Prediction of Outcome of Lupus Nephritis

Systemic Lupus Erythematosus Clinical Trial

Official title:

Validation of the Assay of Circulating Antibodies Against Glomerular Neo-autoantigens as a Surrogate Biomarker of the Development of Lupus Nephritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02403115
• Other study ID #: SLE1
• Status: Recruiting
• Start date: October 2014
• Est. completion date: November 2022

Study information

• Verified date: July 2020
• Source: Istituto Giannina Gaslini
• Contact: Gian Marco Ghiggeri, MD
• Phone: 0039 010 56362419
• Email: gmarcoghiggeri[@]ospedale-gaslini.ge.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to clarify the mechanisms involved in the formation and glomerular deposition of immune complexes in lupus nephritis.

The determination of an antibody pattern specific for systemic lupus erythematosus and lupus nephritis may also have a role in predicting disease progression in patients with systemic lupus erythematosus without renal impairment. As for the patients enrolled in the study, the determination of their antibody patterns may contribute to a more targeted and personalized treatment, allowing a prediction of disease progression and the introduction of early targeted treatments, in order to block the onset and/or progression of renal damage.

Description:

Prospective multicenter study on the validity of levels of circulating antibodies to glomerular neo-autoantigens (alpha-enolase and annexin AI) and implantable antigens (anti-DNA, histone, istone3, istone4, C1q) as a surrogate biomarker for the diagnosis of lupus nephritis.

The study will involve the collection of serum from patients with lupus nephritis at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the titration of circulating autoantibodies.

As a control the investigators will use the sera of patients with systemic lupus erythematosus without nephropathy, collected at the same time intervals.

The investigators will also assess the antibody positivity in groups of patients with rheumatologic disease similar to lupus (rheumatoid arthritis) and in patients with autoimmune nephropathy without extrarenal clinical signs.

Regarding patients with systemic lupus erythematosus the investigators will collect sera of both incident and prevalent patients in order to monitor changes in antibody levels in conjunction with the development of renal disease.

Clinical tests (renal function, complete blood count, C reactive protein (CRP), ANA, native DNA (nDNA), urine analysis) will be performed at 6, 12, 24 and 36 months and the surplus of blood samples will be used to create the serum bank of the study.

Samples will be collected in the pediatric nephrology of Giannina Gaslini Children Hospital, Genoa (coordinator centre) and in 5 rheumatological (Genoa, Pisa, Pavia, Padova, Brescia) and 6 nephrological (Milan, Genoa, Parma, Brescia, Bologna and Reggio Emilia) italian adults departments .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: November 2022
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age between 4 and 65 years

• Diagnosis of lupus nephritis-systemic lupus erythematosus (systemic lupus erythematosus, rheumatoid arthritis and membranous nephropathy for controls)

• Informed consent

Exclusion Criteria:

• Severe infections in place

• Malignancies of any current or history

• Chronic hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) positive

• Breast-feeding or pregnant

• Known hypersensitivity to drugs

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Lupus Nephritis
• Nephritis
• Systemic Lupus Erythematosus

Intervention

Other:
• Serum collection
Clinical tests (renal function, complete blood count, CRP, ANA, dsDNA, urinalysis) will be performed at fixed time intervals (6, 12, 24 and 36 months) and the surplus of blood sample will form the serum bank used for the study

Locations

Country	Name	City	State
Italy	IRCCS Giannina Gaslini Children Hospital	Genoa	Italy/GE

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Giannina Gaslini

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Bagavant H, Fu SM. Pathogenesis of kidney disease in systemic lupus erythematosus. Curr Opin Rheumatol. 2009 Sep;21(5):489-94. doi: 10.1097/BOR.0b013e32832efff1. Review. — View Citation

Bruschi M, Galetti M, Sinico RA, Moroni G, Bonanni A, Radice A, Tincani A, Pratesi F, Migliorini P, Murtas C, Franceschini F, Trezzi B, Brunini F, Gatti R, Tardanico R, Barbano G, Piaggio G, Messa P, Ravani P, Scolari F, Candiano G, Martini A, Allegri L, — View Citation

Bruschi M, Sinico RA, Moroni G, Pratesi F, Migliorini P, Galetti M, Murtas C, Tincani A, Madaio M, Radice A, Franceschini F, Trezzi B, Bianchi L, Giallongo A, Gatti R, Tardanico R, Scaloni A, D'Ambrosio C, Carnevali ML, Messa P, Ravani P, Barbano G, Bianc — View Citation

Cameron JS. Lupus nephritis. J Am Soc Nephrol. 1999 Feb;10(2):413-24. Review. — View Citation

Hanrotel-Saliou C, Segalen I, Le Meur Y, Youinou P, Renaudineau Y. Glomerular antibodies in lupus nephritis. Clin Rev Allergy Immunol. 2011 Jun;40(3):151-8. doi: 10.1007/s12016-010-8204-4. Review. — View Citation

Kramers C, Hylkema MN, van Bruggen MC, van de Lagemaat R, Dijkman HB, Assmann KJ, Smeenk RJ, Berden JH. Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular basement membrane in vivo. J Clin Invest. 1994 Aug;94(2):568-77. — View Citation

Madaio MP. The relevance of antigen binding to the pathogenicity of lupus autoantibodies. Kidney Int. 2012 Jul;82(2):125-7. doi: 10.1038/ki.2012.159. — View Citation

Waldman M, Madaio MP. Pathogenic autoantibodies in lupus nephritis. Lupus. 2005;14(1):19-24. Review. — View Citation

Yu C, Gershwin ME, Chang C. Diagnostic criteria for systemic lupus erythematosus: a critical review. J Autoimmun. 2014 Feb-Mar;48-49:10-3. doi: 10.1016/j.jaut.2014.01.004. Epub 2014 Jan 21. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Proteinuria at 12, 24 and 36 months	proteinuria measured on a 24-hour urine collection.	12, 24, 36 months
Secondary	Renal function	estimated glomerular filtration rate (eGFR) measured according to Revised Bedside Schwartz Formula (4-17 years old patients) or CKD-EPI Creatinine 2009 Equation (18-64 years old patients)	36 months