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

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ClinicalTrials.gov Identifier: NCT03692416
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
RIHassan, Assiut University

Brief 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).


Condition or disease Intervention/treatment Phase
Vasculitis Drug: Ibuprofen Drug: Prednisone Drug: Methotrexate Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Masking Description: No other parties are masked in this clinical trial.
Primary Purpose: Treatment
Official Title: The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children Attending Assiut University Hospital.
Actual Study Start Date : November 11, 2018
Estimated Primary Completion Date : November 11, 2020
Estimated Study Completion Date : May 11, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vasculitis

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 Name: 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 Name: 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 Name: Rheumatrex




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   1 Month to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03692416


Contacts
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Contact: Rehab IM Alqoussy, MD 020100927262624 rehabibrahem30@gmail.com
Contact: Samia GL Abd El-Moety, PROF 0201008772143 abdelmoty99@yahoo.com

Locations
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Egypt
Assiut University Pediatric Hospital Recruiting
Assiut, Upper Egypt, Egypt
Contact: Rehab IM Alqoussy, MD    020100927262624    rehabibrahem30@gmail.com   
Sponsors and Collaborators
Assiut University
Investigators
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Study Director: Safiea AF El-Deeb, PROF Assiut University Child Hospital

Additional Information:
Publications:

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Responsible Party: RIHassan, Principal investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03692416     History of Changes
Other Study ID Numbers: ANCA
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: There is a plan to make IPD and related data dictionaries available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: starting in January 2021
Access Criteria: through finding the research in the site of ClinicalTrials.gov
URL: http://rehabibrahem@gmail.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RIHassan, Assiut University:
C3,C4, C5a & ANCA
Additional relevant MeSH terms:
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Vasculitis
Vascular Diseases
Cardiovascular Diseases
Prednisone
Ibuprofen
Methylprednisolone
Methotrexate
Complement System Proteins
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic