Clinical trial NCT01823029: Oxidative Stress and Inflammation Caused by Intravenous Iron in Crohn's Disease Patients With Iron Deficiency Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn's Disease
Keywords: Crohn's Disease
intravenous iron
iron deficiency anaemia
Oxidative Stress
inflammation
Lead sponsor: Jinling Hospital, China
Sponsor class: OTHER
Collaborators: name: Ministry of Health, China
First posted: 2013-04-04
Enrollment: 387
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Extra iron may not be necessary in the treatment of iron deficiency anemia in Crohn's Disease;Oxidative Stress and Inflammation may be Caused by Intravenous Iron in Crohn's Disease Patients With Iron Deficiency Anemia.

Detailed description: Anemia is one of the commonest extra-intestinal manifestations of Crohn's disease (CD) with a prevalence ranging from 6.2% up to 73.7%.Compared with other complications,it has been subestimated and received less attention from gastroenterologists, although,which is frequently associated with a reduced quality of life.What's more,there were not appropriate strategies for the adequate treatment of anaemia in CD either.

The anaemia in CD is caused by several factors, such as iron, folic acid or B12 deficiency, treatment with immunosuppressive drugs or sulfasalazine-induced hemolysis, and anemia of chronic disease, of which iron deficiency was one of the most important mechanisms. Additionally, erythropoietin(EPO) levels in chronic disease anemia are generally higher than in normal subjects.However, in CD anemic patients this EPO increase is inadequate in relation to the degree of anemia.Thus, in the treatment of iron deficiency anemia (IDA) in CD,EPO and iron supplementation are very common.Because intravenous(IV) iron is more effective and better tolerated than oral iron and is to be considered in patients with severe anemia (Hb\<10.0 g/dL), with intolerance or inadequate response to oral iron and/or those with active IBD. Intravenous iron administration is the route of choice when simultaneous treatment with erythropoiesis stimulat-ing agents (ESA) is considered.

But parenteral iron formulations have potential toxic effects such as triggering oxidative reactions and inflammatory reactions that may be very disadvantageous to CD patients. Free iron may provoke formation of free oxygen radicals. Although complex carbohydrate structures that cover free iron may alleviate this oxidative and inflammatory potential,it cannot be completely blocked. These suggest that parenteral iron could be a "double-edged sword" with the hematologic beneﬁts (increase in hemoglobin \[Hb\]) on the one hand, and with the risk of enhancement of systemic inﬂammation and oxidative stress on the other.

Although the oxidative potential of intravenous iron (IVI) has been studied extensively,there have been no studies about the effects of parenteral iron therapy on oxidative stress and inflammatory markers in the CD population. In this study, we compared different types and schedules of iron compounds for their effects on serum inflammatory-oxidative stress indices.

Eligibility criteria: Inclusion Criteria:

* Subjects should have a definitive diagnosis of Crohn's disease, based on WHO criteria
* Males and females ≥ 18 years old, including women who are not pregnant or lactating at the time of enrollment.
* Subjects should have a CDAI score \<150 at week 0
* Able to swallow tablets
* Are capable of providing written informed consent and obtained at the time of enrollment
* Willing to adhere to the study visit schedule and other protocol requirements.
* Subjects should have the hemoglobin： male patients\<130g/L，female patients\<120g/L.

Exclusion Criteria:

* Bacterial,viral or other microbial infection(including HIV)
* Needing orally administered corticosteroids for the treatment of other diseases. Inhaled or dermatologic preparations are acceptable.
* Previous or current use of infliximab.
* current use of prescription doses or chronic/frequent use of NSAIDs
* Treatment with narcotic pain medications. (Anti-diarrheal agents such as loperamide and diphenoxylate are permitted)
* History of pancreatitis, except for subjects with a known but removed cause(such as gallstone pancreatitis)
* History of abnormal liver function tests, including AST or ALT \>1.5 times upper limit of normal, alkaline phosphatase \>2 times upper limit of normal, total bilirubin \>2.5 mg/dL at screening (or within the previous 6 months, if known)
* History of malignancy
* Women who are pregnant or lactating at the time of enrollment, or who intend to be during the study period.
* Participation in other clinical trial within the past 6 months

Primary outcomes:
measure: haemoglobin raise to norm or not.
timeFrame: at 0 week, the first week, the second week, the third week, the fourth week
Secondary outcomes:
measure: The change of haematological inflammation marker(CRP,ESR,IL-10,IL-6,TNF-ａ,IL-1β)
timeFrame: at 0 week, the first week, the second week, the third week, the fourth week
measure: The change of haematological oxidative stress indicators(SOD,GSH-px and MDA)
timeFrame: at 0 week, the first week, the second week, the third week, the fourth week
measure: The change of patients'IBDQ and CDAI.
timeFrame: at 0 week and the fourth week
measure: relapse of anaemia
timeFrame: 12 weeks after treatment
Other outcomes:
Locations:
city: Nanjing
country: China
facility: General Surgery Institute,Jinling Hospital
state: Jiangsu
Study officials:
affiliation: General Surgery Institute,Jinling Hospital,Nanjing,Jiangsu,China
name: wei ming zhu, PhD,MD
role: PRINCIPAL_INVESTIGATOR
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