Efficacy of Oral Sucrosomial Iron Supplementation in Children With Celiac Disease and Iron Deficiency or Anemia

Official title

Efficacy of Oral Sucrosomial Iron Supplementation in Children With Celiac Disease and Iron Deficiency or Anemia: a Double-blind, Randomized, Placebo-controlled Trial

Overview

Celiac disease in children is frequently associated with iron deficiency and/or iron deficiency anemia due to intestinal malabsorption and chronic inflammation. Although a gluten-free diet is the standard treatment and can restore iron balance over time, there is currently no clear evidence or consensus on the role and timing of iron supplementation in pediatric patients at diagnosis. Given the potential impact of anemia on growth and neurodevelopment, strategies that enable a faster correction of iron deficiency are clinically relevant. Sucrosomial® iron has shown improved absorption and gastrointestinal tolerability compared to conventional oral iron in adult celiac patients. This study aims to evaluate whether Sucrosomial® iron supplementation, in addition to a gluten-free diet, is more effective and safe than diet alone in achieving a faster normalization of hemoglobin and iron stores in children with newly diagnosed celiac disease. The primary objective of this randomized, double-blind, placebo-controlled, parallel-group study is to assess whether oral supplementation with Sucrosomial® iron, when added to a gluten-free diet (GFD), accelerates the normalization of iron stores and hemoglobin levels compared with GFD alone in school-age children and adolescents newly diagnosed with celiac disease presenting with hypoferritinemia and/or iron deficiency anemia. Target Study Population: Children and adolescents with celiac disease and iron deficiency or anemia due to iron deficiency. Study Duration Total study duration (per patient) will be about 6 months; total treatment duration (per patient) will be 6 months. Number of Patients: 60 planned Two typologies of patients will be included: with hypoferritinemia and with anemia due to iron deficiency. The randomization process will be stratified, so that: * 15 patients with hypoferritinemia receive active treatment and 15 patients receive placebo; * 15 patients with anemia due to iron deficiency receive active treatment and 15 patients receive placebo. The age of patients will also be considered for the randomization (to assign the correct number of product bottles).

Interventions

• Dietary supplement Sideral forte® VERUM drops
  Patients with hypoferritinemia (no anemia): * From 8 years until development (Tanner stage \<=3): 1 ml of Sideral forte® VERUM drops, equal to 14 mg of iron element; * From development (Tanner stage \>3) up to 18 years: 2 ml of Sideral forte® VERUM drops, equal to 28 mg of iron element.
• Dietary supplement Sideral forte® VERUM drops
  Patients with anemia due to iron deficiency: * From 8 years until development (Tanner stage \<=3): 2 ml of Sideral forte® VERUM drops, equal to 28 mg of iron element; * From development (Tanner stage \>3) up to 18 years: 3 ml of SiderAL FORTE oral drops, equal to 42 mg of iron element.
• Dietary supplement Sideral forte® matching PLACEBO drops
  Patients with hypoferritinemia (no anemia): * From 8 years until development (Tanner stage \<=3): 1 ml/day of PLACEBO drops; * From development (Tanner stage \>3) up to 18 years: 2 ml/day of of PLACEBO drops.
• Dietary supplement Sideral forte® matching PLACEBO drops
  Patients with anemia due to iron deficiency: * From 8 years until development (Tanner stage \<=3): 2 ml of PLACEBO drops; * From development (Tanner stage \>3) up to 18 years: 3 ml of PLACEBO drops.

Primary outcome measures

• Time to normalization of iron status [Time frame: From enrollment to the end of the treatment at 6 months]

Secondary outcome measures (12)

• Change in hemoglobin [Time frame: Baseline to 6 months]
• Change in serum ferritin [Time frame: Baseline to 6 months]
• Change in mean corpuscular volume (MCV) [Time frame: Baseline to 6 months]
• Change in mean corpuscular hemoglobin (MCH) [Time frame: Baseline to 6 months]
• Change in mean corpuscular hemoglobin concentration (MCHC) [Time frame: Baseline to 6 months]
• Change in reticulocyte count [Time frame: Baseline to 6 months]
• Change in serum iron [Time frame: Baseline to 6 months]
• Change in transferrin saturation [Time frame: Baseline to 6 months]
• Change in vitamin B12 [Time frame: Baseline to 6 months]
• Change in folate [Time frame: Baseline to 6 months]
• Change in fatigue score assessed by PedsQL™ Multidimensional Fatigue Scale [Time frame: From enrollment to the end of the treatment at 6 months]
• Changes from baseline in disease-specific quality of life measured by Coeliac Disease Dutch Questionnaire (CDDUX) [Time frame: From enrollment to the end of the treatment at 6 months]

Eligibility criteria

Inclusion criteria

• Diagnosis of CD according to the current European ESPGHAN guidelines (clinical or histological) with confirmed hypoferritinemia or iron deficiency anemia.
• Age at diagnosis of CD between 8 and 18 years (inclusive).
• Absence of oral martial supplementation in the 30 days before the diagnosis and intravenous martial supplementation in the 90 days prior to the diagnosis of CD.
• Patients who have not already started GFD before diagnosis.
• Exclusion of other causes of anemia.
• Patients (and parents/legal guardian) able to understand and willing to participate in the study, with collaborative attitude.
• Informed consent release by both parents/legal guardian.

Exclusion criteria

• Potential celiac disease.
• Hb < 8 g/dL at screening
• Other causes of anemia, hemoglobinopathies or coagulopathies.
• Active bleeding or surgery or major trauma in the last 6 months.
• Other inflammatory diseases, neoplasms or IgE mediated food allergies
• Syndromes or presence of vascular malformations
• Pregnant or lactating patients (based on self-certification by the parents and by the patient, where applicable)\*
• Patients with known or suspected allergy or hypersensitivity to the study products or any of their excipients.
• Taking oral iron-based medications in the 30 days prior to diagnosis and intravenous iron-based medications in the 90 days prior to diagnosis.
• Use of other investigational drug(s) within 30 days before study entry or during the study.
• Any other condition, illness or treatment that in the Investigator's opinion does not make the patient suitable for the study.

• Self-certification of non-pregnancy status is considered sufficient given that the product under study is a safe and well-tolerated dietary supplement that has already been tested in pregnant women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• IRCCS Istituto Giannina Gaslini, pad 16 — Genova

Publications

• Ministero della Salute "Linee di indirizzo sugli studi condotti per valutare la sicurezza e le proprietà di prodotti alimentari" - Revisione novembre 2018.
• Parisi F, Berti C, Mando C, Martinelli A, Mazzali C, Cetin I. Effects of different regimens of iron prophylaxis on maternal iron status and pregnancy outcome: a randomized control trial. J Matern Fetal Neonatal Med. 2017 Aug;30(15):1787-1792. doi: 10.1080/14767058.2016.1224841. Epub 2016 Sep 2. PMID 27588568
• Varni JW, Bendo CB, Denham J, Shulman RJ, Self MM, Neigut DA, Nurko S, Patel AS, Franciosi JP, Saps M, Verga B, Smith A, Yeckes A, Heinz N, Langseder A, Saeed S, Zacur GM, Pohl JF. PedsQL gastrointestinal symptoms module: feasibility, reliability, and validity. J Pediatr Gastroenterol Nutr. 2014 Sep;59(3):347-55. doi: 10.1097/MPG.0000000000000414. PMID 24806837
• Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care. 2001 Aug;39(8):800-12. doi: 10.1097/00005650-200108000-00006. PMID 11468499
• van Doorn RK, Winkler LM, Zwinderman KH, Mearin ML, Koopman HM. CDDUX: a disease-specific health-related quality-of-life questionnaire for children with celiac disease. J Pediatr Gastroenterol Nutr. 2008 Aug;47(2):147-52. doi: 10.1097/MPG.0b013e31815ef87d. PMID 18664865
• Varni JW, Burwinkle TM, Katz ER, Meeske K, Dickinson P. The PedsQL in pediatric cancer: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module. Cancer. 2002 Apr 1;94(7):2090-106. doi: 10.1002/cncr.10428. PMID 11932914
• Corazza GR, Villanacci V. Coeliac disease. J Clin Pathol. 2005 Jun;58(6):573-4. doi: 10.1136/jcp.2004.023978. No abstract available. PMID 15917404
• Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol. 1999 Oct;11(10):1185-94. doi: 10.1097/00042737-199910000-00019. PMID 10524652

Identifiers

NCT: NCT07563582 · CD-GAS-FESUCR

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗