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

NCT ID: NCT03692416

Last Updated: 2021-02-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-11

Study Completion Date

2022-05-11

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Vasculitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The aim of this work is to assess the effect of various forms of treatment of vasculitis on C3, C4, C5a \& ANCA levels in blood, in infants \& children.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

No other parties are masked in this clinical trial.

Study Groups

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Ibuprofen

Patients in this group will receive:

Ibuprofen

* Oral
* At a dosage of 30 to 40 mg/kg/day, divided into 3 or 4 doses/day, max 2400 mg/day, given with food, in the form of suspension or tablets.
* Duration of therapy: 4 - 6 weeks.

Group Type ACTIVE_COMPARATOR

Ibuprofen

Intervention Type DRUG

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 Oral or Methylprednisolone IV

Steroids:

1. Pednisone (for mild/moderate cases):

* Oral
* Single daily morning dosage of 0.05-2.0 mg/kg/day, or in 2 - 4 divided doses, max 80 mg/d.
* Duration: 4 - 6 weeks, with gradual tapering to the lowest effective dose.
2. Methylprednisolone (for severe/acute cases):

* IV
* 10-30 mg/kg/dose (max 1 g), over 1 hr daily for 1-5 days, followed by oral prednisone, with gradual tapering to the lowest effective dose.
* The duration is variable according to the condition of the patient.

Group Type ACTIVE_COMPARATOR

Prednisone

Intervention Type DRUG

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

Patients in this group will receive:

Methotrexate

* Oral
* At a dosage of 10 to 20 mg/m2/wk (0.35 to 0.65 mg/kg/wk), max dose 25 mg/wk.
* Duration of therapy: 6 - 12 weeks.

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Advil Deltasone Oral or Solu-Medrol IV Rheumatrex

Eligibility Criteria

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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.
Minimum Eligible Age

1 Month

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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RIHassan

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Safiea AF El-Deeb, PROF

Role: STUDY_DIRECTOR

Assiut University Child Hospital

Locations

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Assiut University Pediatric Hospital

Asyut, Upper Egypt, Egypt

Site Status

Countries

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Egypt

References

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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.

Reference Type BACKGROUND
PMID: 27939215 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22913983 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 29037908 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26970490 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23271485 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27596099 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19028370 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29428808 (View on PubMed)

Related Links

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https://www.ClinicalGate.com/vasculitis-syndromes-2

Nelson Textbook of Pediatrics Expert Consult, Chapter 161, 1-8.

https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Rheumatoid-Arthritis

American College of Rheumatology (ACR) Juvenile Idiopathic Arthritis Guideline Project Plan - June 2017

Other Identifiers

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ANCA

Identifier Type: -

Identifier Source: org_study_id

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