apr 2020
- Last updated
- 13 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999 Jun 7;189(11):1747-56. doi: 10.1084/jem.189.11.1747.
PubMed 10359578Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, Plebani A, Lougaris V, Quinti I, Thon V, Litzman J, Schlesier M, Warnatz K, Thiel J, Rolink AG, Eibel H. Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol. 2012 Jan 1;188(1):497-503. doi: 10.4049/jimmunol.1102321. Epub 2011 Nov 28.
PubMed 22124120Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, Recta V, Zhong J, Freimuth W. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008 Aug;58(8):2453-9. doi: 10.1002/art.23678.
PubMed 18668552Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, Oregon-Romero E, Machado-Contreras JR, Munoz-Valle JF, Orozco-Lopez M, Marin-Rosales M, Palafox-Sanchez CA. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus. 2016 May;25(6):582-92. doi: 10.1177/0961203315608254. Epub 2015 Sep 29.
PubMed 26424128Vallerskog T, Heimburger M, Gunnarsson I, Zhou W, Wahren-Herlenius M, Trollmo C, Malmstrom V. Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther. 2006;8(6):R167. doi: 10.1186/ar2076.
PubMed 17092341Manzi S, Sanchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, Ginzler EM, D'Cruz DP, Doria A, Cooper S, Zhong ZJ, Hough D, Freimuth W, Petri MA; BLISS-52 and BLISS-76 Study Groups. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012 Nov;71(11):1833-8. doi: 10.1136/annrheumdis-2011-200831. Epub 2012 May 1.
PubMed 22550315Moroni G, Raffiotta F, Trezzi B, Giglio E, Mezzina N, Del Papa N, Meroni P, Messa P, Sinico AR. Rituximab vs mycophenolate and vs cyclophosphamide pulses for induction therapy of active lupus nephritis: a clinical observational study. Rheumatology (Oxford). 2014 Sep;53(9):1570-7. doi: 10.1093/rheumatology/ket462. Epub 2014 Feb 6.
PubMed 24505125Fassbinder T, Saunders U, Mickholz E, Jung E, Becker H, Schluter B, Jacobi AM. Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus. Arthritis Res Ther. 2015 Apr 3;17(1):92. doi: 10.1186/s13075-015-0603-8.
PubMed 25890338Zhao L, Jiang Z, Jiang Y, Ma N, Wang K, Zhang Y. Changes in immune cell frequencies after cyclophosphamide or mycophenolate mofetil treatments in patients with systemic lupus erythematosus. Clin Rheumatol. 2012 Jun;31(6):951-9. doi: 10.1007/s10067-012-1958-8. Epub 2012 Feb 21.
PubMed 22349930
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BAFF Levels After Cyclophosphamide and Mycophenolate Use in Patients With Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT04369495
- Acronym / sponsor ID
- BAFF / UAntioquia/GICIG/BAFF
- Conditions
- Lupus Nephritis
- Keywords
- BAFF
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Legal problems with financial support, The study never began
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Universidad de AntioquiaUniversity, hospital or other
- Collaborators
- ARTMEDICA
- Study start
- Jan 2021 (estimated)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Jan 2023 (estimated)
- First posted
- 30 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
B-cell activating factor (BAFF), serves as a vital survival and differentiation factor for normal B-cell development. 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 SLE without severe renal or neurological involvement.
Antibodies against CD20 molecule, (Rituximab), cyclophosphamide (CYC), and mycophenolate (MMF) have all been used for the treatment of different manifestations of SLE 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, reduces the number of splenic plasma cells in mouse models and 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. 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 and postulate the use of sequence therapy with Belimumab after CYC o MF induction with the proposal to reduce the flares
Detailed description
1.3. Research question Flares of lupus nephritis are related to the behavior of BAFF levels before, during, and after induction therapy.
- Theoretical framework 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. APRIL (a proliferation-inducing ligand) shares substantial homology with BAFF and binds to two of the three BAFF receptors (BCMA and TACI) but not to BR3. Like BAFF, APRIL has little role in the maintenance of memory B cells but does promote plasma cell survival better than does BAFF. Both BAFF and APRIL levels behave differently after B cell depletion in SLE and rheumatoid arthritis. BAFF levels have been associated with the development of systemic lupus erythematosus (SLE) in murine models and with clinical activity of SLE in humans. BAFF plays a pathogenic role in SLE in part through T cell-dependent B cell autoantibody production. 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.
Anti-CD20 antibodies (Rituximab), cyclophosphamide (CYC), and mycophenolate (MMF) have all been used for the treatment of systemic lupus erythematosus, and both moderate and severe activity. Both MMF and CYC show a significant effect on disease activity and circulating B, T, Natural Killer cells (NK), and Natural Killer T cells (NKT) cell subsets. 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 relapses. 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 messenger-RNA (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 and that repeated rituximab infusions can result in a feedback loop characterized by ever-rising BAFF levels, surges in autoantibody production and worsening of the disease. Additionally, the combination of antiCD20 with anti-BAFF or 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.
B-cell depletion therapy (BCDT) has been used in patients with refractory disease with failure to standard therapy through a combination of RTX and CYC, which showed an improvement in clinical and serological disease activity. Serological findings suggest that B cell clones committed to producing antinucleosome antibodies and anti-dsDNA have a relatively rapid turnover compared with cell clones producing other autoantibodies(30). BAFF levels rose in most patients at 3 months post BCDT. Those patients with an expanded autoantibody profile and raised BAFF levels at baseline had shorter responses to BCDT. Retreatment with BCDT may produce a more sustained clinical response.
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 to better understand its implications in SLE and its therapy.
- Hypothesis Elevated BAFF levels after induction therapy with MMF or CYC is associated with disease relapse.
- Objectives 4.1. Main objective Analyze the relationship between BAFF levels and relapses after treatment with CYC and MMF
4.2. Specific objectives
- Describe the clinical and immuno-serological characteristics of patients with lupus nephritis at weeks 0, 12, and 24 of induction therapy.
- Compare the effects of CYC and MMF on BAFF levels in patients with lupus nephritis in induction therapy
- Evaluate the association between BAFF levels and remission of lupus nephritis treated with CYC and MMF.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide | – | Other: BAFF serum levelsPatients with induction therapy for lupus nephritis with cyclophosphamide |
| Mycophenolate | – | Other: BAFF serum levelsPatients with induction therapy for lupus nephritis with mycophenolate |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- Patients are older than 18 years
- Patients that fulfill any of the available classification criteria for systemic lupus erythematosus
- Patients with new-onset lupus nephritis or with lupus nephritis relapse after successful remission.
- Patients with a diagnosis of lupus nephritis according to Wallace and Dubois criteria
- Patients with class III and IV lupus nephritis with or without Class V lupus nephritis.
Key exclusion criteria (6 listed)
- Women with a positive pregnancy test
- Class I, II, V lupus nephritis without Class III or IV lupus nephritis
- Patients with an active malignancy or active treatment for malignancy.
- Patients with kidney disease with GFR <30ml / min
- Patients with severe leukopenia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAFF serum levelsBAFF levels in serum in visit 0,1,2 during induction therapy | Other | Cyclophosphamide, Mycophenolate |
Primary outcome
Levels of BAFF
Time frame: Time 0, beginning of the induction therapy
Levels of BAFF
Levels of BAFF
Time frame: Time 1, 12 weeks after beginning of induction therapy
Levels of BAFF
Levels of BAFF
Time frame: Time 2, 24 weeks after beginning of induction therapy
Levels of BAFF
Lupus Clinical Manifestations
Time frame: Time 0, beginning of the induction therapy
All clinical manifestations associated with SLE
Lupus Clinical Manifestations
Time frame: Time 1, 12 weeks after beginning of induction therapy
All clinical manifestations associated with SLE
Lupus Clinical Manifestations
Time frame: Time 2, 24 weeks after beginning of induction therapy
All clinical manifestations associated with SLE
Serological findings
Time frame: Time 0, beginning of the induction therapy
Serological parameters evaluated including anti-DNA
Serological findings
Time frame: Time 1, 12 weeks after beginning of induction therapy
Serological parameters evaluated including anti-DNA
Serological findings
Time frame: Time 2, 24 weeks after beginning of induction therapy
Serological parameters evaluated including anti-DNA
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
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
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2024.
- Background: PubMed 10359578Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999 Jun 7;189(11):1747-56. doi: 10.1084/jem.189.11.1747.
- Background: PubMed 22124120Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, Plebani A, Lougaris V, Quinti I, Thon V, Litzman J, Schlesier M, Warnatz K, Thiel J, Rolink AG, Eibel H. Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol. 2012 Jan 1;188(1):497-503. doi: 10.4049/jimmunol.1102321. Epub 2011 Nov 28.
- Background: PubMed 18668552Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, Recta V, Zhong J, Freimuth W. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008 Aug;58(8):2453-9. doi: 10.1002/art.23678.
- Background: PubMed 26424128Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, Oregon-Romero E, Machado-Contreras JR, Munoz-Valle JF, Orozco-Lopez M, Marin-Rosales M, Palafox-Sanchez CA. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus. 2016 May;25(6):582-92. doi: 10.1177/0961203315608254. Epub 2015 Sep 29.
- Background: PubMed 17092341Vallerskog T, Heimburger M, Gunnarsson I, Zhou W, Wahren-Herlenius M, Trollmo C, Malmstrom V. Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther. 2006;8(6):R167. doi: 10.1186/ar2076.
- Background: PubMed 22550315Manzi S, Sanchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, Ginzler EM, D'Cruz DP, Doria A, Cooper S, Zhong ZJ, Hough D, Freimuth W, Petri MA; BLISS-52 and BLISS-76 Study Groups. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012 Nov;71(11):1833-8. doi: 10.1136/annrheumdis-2011-200831. Epub 2012 May 1.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gloria Vasquez, MD, DrSc principal investigator
Universidad de Antioquia
Questions about this trial
What is this clinical trial studying?
An observational study of Lupus Nephritis, run by Universidad de Antioquia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levels of BAFF (time frame: Time 0, beginning of the induction therapy). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04369495, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2024.