The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children

Vasculitis Clinical Trial

Official title:

The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children Attending Assiut University Hospital.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03692416
• Other study ID #: ANCA
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 11, 2018
• Est. completion date: May 11, 2022

Study information

• Verified date: February 2021
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Vasculitis denotes affection of small to medium sized vessels by polyangitis. Antineutrophil cytoplasmic antibodies (ANCA) are immunoglobulin G (IgG) autoantibodies directed against constituents of neutrophil granules leading to neutrophil degeneration which results in cell apoptosis known as "Natoptosis" (NaTosis) of the cells. These lead to vessel endothelial cell damage. So that, ANCA formation seems to be the basic reaction in vasculitis.

Complement activation at C3 and C4 was thought to be involved in renal damage ANCA associated vasculitis (AAV).

Description:

Vasculitis syndromes include: Henoch-Schonlein Purpura (HSP), connective tissue disorders e.g. Systemic Lupus Erythematosus (SLE), Rheumatoid arthritis...etc; where small vessels are mainly involved in the process of vasculitis. Vasculitis syndromes also include Kawasaki disease where also medium sized vessels are also included. Other vasculitis syndromes are also reported.

ANCA associated vasculitis may be due complex interplay of genetic risks, environmental or infection trigger or adaptive immunity leading to insufficient regulation of B cells with pathogenic ANCA generation and neutrophil activation (AAV).

Complement activation at C3 and C4 was involved in organ damage, especially renal, in AAV at the alternative complement pathway, factor B and properdin component colocalized with C3 complement in the endothelium of the blood vessels.

Furthermore, the common complement pathway was activated as reflected by increased C5a levels. This suggests that both the alternative and common complement pathways are involved in some cases of vasculitis. Furthermore a decrease in these activation factors was observed during remission of vasculitis. This may denote clearance of the degradation of cell component that were blocking inactive vasculitis. In addition, many studies noticed strong increased plasma levels of the anaphlatoxin C5a that has a strong proinflammatory activity on the endothelium of vessels that may be related to disease severity. So much so, that inhibition of C5a levels by immunologic inhibitors may have a therapeutic role in some forms of ANCA positive vasculitis.

Various treatment forms have been used for vasculitis syndromes.

• Drugs used in treatment of Juvenile Idiopathic Arthritis (JIA) are:

1. Non-steroidal Anti-inflammatory Drugs (NSAIDs) such as Salicylates e.g. Aspirin, Selective COX-2 inhibitors e.g. Celecoxib & Non-Selective COX-2 inhibitors e.g. Naproxen.

2. Non-biologic Disease-Modifying Anti-rheumatic drugs such as Methotrexate.

3. Biologic Disease-Modifying Anti-rheumatic Drugs such as Infliximab.

4. Oral or parenteral Glucocorticoids such as Methylprednisolone (According to American College of Rheumatology).

• In cases of SLE, the American College of Rheumatology (ACR) recommended corticosteroids in the 1st place and change to or add Biologic Disease-Modifying Anti-rheumatic Drugs Agents such as Rituximab.

• Regarding Henoch-Schonlein Purpura vasculitis, 70% of cases are self-limited. only cases with suspected renal involvement e.g. hematuria, hypertension, headache or proteinuria are to be treated with sreroids.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: May 11, 2022
• Est. primary completion date: November 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

Inclusion Criteria:

• Infants & children with vasculitis attending Assiut University Child Hospital (AUCH), aged > 1 mo. - 17yr. of both genders will be included during 2 years of study.

Exclusion Criteria:

• Those cases aged less than one month will be excluded from the study.

Related Conditions & MeSH terms

• Vasculitis

Intervention

Drug:
• Ibuprofen
Infants and children with vasculitis attending AssiutU, aged > 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests & Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Ibuprofen for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.
• Prednisone
Infants and children with vasculitis attending AssiutU, aged > 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests & Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Steroids for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.
• Methotrexate
Infants and children with vasculitis attending AssiutU, aged > 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests & Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Methotrexate for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.

Locations

Country	Name	City	State
Egypt	Assiut University Pediatric Hospital	Assiut	Upper Egypt

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (8)

Chen SF, Wang FM, Li ZY, Yu F, Chen M, Zhao MH. The functional activities of complement factor H are impaired in patients with ANCA-positive vasculitis. Clin Immunol. 2017 Feb;175:41-50. doi: 10.1016/j.clim.2016.11.013. Epub 2016 Dec 6. — View Citation

Gou SJ, Yuan J, Chen M, Yu F, Zhao MH. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2013 Jan;83(1):129-37. doi: 10.1038/ki.2012.313. Epub 2012 Aug 22. — View Citation

Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmun Rev. 2017 Dec;16(12):1246-1253. doi: 10.1016/j.autrev.2017.10.009. Epub 2017 Oct 14. Review. — View Citation

Jarrot PA, Kaplanski G. Pathogenesis of ANCA-associated vasculitis: An update. Autoimmun Rev. 2016 Jul;15(7):704-13. doi: 10.1016/j.autrev.2016.03.007. Epub 2016 Mar 9. Review. — View Citation

Kallenberg CG, Heeringa P. Complement is crucial in the pathogenesis of ANCA-associated vasculitis. Kidney Int. 2013 Jan;83(1):16-8. doi: 10.1038/ki.2012.371. — View Citation

Noone D, Hebert D, Licht C. Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement. Pediatr Nephrol. 2018 Jan;33(1):1-11. doi: 10.1007/s00467-016-3475-5. Epub 2016 Sep 5. Review. — View Citation

Pipitone N, Salvarani C. The role of infectious agents in the pathogenesis of vasculitis. Best Pract Res Clin Rheumatol. 2008 Oct;22(5):897-911. doi: 10.1016/j.berh.2008.09.009. Review. — View Citation

von Borstel A, Sanders JS, Rutgers A, Stegeman CA, Heeringa P, Abdulahad WH. Cellular immune regulation in the pathogenesis of ANCA-associated vasculitides. Autoimmun Rev. 2018 Apr;17(4):413-421. doi: 10.1016/j.autrev.2017.12.002. Epub 2018 Feb 9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The serum levels of C3, C4 & C5a as an indicator of its therapeutic effect.	An initial estimation as well as follow up estimation after treatment for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.	2 years

External Links

•   American College of Rheumatology (ACR) Juvenile Idiopathic Arthritis Guideline Project Plan - June 2017
•   Nelson Textbook of Pediatrics Expert Consult, Chapter 161, 1-8.