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

February 12, 2021 updated by: RIHassan, Assiut University

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

70

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
    • Upper Egypt
      • Assiut, Upper Egypt, Egypt
        • Assiut university Pediatric hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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.

Other Names:
  • Advil
Active Comparator: 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.
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.

Other Names:
  • Deltasone Oral or Solu-Medrol IV
Active Comparator: 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.
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.

Other Names:
  • Rheumatrex

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Investigators

  • Study Director: Safiea AF El-Deeb, PROF, Assiut University Child Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2018

Primary Completion (Anticipated)

November 11, 2021

Study Completion (Anticipated)

May 11, 2022

Study Registration Dates

First Submitted

September 28, 2018

First Submitted That Met QC Criteria

October 1, 2018

First Posted (Actual)

October 2, 2018

Study Record Updates

Last Update Posted (Actual)

February 15, 2021

Last Update Submitted That Met QC Criteria

February 12, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANCA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

There is a plan to make IPD and related data dictionaries available.

IPD Sharing Time Frame

starting in January 2021

IPD Sharing Access Criteria

through finding the research in the site of ClinicalTrials.gov

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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