Lupus NephritisNCT04218890
TF, TFPI and Plasmin as Novel Bio-markers in Early Diagnosis of Lupus Nephritis
An observational study of Lupus Nephritis, run by Assiut University.
Trial summary
Urinary levels of plasmin ,TF , and TFPI are all elevated in active LN patients compared to inactive LN patients and healthy controls. All four proteins correlated with systemic disease activity and renal disease activity. Read more about this study
- Who is it for?
- Ages 15 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2020to 1 Dec 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 15 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Clinical data will be gathered and SLEDAI will be calculated based on chart review .SLE patients will then classified as having either active LN (ALN) or inactive LN (ILN). Active LN is defined as active urine sediment or proteinuria (rSLEDAI > 0). Inactive LN is defined as inactive urine sediment and no proteinuria (rSLEDAI = 0).
Who may be able to join
- age >15 years
- SLE patients fullfiling ACR diagnostic criteria
Who cannot join
- Renal artery stenosis, congenital renal diseases ,renal tumor,other causes of GN
- Pregnancy.
- coagulation disorders
- DM,HTN and the other connective tissue disease
- Obesity
- CKD
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Urinary Tissue Factor (TF), Tissue Factor Pathway Inhibitor (TFPI) and Plasmin as Bio-markers in Early Diagnosis of Lupus Nephritis
Urinary levels of plasmin ,TF , and TFPI are all elevated in active LN patients compared to inactive LN patients and healthy controls. All four proteins correlated with systemic disease activity and renal disease activity. Importantly, urine plasmin performed best among the four proteins in discriminating active LN from inactive disease, even better than traditional markers, such as anti ds DNA and complement C3. Furthermore, the combination of urine plasmin and TFPI showed higher specificity and negative predictive values than urine plasmin when compared to anti-ds DNA and complement C3
Read the detailed description
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affects various organs, characterized by diverse autoantibodies production,mainly anti-DNA and anti-nuclear antibodies . It demonstrates variations in incidence,prevalence, disease activity and prognosis according to race and ethnicity . Lupus nephritis (LN) is one of the most frequent and severe clinical manifestations of SLE, it affects over 60% of SLE patients representing a leading cause of morbidity and mortality . Early diagnosis and monitoring of the disease flares are still challenging , although of the novel immunosuppressive drugs and biologics, which brought improvements in recent SLE/LN survival rates .
The American College of Rheumatology (ACR) guidelines for the treatment of lupus nephritis , recommend change in treatment if response to therapy has not been achieved after 6 months of induction therapy. However, response to therapy is not well defined. In addition, renal damage can occur within 6 months while waiting to define this response. Decision support tools could help define response at the start of induction therapy and have the potential to improve outcomes .
Use of laboratory parameters for LN such as creatinine clearance, anti-ds DNA, proteinuria, urine protein-to-creatinine ratio (U-PCR),and complement levels are undesirable. These markers are of less sensitivity and specificity for evolve renal activity and injury in LN.They are not directly correlated with kidney damage, which can arise before kidney function affection. Outbreak of nephritis may occur in any condition in absence and new rise in the level of proteinuria.
Kidney biopsy is a gold standard to assess the histological category of LN and the level of activity and chronicity in glomeruli. But, it is an invasive procedure and continual biopsies are inappropriate in the observing and follow up of LN . It may have sampling error because of extent number of glomeruli obtained for LN activity and chronicity. So , many studies are focusing on identifying non-invasive biomarkers for the early diagnosis and follow up of the disease and the therapy response.
Urine is easily collected and can reflect the underlying renal affection more accurately than serum. Therefore, urine bio-markers represent promising candidates for the early disease diagnosis and monitoring .Thus, novel urinary bio-markers, which are able to distinguish lupus kidney activity and its extremity, anticipate kidney outbreak, and observe treatment reciprocation and illness breakthrough are clearly obligatory . Urinary bio-markers are more sensitive for lupus nephritis;they can appear in urine before functional derangement .
Coagulation system disorders and hyper-coagulability state have been reported in lupus nephritis, also the frequency of thrombotic events was documented to be higher in SLE patients than in the general population, and these events were associated with poor outcome .Both thrombo-genic and thrombolytic cascades appear to be up-regulated in lupus nephritis, with proteins from both cascades appearing in the urine .
Urinary levels of plasmin ,TF and TFPI are all elevated in active LN patients compared to inactive LN patients and healthy controls. All four proteins correlated with systemic disease activity and renal disease activity. Importantly, urine plasmin performed best among the four proteins in discriminating active LN from inactive disease, even better than traditional markers, such as anti dsDNA and complement C3. Furthermore, the combination of urine plasmin and TFPI showed higher specificity and negative predictive values than urine plasmin when compared to anti-dsDNA and complement C3.
- Conditions
- Lupus Nephritis
- Being tested
- Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin
- Medical subject headings
- Lupus Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasminDiagnostic test
urinary sample
| Study group | Role | What they receive |
|---|---|---|
| SLE patients without lupus nephritis | 40 SLE patients
40SLE patients( All SLE pt. satisfied the ACR criteria for SLE diagnosis) these patients will be without any evidences of nephritis Receives: Diagnostic Test: Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin | |
| SLE patients with lupus nephritis | 40SLE patients with evidences of nephritis Receives: Diagnostic Test: Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin | |
| healthy control group | 20 healthy subjects matched age and sex with be enrolled as healthy control group Receives: Diagnostic Test: Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The diagnostic utility of tissue factor ,, tissue factor pathway inhibitor and plasmin as biomarkers for early detection of lupus nephritis (LN)
Urinay sample of 100 subjects (80 with SLE ,40 of them with LN,and 20 are healthy persons)will be collected as a morning sample\& using ELISA test to detect the level of these bio-markers in the urine of these subjects
Measured: 2023
the correlation of these bio-markers to the clinical staging , the disease activity index and revised treatment .
correlate the level of the markers with the renal biopsy staging and activity index using (International Society of Nephrology /Renal Pathology Society classification (ISN/RPS), and disease Activity Index (SLEDAI-2K \& r SLEDAI)).
Measured: 2023
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2020
- Study start1 Apr 2020 (estimated)
- Primary completion1 Apr 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lupus NephritisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- 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-control
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ayat salah, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04218890
- Sponsor's protocol ID
- ASA2
- Status last verified
- Jan 2020
- First submitted
- 28 Dec 2019
- Last updated
- 7 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Qin L, Stanley S, Ding H, Zhang T, Truong VTT, Celhar T, Fairhurst AM, Pedroza C, Petri M, Saxena R, Mohan C. Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis. Arthritis Res Ther. 2019 Jul 18;21(1):176. doi: 10.1186/s13075-019-1959-y.
PubMed 31319876Frijns R, Fijnheer R, Schiel A, Donders R, Sixma J, Derksen R. Persistent increase in plasma thrombomodulin in patients with a history of lupus nephritis: endothelial cell activation markers. J Rheumatol. 2001 Mar;28(3):514-9.
PubMed 11296951Ding H, Kharboutli M, Saxena R, Wu T. Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis. Clin Exp Immunol. 2016 Apr;184(1):11-8. doi: 10.1111/cei.12743. Epub 2016 Jan 11.
PubMed 26616478Petri M, Kasitanon N, Lee SS, Link K, Magder L, Bae SC, Hanly JG, Isenberg DA, Nived O, Sturfelt G, van Vollenhoven R, Wallace DJ, Alarcon GS, Adu D, Avila-Casado C, Bernatsky SR, Bruce IN, Clarke AE, Contreras G, Fine DM, Gladman DD, Gordon C, Kalunian KC, Madaio MP, Rovin BH, Sanchez-Guerrero J, Steinsson K, Aranow C, Balow JE, Buyon JP, Ginzler EM, Khamashta MA, Urowitz MB, Dooley MA, Merrill JT, Ramsey-Goldman R, Font J, Tumlin J, Stoll T, Zoma A; Systemic Lupus International Collaborating Clinics. Systemic lupus international collaborating clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum. 2008 Jun;58(6):1784-8. doi: 10.1002/art.23456.
PubMed 18512819
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urinary Tissue Factor (TF), Tissue Factor Pathway Inhibitor (TFPI) and Plasmin as Bio-markers in Early Diagnosis of Lupus Nephritis
- ClinicalTrials.gov ID
- NCT04218890
- Acronym / sponsor ID
- ASA2
- Conditions
- Lupus Nephritis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Apr 2020 (estimated)
- Primary completion
- 1 Apr 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 6 Jan 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.
Urinary levels of plasmin ,TF , and TFPI are all elevated in active LN patients compared to inactive LN patients and healthy controls. All four proteins correlated with systemic disease activity and renal disease activity. Importantly, urine plasmin performed best among the four proteins in discriminating active LN from inactive disease, even better than traditional markers, such as anti ds DNA and complement C3. Furthermore, the combination of urine plasmin and TFPI showed higher specificity and negative predictive values than urine plasmin when compared to anti-ds DNA and complement C3
Detailed description
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affects various organs, characterized by diverse autoantibodies production,mainly anti-DNA and anti-nuclear antibodies . It demonstrates variations in incidence,prevalence, disease activity and prognosis according to race and ethnicity . Lupus nephritis (LN) is one of the most frequent and severe clinical manifestations of SLE, it affects over 60% of SLE patients representing a leading cause of morbidity and mortality . Early diagnosis and monitoring of the disease flares are still challenging , although of the novel immunosuppressive drugs and biologics, which brought improvements in recent SLE/LN survival rates .
The American College of Rheumatology (ACR) guidelines for the treatment of lupus nephritis , recommend change in treatment if response to therapy has not been achieved after 6 months of induction therapy. However, response to therapy is not well defined. In addition, renal damage can occur within 6 months while waiting to define this response. Decision support tools could help define response at the start of induction therapy and have the potential to improve outcomes .
Use of laboratory parameters for LN such as creatinine clearance, anti-ds DNA, proteinuria, urine protein-to-creatinine ratio (U-PCR),and complement levels are undesirable. These markers are of less sensitivity and specificity for evolve renal activity and injury in LN.They are not directly correlated with kidney damage, which can arise before kidney function affection. Outbreak of nephritis may occur in any condition in absence and new rise in the level of proteinuria.
Kidney biopsy is a gold standard to assess the histological category of LN and the level of activity and chronicity in glomeruli. But, it is an invasive procedure and continual biopsies are inappropriate in the observing and follow up of LN . It may have sampling error because of extent number of glomeruli obtained for LN activity and chronicity. So , many studies are focusing on identifying non-invasive biomarkers for the early diagnosis and follow up of the disease and the therapy response.
Urine is easily collected and can reflect the underlying renal affection more accurately than serum. Therefore, urine bio-markers represent promising candidates for the early disease diagnosis and monitoring .Thus, novel urinary bio-markers, which are able to distinguish lupus kidney activity and its extremity, anticipate kidney outbreak, and observe treatment reciprocation and illness breakthrough are clearly obligatory . Urinary bio-markers are more sensitive for lupus nephritis;they can appear in urine before functional derangement .
Coagulation system disorders and hyper-coagulability state have been reported in lupus nephritis, also the frequency of thrombotic events was documented to be higher in SLE patients than in the general population, and these events were associated with poor outcome .Both thrombo-genic and thrombolytic cascades appear to be up-regulated in lupus nephritis, with proteins from both cascades appearing in the urine .
Urinary levels of plasmin ,TF and TFPI are all elevated in active LN patients compared to inactive LN patients and healthy controls. All four proteins correlated with systemic disease activity and renal disease activity. Importantly, urine plasmin performed best among the four proteins in discriminating active LN from inactive disease, even better than traditional markers, such as anti dsDNA and complement C3. Furthermore, the combination of urine plasmin and TFPI showed higher specificity and negative predictive values than urine plasmin when compared to anti-dsDNA and complement C3.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SLE patients without lupus nephritis | – | Diagnostic Test: Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin40 SLE patients 40SLE patients( All SLE pt. satisfied the ACR criteria for SLE diagnosis) these patients will be without any evidences of nephritis |
| SLE patients with lupus nephritis | – | Diagnostic Test: Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin40SLE patients with evidences of nephritis |
| healthy control group | – | Diagnostic Test: Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin20 healthy subjects matched age and sex with be enrolled as healthy control group |
Who may qualify
- Ages
- 15 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Clinical data will be gathered and SLEDAI will be calculated based on chart review .SLE patients will then classified as having either active LN (ALN) or inactive LN (ILN). Active LN is defined as active urine sediment or proteinuria (rSLEDAI > 0). Inactive LN is defined as inactive urine sediment and no proteinuria (rSLEDAI = 0).
Key inclusion criteria (2 listed)
- age >15 years
- SLE patients fullfiling ACR diagnostic criteria
Key exclusion criteria (6 listed)
- Renal artery stenosis, congenital renal diseases ,renal tumor,other causes of GN
- Pregnancy.
- coagulation disorders
- DM,HTN and the other connective tissue disease
- Obesity
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 |
|---|---|---|
| Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasminurinary sample | Diagnostic test | SLE patients with lupus nephritis, SLE patients without lupus nephritis, healthy control group |
Primary outcome
The diagnostic utility of tissue factor ,, tissue factor pathway inhibitor and plasmin as biomarkers for early detection of lupus nephritis (LN)
Time frame: 2023
Urinay sample of 100 subjects (80 with SLE ,40 of them with LN,and 20 are healthy persons)will be collected as a morning sample\& using ELISA test to detect the level of these bio-markers in the urine of these subjects
the correlation of these bio-markers to the clinical staging , the disease activity index and revised treatment .
Time frame: 2023
correlate the level of the markers with the renal biopsy staging and activity index using (International Society of Nephrology /Renal Pathology Society classification (ISN/RPS), and disease Activity Index (SLEDAI-2K \& r SLEDAI)).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2020.
- Background: PubMed 31319876Qin L, Stanley S, Ding H, Zhang T, Truong VTT, Celhar T, Fairhurst AM, Pedroza C, Petri M, Saxena R, Mohan C. Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis. Arthritis Res Ther. 2019 Jul 18;21(1):176. doi: 10.1186/s13075-019-1959-y.
- Background: PubMed 11296951Frijns R, Fijnheer R, Schiel A, Donders R, Sixma J, Derksen R. Persistent increase in plasma thrombomodulin in patients with a history of lupus nephritis: endothelial cell activation markers. J Rheumatol. 2001 Mar;28(3):514-9.
- Background: PubMed 26616478Ding H, Kharboutli M, Saxena R, Wu T. Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis. Clin Exp Immunol. 2016 Apr;184(1):11-8. doi: 10.1111/cei.12743. Epub 2016 Jan 11.
- Background: PubMed 18512819Petri M, Kasitanon N, Lee SS, Link K, Magder L, Bae SC, Hanly JG, Isenberg DA, Nived O, Sturfelt G, van Vollenhoven R, Wallace DJ, Alarcon GS, Adu D, Avila-Casado C, Bernatsky SR, Bruce IN, Clarke AE, Contreras G, Fine DM, Gladman DD, Gordon C, Kalunian KC, Madaio MP, Rovin BH, Sanchez-Guerrero J, Steinsson K, Aranow C, Balow JE, Buyon JP, Ginzler EM, Khamashta MA, Urowitz MB, Dooley MA, Merrill JT, Ramsey-Goldman R, Font J, Tumlin J, Stoll T, Zoma A; Systemic Lupus International Collaborating Clinics. Systemic lupus international collaborating clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum. 2008 Jun;58(6):1784-8. doi: 10.1002/art.23456.
- Individual participant dataSharing planned: Undecided
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Lupus Nephritis, run by Assiut University.
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 2 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: status not confirmed, as of the sponsor's last update on 7 Jan 2020. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Salwa Salah Elgendy, professor dr (01005766155, salwaelgendi@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The diagnostic utility of tissue factor ,, tissue factor pathway inhibitor and plasmin as biomarkers for early detection of lupus nephritis (LN) (time frame: 2023). The study lists 2 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 NCT04218890, which also lists 4 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 7 Jan 2020.