Efficacy of Oral Sucrosomial Iron Supplementation in Children With Celiac Disease and Iron Deficiency or Anemia
Efficacy of Oral Sucrosomial Iron Supplementation in Children With Celiac Disease and Iron Deficiency or Anemia: a Double-blind, Randomized, Placebo-controlled Trial
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).
Visão geral do estudo
Status
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Marco Crocco, MD, PhD
- Número de telefone: +3901056362350
- E-mail: marcocrocco@gaslini.org
Locais de estudo
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Italy
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Genova, Italy, Itália, 16143
- Recrutamento
- IRCCS Istituto Giannina Gaslini, pad 16
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Contato:
- Marco Crocco, MD, PhD
- Número de telefone: +3901056363620
- E-mail: marcocrocco@gaslini.org
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-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
- Adulto
Aceita Voluntários Saudáveis
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Sideral forte® VERUM drops for oral intake in addition to GFD
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Patients with hypoferritinemia (no anemia):
Patients with anemia due to iron deficiency:
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Comparador de Placebo: Sideral forte® matching PLACEBO drops for oral intake in addition to GFD
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Patients with hypoferritinemia (no anemia):
Patients with anemia due to iron deficiency:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Time to normalization of iron status
Prazo: From enrollment to the end of the treatment at 6 months
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Time from baseline (defined as the time from diagnosis of celiac disease) to the first documented normalization of iron status. Normalization is defined as:
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone. |
From enrollment to the end of the treatment at 6 months
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in hemoglobin
Prazo: Baseline to 6 months
|
Change in hemoglobin (Hb) levels (gr/dl) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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|
Change in serum ferritin
Prazo: Baseline to 6 months
|
Change in serum ferritin levels (ng/ml) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in mean corpuscular volume (MCV)
Prazo: Baseline to 6 months
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Change in mean corpuscular volume (MCV) (fL) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in mean corpuscular hemoglobin (MCH)
Prazo: Baseline to 6 months
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Change in mean corpuscular hemoglobin (MCH) (pg) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in mean corpuscular hemoglobin concentration (MCHC)
Prazo: Baseline to 6 months
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Change in mean corpuscular hemoglobin concentration (MCHC) (g/L) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in reticulocyte count
Prazo: Baseline to 6 months
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Change in reticulocyte count (reticulocyte/mmc) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in serum iron
Prazo: Baseline to 6 months
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Change in serum iron levels (ug/dl) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in transferrin saturation
Prazo: Baseline to 6 months
|
Change in transferrin saturation (%) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in vitamin B12
Prazo: Baseline to 6 months
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Change in vitamin B12 levels (pg/ml) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in folate
Prazo: Baseline to 6 months
|
Change in folate levels (ng/ml) from baseline to 6 months.
Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone.
|
Baseline to 6 months
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Change in fatigue score assessed by PedsQL™ Multidimensional Fatigue Scale
Prazo: From enrollment to the end of the treatment at 6 months
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Change from baseline to 6 months in fatigue, assessed using the PedsQL™ Multidimensional Fatigue Scale total score. The PedsQL™ Multidimensional Fatigue Scale is a validated pediatric questionnaire available in age-appropriate versions. Scores range from 0 to 100, with higher scores indicating lower levels of fatigue. Comparisons will be performed between participants receiving oral Sucrosomial® iron supplementation plus a gluten-free diet (GFD) and those receiving GFD alone. |
From enrollment to the end of the treatment at 6 months
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Changes from baseline in disease-specific quality of life measured by Coeliac Disease Dutch Questionnaire (CDDUX)
Prazo: From enrollment to the end of the treatment at 6 months
|
To evaluate the effect of oral supplementation with Sucrosomial® iron, as an add-on to a gluten-free diet (GFD), compared with placebo, on disease-specific quality of life in pediatric patients with celiac disease.
Quality of life will be assessed using the Coeliac Disease Dutch Questionnaire (CDDUX).
Scores will be transformed to a standardized 0-100 scale, with higher scores indicating better quality of life.
Changes from baseline to each follow-up time point will be analyzed and compared between treatment groups.
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From enrollment to the end of the treatment at 6 months
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Changes from baseline in generic health-related quality of life measured by Pediatric Quality of Life Inventory (PedsQL™ 4.0)
Prazo: From enrollment to the end of treatment (6 months)
|
To evaluate the effect of oral supplementation with Sucrosomial® iron, as an add-on to a gluten-free diet (GFD), compared with placebo, on generic health-related quality of life in pediatric patients.
Quality of life will be assessed using the Pediatric Quality of Life Inventory (PedsQL™ 4.0).
Scores will be transformed to a standardized 0-100 scale, with higher scores indicating better quality of life.
Changes from baseline to each follow-up time point will be analyzed and compared between treatment groups.
|
From enrollment to the end of treatment (6 months)
|
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Adherence to GFD
Prazo: From enrollment to the end of the treatment at 6 months
|
To evaluate the adherence to the GFD in patients without Sucrosomial® iron supplementation compared to placebo group. The adherence to GFD and to treatment will be assessed with interview during visits and with dietary diary. |
From enrollment to the end of the treatment at 6 months
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|
Changes from baseline in gastrointestinal symptoms assessed with PedsQL™ 3.0 Gastrointestinal Symptoms Module score
Prazo: From enrollment to the end of the treatment at 6 months
|
To evaluate the modifications from baseline to each follow-up time point in the PedsQL™ 3.0 Gastrointestinal Symptoms Module score, and to compare the two treatment groups. The PedsQL™ 3.0 Gastrointestinal Symptoms Module is a disease-specific instrument designed to evaluate gastrointestinal symptoms in pediatric patients. It is scored on a 0-100 scale, with higher scores indicating fewer gastrointestinal symptoms. |
From enrollment to the end of the treatment at 6 months
|
|
Number and proportion of participants with treatment-related adverse events, graded according to CTCAE v5.0, during Sucrosomial® iron supplementation
Prazo: From enrollment to the end of the treatment at 6 months
|
To evaluate the safety of Sucrosomial® iron supplementation in pediatric patients with hypoferritinemia and/or iron deficiency anemia at the onset of celiac disease.
Adverse events will be collected throughout the study period and classified by type, severity (graded according to CTCAE v5.0 criteria), and relationship to the treatment.
Gastrointestinal adverse events (e.g., abdominal pain, diarrhea, constipation, nausea) will be specifically recorded.
Data will be summarized as the number and proportion of participants experiencing: (1) any adverse event, (2) treatment-related adverse events, and (3) gastrointestinal adverse events.
Serious adverse events will be reported separately.
|
From enrollment to the end of the treatment at 6 months
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Changes from baseline in inflammatory biomarkers
Prazo: From enrollment to the end of the treatment at 6 months
|
Exploratory objectives and endpoints. To evaluate the effects of oral supplementation with Sucrosomial® iron as an add-on to the GFD in pediatric patients with hypoferritinemia and/or iron deficiency anemia at the onset of celiac disease on inflammatory biomarkers. The inflammatory biomarkers (IL-6, IL-10, alpha TNF, serum zonulin) will be assessed from baseline to each time point, in the two treatment groups. |
From enrollment to the end of the treatment at 6 months
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Publicações e links úteis
Publicações Gerais
- 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.
- 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.
- 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.
- 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.
- Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C. The Oslo definitions for coeliac disease and related terms. Gut. 2013 Jan;62(1):43-52. doi: 10.1136/gutjnl-2011-301346. Epub 2012 Feb 16.
- 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.
- Montoro-Huguet MA, Santolaria-Piedrafita S, Canamares-Orbis P, Garcia-Erce JA. Iron Deficiency in Celiac Disease: Prevalence, Health Impact, and Clinical Management. Nutrients. 2021 Sep 28;13(10):3437. doi: 10.3390/nu13103437.
- Ministero della Salute "Linee di indirizzo sugli studi condotti per valutare la sicurezza e le proprietà di prodotti alimentari" - Revisione novembre 2018.
- Corazza GR, Villanacci V. Coeliac disease. J Clin Pathol. 2005 Jun;58(6):573-4. doi: 10.1136/jcp.2004.023978. No abstract available.
- 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.
- Elli L, Ferretti F, Branchi F, Tomba C, Lombardo V, Scricciolo A, Doneda L, Roncoroni L. Sucrosomial Iron Supplementation in Anemic Patients with Celiac Disease Not Tolerating Oral Ferrous Sulfate: A Prospective Study. Nutrients. 2018 Mar 9;10(3):330. doi: 10.3390/nu10030330.
- Repo M, Lindfors K, Maki M, Huhtala H, Laurila K, Lahdeaho ML, Saavalainen P, Kaukinen K, Kurppa K. Anemia and Iron Deficiency in Children With Potential Celiac Disease. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):56-62. doi: 10.1097/MPG.0000000000001234.
- Mearin ML, Agardh D, Antunes H, Al-Toma A, Auricchio R, Castillejo G, Catassi C, Ciacci C, Discepolo V, Dolinsek J, Donat E, Gillett P, Guandalini S, Husby Md DMSc S, Koletzko Md S, Koltai T, Korponay-Szabo IR, Kurppa K, Lionetti E, Marild K, Martinez Ojinaga E, Meijer C, Monachesi C, Polanco I, Popp A, Roca M, Rodriguez-Herrera A, Shamir R, Stordal K, Troncone R, Valitutti F, Vreugdenhil A, Wessels M, Whiting P; ESPGHAN Special Interest Group on Celiac Disease. ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. J Pediatr Gastroenterol Nutr. 2022 Sep 1;75(3):369-386. doi: 10.1097/MPG.0000000000003540. Epub 2022 Jun 27.
- Annibale B, Severi C, Chistolini A, Antonelli G, Lahner E, Marcheggiano A, Iannoni C, Monarca B, Delle Fave G. Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients. Am J Gastroenterol. 2001 Jan;96(1):132-7. doi: 10.1111/j.1572-0241.2001.03463.x.
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- Mahadev S, Laszkowska M, Sundstrom J, Bjorkholm M, Lebwohl B, Green PHR, Ludvigsson JF. Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis. Gastroenterology. 2018 Aug;155(2):374-382.e1. doi: 10.1053/j.gastro.2018.04.016. Epub 2018 Apr 22.
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