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

赞助:

合作者:

信息的提供 (责任方):

RIHassan，Assiut University

追踪信息

首次提交日期 ^ICMJE

September 28, 2018

首次发布日期e ^ICMJE

October 2, 2018

最后更新发布日期

October 2, 2018

预计研究开始日期 ^ICMJE

November 11, 2018

预计主要完成日期

November 11, 2020 (主要结果测量的最终数据收集日期)

目前主要观察指标 ^ICMJE

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.

原始主要观察测量 ^ICMJE

与当前相同

目前的二级观察 ^ICMJE

[ Time Frame: ]

描述性信息

简略标题 ^ICMJE

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

正式标题 ^ICMJE

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

简要概况

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).

详细说明

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.

研究类型 ^ICMJE

Interventional

研究阶段

Phase 3

研究设计 ^ICMJE

分配: Randomized
干预模型: Parallel Assignment
干预模型描述: 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.
盲法: Interventional
盲法描述:No other parties are masked in this clinical trial.
主要目的: Treatment

适用条件 ^ICMJE

干预项目 ^ICMJE

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.
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.
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.

研究工具

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.
Active Comparator: Prednisone Oral or Methylprednisolone IV
Steroids: 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. 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.
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.

招募信息

招募状态 ^ICMJE

Not yet recruiting

预计入组 ^ICMJE

原始预计入组 ^ICMJE

与当前相同

预计研究完成日期

May 11, 2021

预计主要完成日期

November 11, 2020 (主要结果测量的最终数据收集日期)

合格标准 ^ICMJE

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.

性别

参与研究的性别:

All

年龄

最小年龄：1 Month ，最大年龄：17 Years

接受健康的志愿者

没有

可入组国家 ^ICMJE

管理信息

数据检测委员会

研究涉及美国FDA监管的产品

研究美国FDA监管的药品: No
研究涉及美国FDA监管的设备产品: No

IPD 共享声明

计划分享 IPD:

Yes

责任方

RIHassan，Assiut University

研究赞助商 ^ICMJE

Assiut University

合作者 ^ICMJE

研究员 ^ICMJE

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

PRS 账户

Assiut University

验证日期

September 2018

^ICMJE 国际医学期刊编辑委员会和世界卫生组织 ICTRP 要求的元素

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