Clinical trial NCT02760940: Anemia in Inflammatory Bowel Disease
Official title: Anemia Treatment in Inflammatory Bowel Disease: Predictive Factors of Response to Oral Iron Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anemia
Bowel Diseases, Inflammatory
Keywords: Inflammatory bowel diseases
Anemia
Crohn's disease
Ulcerative colitis
Oral iron
Quality of life
Lead sponsor: Federal University of Juiz de Fora
Sponsor class: OTHER
First posted: 2016-05-04
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Anemia is a clinical manifestation, which is commonly observed in patients with inflammatory bowel disease, and it accounts for significant loss in the quality of life of these patients. The aim of the current study is to assess the effect of orally administered iron treatment, as well as its response predictors in patients with inflammatory bowel disease who are in remission and present anemia. The study will recruit 100 patients with Crohn's disease (CD) and 100 patients with ulcerative colitis (UC) diagnosed and regularly monitored in the Inflammatory Bowel Disease Center at the University Hospital of the Federal University of Juiz de Fora, for clinical, hematological, biochemical and immunological assessment. Blood samples will be collected (10 ml) and the following tests will be performed in all the anemia patients (in remission) at the beginning of the treatment and 8 weeks later: complete blood count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), erythrocyte sedimentation rate (ESR) , transferrin saturation index, ferritin, serum iron, hepcidin, quantitative C-reactive protein (CRP), interleukin-6 (IL-6)) and fecal calprotectin. In addition, quality of life, anxiety and depression and fatigue questionnaires will be applied to the patients (IBDQ, HAD and Chalder). The World Health Organization (WHO) criteria will be used to diagnose anemia, therefore, hemoglobin lower than 12 g/dl for women and 13g/dl for men will be considered anemia; hemoglobin lower than 10 g/dl will be considered severe anemia. Patients with mild and moderate anemia in remission will be initially treated with oral iron (oral liposomal iron) and the occurrence of possible symptoms related to oral iron intolerance will be assessed, as well as the patients' disease activity level and quality of life. The patients in follow-up will be subjected to new laboratory tests after the eighth oral iron treatment week. The results of the current study are expected to help assessing the oral iron efficacy and response predictors, as well as the side effects of the treatment and its impact on the quality of life of patients.

Detailed description: 1. Study Design:

   Two hundred (200) patients with inflammatory bowel disease in remission - 100 patients with Crohn's disease and 100 patients with ulcerative colitis - will be randomly selected.

   The patients will be informed that their participation in the study will generate no expense or financial benefit to them. Any doubts they may have about the study will be clarified and they will be free to participate in it or not. Their refusal will not result in any penalty or change in the way they will be served. They may withdraw their consent or discontinue their participation at any time.

   Laboratory tests will be conducted at the University Hospital, according to the follow-up routine applied to patients with inflammatory bowel disease, and they will represent no risk to health different than that of common blood tests.

   The study protocol will be submitted to the Research Ethics Committee of the University Hospital for evaluation. All patients included in the study will sign a free and informed consent form. The patients will be assessed according to eligibility criteria and their demographic data (age, gender) and body weight will be recorded at the first visit. They will undergo an interview to assess symptoms and possible disease activity one week before the beginning of the treatment. They will also fill out a questionnaire about quality of life, anxiety and depression and another one about fatigue before and after the treatment. Only patients who have completed the 8-week treatment will be included in the study.

   Blood samples (10ml) will be collected for hematological, biochemical and immunological assessments, after the treatment. The following hematological and biochemical tests will be performed in patients with anemia: complete blood count, MCV, MCH, MCHC, ferritin, transferrin saturation index, hepcidin, quantitative CRP, IL-6 and fecal calprotectin.

   The blood collection will be performed by a biochemistry resident at the University Hospital of Juiz de Fora, as well as the examinations, which will be done under the supervision of biochemistry professors of the University Hospital residency program.

   All patients in the study will be subjected to the following tests: a. clinical assessment; b. questionnaire on quality of life c. questionnaire on fatigue d. questionnaire on anxiety and depression e. biochemical assessment; f. ileocolonoscopy with biopsy for histopathological study.
2. Study flowchart

   1. Phase I

      * Patient selection
      * Clinical, biochemical, colonoscopic and histopathological assessment
      * Assessment of IBDQ, HAD and Fatigue scales
   2. Phase II

      * Supplementation with oral iron
      * Monitoring of complications
   3. Phase III

      * Clinical, biochemical, colonoscopic and histopathological reassessment
      * Reassessment of IBDQ, HAD and Fatigue scales
      * Study completion
3. Statistical analysis The collected data will be analyzed by a specific statistical software (SPSS -Statistical Package for Social Sciences™, version 21.0).

The patients will be divided in two groups (mild and moderate anemia) for data analysis, according to their hemoglobin levels. The comparisons between groups, as well as the possible relations between socio-demographic and clinical variables, and changes in IBDQ, HAD and fatigue scales will be analyzed through parametric Student's t-test, Chi-square test or nonparametric Mann-Whitney test, whenever appropriate. Univariate and multivariate logistic analyses will be performed to identify possible independent predictors of oral iron response within the entire group.

The results will be presented as odds ratio (OR) and 95% confidence interval (CI). The statistical significance level will be set at P \<0.05, for comparison.

Eligibility criteria: Inclusion criteria:

* Diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis ) in remission
* Anemia

Exclusion criteria:

* Pre-existing liver disease
* Kidney failure
* Clinically significant pulmonary disease
* Systemic infection
* Pregnancy
* Current history of any type of malignancy (except skin)
* Gastrectomy
* Total colectomy or extensive intestinal resection (\> 100 cm )
* Inflammatory bowel disease activity
* Severe anemia.

Primary outcomes:
measure: Hemoglobin level improvement
timeFrame: 8 weeks
Secondary outcomes:
measure: Improvement of quality of life
timeFrame: 8 weeks
measure: Improvement of fatigue
timeFrame: 8 weeks
measure: Activation of inflammation
timeFrame: 8 weeks
measure: Improvement of anxiety and depression
timeFrame: 8 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Federal University of Juiz de Fora
name: Carla VA Antunes, MSc. MD
role: PRINCIPAL_INVESTIGATOR
References:
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