Probiotic Use in Oral Iron Replacement Deficiency Anemia Patients Initiating Oral Iron Replacement

NCT06521879 | Completed

• 1 other identifier: 2020-265
• Study Type: interventional
• Target: 295
• Locations: 1 country
• Sites: 1

Brief Summary

Investigation of gastrointestinal tolerability, treatment compliance and iron status markers in patients with iron deficiency anemia who received oral iron replacement therapy with versus without concomitant probiotic supplementation

Conditions

Iron Deficiency Anemia Treatment; Iron Deficiency Anemia

Keywords

iron deficiency anemia; oral iron replacement; probiotic supplementation; Lactobacillus plantarum 299v; gastrointestinal tolerability; iron status markers

Outcome Measures

Primary Outcomes (1)

• Gastrointestinal Tolerance and Treatment Compliance in Iron Deficiency Anemia Patients Using Oral Iron with or without Lactobacillus plantarum 299v Probiotic Supplementation

  To investigate gastrointestinal tolerability and treatment compliance in patients with iron deficiency anemia who received oral iron replacement therapy with versus without concomitant Lactobacillus plantarum 299v (L. plantarum 299v) probiotic supplementation. Gastrointestinal intolerance symptoms (loss of appetite, nausea, vomiting, abdominal pain, diarrhea, constipation, and bloating) will be assessed using a structured questionnaire with yes or no questions. Measurement Tool: Structured Questionnaire Data Collection Points: Baseline, within the first 30 days of iron replacement therapy (IRT), and at any time during the 3-month IRT. Scale Description: The questionnaire will include yes or no questions to determine the presence of gastrointestinal intolerance symptoms. A "yes" response indicates the presence of a symptom, and a "no" response indicates its absence.

  3 months

Study Arms (2)

IRT-Only

NO INTERVENTION

Iron deficiency anemia patients receive iron replacement therapy alone.

IRT-Pro

EXPERIMENTAL

Iron deficiency anemia patients receive iron replacement therapy plus L. plantarum 299v probiotic support

Dietary Supplement: Lactobacillus plantarum 299v probiotic support

Interventions

Lactobacillus plantarum 299v probiotic support DIETARY_SUPPLEMENT

Addition of Lactobacillus plantarum 299v (L. plantarum 299v) probiotic supplementation to iron replacement therapy.

IRT-Pro

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment-naïve patients diagnosed with newly diagnosed iron deficiency anemia

You may not qualify if:

• Irritable bowel syndrome
• Celiac disease
• Untreated active menometrorrhagia
• Hemorrhoidal disease
• Previous iron replacement therapy

Sponsors & Collaborators

• Antalya Training and Research Hospital: lead

Study Sites (1)

Antalya Training and Research Hospital

Antalya, 07050, Turkey (Türkiye)

Location

Related Publications (38)

• Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, Pena-Rosas JP, Bhutta ZA, Ezzati M; Nutrition Impact Model Study Group (Anaemia). Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995-2011: a systematic analysis of population-representative data. Lancet Glob Health. 2013 Jul;1(1):e16-25. doi: 10.1016/S2214-109X(13)70001-9. Epub 2013 Jun 25.

  PMID: 25103581 BACKGROUND

• Kumar SB, Arnipalli SR, Mehta P, Carrau S, Ziouzenkova O. Iron Deficiency Anemia: Efficacy and Limitations of Nutritional and Comprehensive Mitigation Strategies. Nutrients. 2022 Jul 20;14(14):2976. doi: 10.3390/nu14142976.

  PMID: 35889932 BACKGROUND

• Seo H, Yoon SY, Ul-Haq A, Jo S, Kim S, Rahim MA, Park HA, Ghorbanian F, Kim MJ, Lee MY, Kim KH, Lee N, Won JH, Song HY. The Effects of Iron Deficiency on the Gut Microbiota in Women of Childbearing Age. Nutrients. 2023 Jan 30;15(3):691. doi: 10.3390/nu15030691.

  PMID: 36771397 BACKGROUND

• Zakrzewska Z, Zawartka A, Schab M, Martyniak A, Skoczen S, Tomasik PJ, Wedrychowicz A. Prebiotics, Probiotics, and Postbiotics in the Prevention and Treatment of Anemia. Microorganisms. 2022 Jun 30;10(7):1330. doi: 10.3390/microorganisms10071330.

  PMID: 35889049 BACKGROUND

• Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010 Dec 2;116(23):4754-61. doi: 10.1182/blood-2010-05-286260. Epub 2010 Sep 8.

  PMID: 20826717 BACKGROUND

• Vonderheid SC, Tussing-Humphreys L, Park C, Pauls H, OjiNjideka Hemphill N, LaBomascus B, McLeod A, Koenig MD. A Systematic Review and Meta-Analysis on the Effects of Probiotic Species on Iron Absorption and Iron Status. Nutrients. 2019 Dec 3;11(12):2938. doi: 10.3390/nu11122938.

  PMID: 31816981 BACKGROUND

• Korcok DJ, Trsic-Milanovic NA, Ivanovic ND, Dordevic BI. Development of Probiotic Formulation for the Treatment of Iron Deficiency Anemia. Chem Pharm Bull (Tokyo). 2018 Apr 1;66(4):347-352. doi: 10.1248/cpb.c17-00634. Epub 2018 Jan 19.

  PMID: 29353864 BACKGROUND

• Rusu IG, Suharoschi R, Vodnar DC, Pop CR, Socaci SA, Vulturar R, Istrati M, Morosan I, Farcas AC, Kerezsi AD, Muresan CI, Pop OL. Iron Supplementation Influence on the Gut Microbiota and Probiotic Intake Effect in Iron Deficiency-A Literature-Based Review. Nutrients. 2020 Jul 4;12(7):1993. doi: 10.3390/nu12071993.

  PMID: 32635533 BACKGROUND

• Bazeley JW, Wish JB. Recent and Emerging Therapies for Iron Deficiency in Anemia of CKD: A Review. Am J Kidney Dis. 2022 Jun;79(6):868-876. doi: 10.1053/j.ajkd.2021.09.017. Epub 2021 Nov 7.

  PMID: 34758368 BACKGROUND

• Kumar A, Sharma E, Marley A, Samaan MA, Brookes MJ. Iron deficiency anaemia: pathophysiology, assessment, practical management. BMJ Open Gastroenterol. 2022 Jan;9(1):e000759. doi: 10.1136/bmjgast-2021-000759.

  PMID: 34996762 BACKGROUND

• Gomez-Ramirez S, Brilli E, Tarantino G, Munoz M. Sucrosomial(R) Iron: A New Generation Iron for Improving Oral Supplementation. Pharmaceuticals (Basel). 2018 Oct 4;11(4):97. doi: 10.3390/ph11040097.

  PMID: 30287781 BACKGROUND

• Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol. 2016 Jan;91(1):31-8. doi: 10.1002/ajh.24201. Epub 2015 Nov 17.

  PMID: 26408108 BACKGROUND

• Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015 Feb 20;10(2):e0117383. doi: 10.1371/journal.pone.0117383. eCollection 2015.

  PMID: 25700159 BACKGROUND

• Deschemin JC, Noordine ML, Remot A, Willemetz A, Afif C, Canonne-Hergaux F, Langella P, Karim Z, Vaulont S, Thomas M, Nicolas G. The microbiota shifts the iron sensing of intestinal cells. FASEB J. 2016 Jan;30(1):252-61. doi: 10.1096/fj.15-276840. Epub 2015 Sep 14.

  PMID: 26370847 BACKGROUND

• Jaeggi T, Kortman GA, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, Njenga J, Mwangi A, Kvalsvig J, Lacroix C, Zimmermann MB. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut. 2015 May;64(5):731-42. doi: 10.1136/gutjnl-2014-307720. Epub 2014 Aug 20.

  PMID: 25143342 BACKGROUND

• Hoppe M, Onning G, Berggren A, Hulthen L. Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age. Br J Nutr. 2015 Oct 28;114(8):1195-202. doi: 10.1017/S000711451500241X.

  PMID: 26428277 BACKGROUND

• Wells JM. Immunomodulatory mechanisms of lactobacilli. Microb Cell Fact. 2011 Aug 30;10 Suppl 1(Suppl 1):S17. doi: 10.1186/1475-2859-10-S1-S17. Epub 2011 Aug 30.

  PMID: 21995674 BACKGROUND

• Goossens D, Jonkers D, Russel M, Thijs A, van den Bogaard A, Stobberingh E, Stockbrugger R. Survival of the probiotic, L. plantarum 299v and its effects on the faecal bacterial flora, with and without gastric acid inhibition. Dig Liver Dis. 2005 Jan;37(1):44-50. doi: 10.1016/j.dld.2004.07.018.

  PMID: 15702859 BACKGROUND

• Ducrotte P, Sawant P, Jayanthi V. Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol. 2012 Aug 14;18(30):4012-8. doi: 10.3748/wjg.v18.i30.4012.

  PMID: 22912552 BACKGROUND

• Niedzielin K, Kordecki H, Birkenfeld B. A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2001 Oct;13(10):1143-7. doi: 10.1097/00042737-200110000-00004.

  PMID: 11711768 BACKGROUND

• Bering S, Sjoltov L, Wrisberg SS, Berggren A, Alenfall J, Jensen M, Hojgaard L, Tetens I, Bukhave K. Viable, lyophilized lactobacilli do not increase iron absorption from a lactic acid-fermented meal in healthy young women, and no iron absorption occurs in the distal intestine. Br J Nutr. 2007 Nov;98(5):991-7. doi: 10.1017/S0007114507761809. Epub 2007 Sep 3.

  PMID: 17764597 BACKGROUND

• Scheers N, Rossander-Hulthen L, Torsdottir I, Sandberg AS. Increased iron bioavailability from lactic-fermented vegetables is likely an effect of promoting the formation of ferric iron (Fe(3+)). Eur J Nutr. 2016 Feb;55(1):373-82. doi: 10.1007/s00394-015-0857-6. Epub 2015 Feb 12.

  PMID: 25672527 BACKGROUND

• Sahin K, Sahinturk Y, Koker G, Ozcelik Koker G, Bostan F, Kok M, Uyar S, Cekin AH. Metformin with Versus without Concomitant Probiotic Therapy in Newly Diagnosed Patients with Type 2 Diabetes or Prediabetes: A Comparative Analysis in Relation to Glycemic Control, Gastrointestinal Side Effects, and Treatment Compliance. Turk J Gastroenterol. 2022 Nov;33(11):925-933. doi: 10.5152/tjg.2022.211063.

  PMID: 36098362 BACKGROUND

• Cekin AH, Sahinturk Y, Akbay Harmandar F, Uyar S, Yolcular BO, Cekin Y. Use of probiotics as an adjuvant to sequential H. pylori eradication therapy: impact on eradication rates, treatment resistance, treatment-related side effects, and patient compliance. Turk J Gastroenterol. 2017 Jan;28(1):3-11. doi: 10.5152/tjg.2016.0278. Epub 2016 Dec 23.

  PMID: 28007678 BACKGROUND

• Endo H, Higurashi T, Hosono K, Sakai E, Sekino Y, Iida H, Sakamoto Y, Koide T, Takahashi H, Yoneda M, Tokoro C, Inamori M, Abe Y, Nakajima A. Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled study. J Gastroenterol. 2011 Jul;46(7):894-905. doi: 10.1007/s00535-011-0410-1. Epub 2011 May 10.

  PMID: 21556830 BACKGROUND

• Axling U, Onning G, Martinsson Niskanen T, Larsson N, Hansson SR, Hulthen L. The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial. Acta Obstet Gynecol Scand. 2021 Sep;100(9):1602-1610. doi: 10.1111/aogs.14153. Epub 2021 Apr 21.

  PMID: 33880752 BACKGROUND

• OjiNjideka Hemphill N, Pezley L, Steffen A, Elam G, Kominiarek MA, Odoms-Young A, Kessee N, Hamm A, Tussing-Humphreys L, Koenig MD. Feasibility Study of Lactobacillus Plantarum 299v Probiotic Supplementation in an Urban Academic Facility among Diverse Pregnant Individuals. Nutrients. 2023 Feb 9;15(4):875. doi: 10.3390/nu15040875.

  PMID: 36839232 BACKGROUND

• Sandberg AS, Onning G, Engstrom N, Scheers N. Iron Supplements Containing Lactobacillus plantarum 299v Increase Ferric Iron and Up-regulate the Ferric Reductase DCYTB in Human Caco-2/HT29 MTX Co-Cultures. Nutrients. 2018 Dec 8;10(12):1949. doi: 10.3390/nu10121949.

  PMID: 30544799 BACKGROUND

• Jaramillo A, Briones L, Andrews M, Arredondo M, Olivares M, Brito A, Pizarro F. Effect of phytic acid, tannic acid and pectin on fasting iron bioavailability both in the presence and absence of calcium. J Trace Elem Med Biol. 2015 Apr;30:112-7. doi: 10.1016/j.jtemb.2014.11.005. Epub 2014 Nov 27.

  PMID: 25544113 BACKGROUND

• Liu H, Wu W, Luo Y. Oral and intravenous iron treatment alter the gut microbiome differentially in dialysis patients. Int Urol Nephrol. 2023 Mar;55(3):759-767. doi: 10.1007/s11255-022-03377-0. Epub 2022 Sep 27.

  PMID: 36166104 BACKGROUND

• Kujawa-Szewieczek A, Adamczak M, Kwiecien K, Dudzicz S, Gazda M, Wiecek A. The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics. Nutrients. 2015 Dec 4;7(12):10179-88. doi: 10.3390/nu7125526.

  PMID: 26690209 BACKGROUND

• Kazmierczak-Siedlecka K, Daca A, Folwarski M, Witkowski JM, Bryl E, Makarewicz W. The role of Lactobacillus plantarum 299v in supporting treatment of selected diseases. Cent Eur J Immunol. 2020;45(4):488-493. doi: 10.5114/ceji.2020.101515. Epub 2021 Jan 25.

  PMID: 33613097 BACKGROUND

• Serati M, Torella M. Preventing complications by persistence with iron replacement therapy: a comprehensive literature review. Curr Med Res Opin. 2019 Jun;35(6):1065-1072. doi: 10.1080/03007995.2018.1552850. Epub 2019 Jan 3.

  PMID: 30477352 BACKGROUND

• Richards T, Breymann C, Brookes MJ, Lindgren S, Macdougall IC, McMahon LP, Munro MG, Nemeth E, Rosano GMC, Schiefke I, Weiss G. Questions and answers on iron deficiency treatment selection and the use of intravenous iron in routine clinical practice. Ann Med. 2021 Dec;53(1):274-285. doi: 10.1080/07853890.2020.1867323.

  PMID: 33426933 BACKGROUND

• Bering S, Suchdev S, Sjoltov L, Berggren A, Tetens I, Bukhave K. A lactic acid-fermented oat gruel increases non-haem iron absorption from a phytate-rich meal in healthy women of childbearing age. Br J Nutr. 2006 Jul;96(1):80-5. doi: 10.1079/bjn20061683.

  PMID: 16869994 BACKGROUND

• Axling U, Onning G, Combs MA, Bogale A, Hogstrom M, Svensson M. The Effect of Lactobacillus plantarum 299v on Iron Status and Physical Performance in Female Iron-Deficient Athletes: A Randomized Controlled Trial. Nutrients. 2020 Apr 30;12(5):1279. doi: 10.3390/nu12051279.

  PMID: 32365981 BACKGROUND

• Fikri B, Ridha NR, Putri SH, Salekede SB, Juliaty A, Tanjung C, Massi N. Effects of probiotics on immunity and iron homeostasis: A mini-review. Clin Nutr ESPEN. 2022 Jun;49:24-27. doi: 10.1016/j.clnesp.2022.03.031. Epub 2022 Mar 31.

  PMID: 35623819 BACKGROUND

• Koker G, Sahinturk Y, Ozcelik Koker G, Coskuner MA, Eren Durmus M, Catli MM, Cekin AH. Improved gastrointestinal tolerance and iron status via probiotic use in iron deficiency anaemia patients initiating oral iron replacement: a randomised controlled trial. Br J Nutr. 2024 Nov 28;132(10):1308-1316. doi: 10.1017/S0007114524002757. Epub 2024 Nov 4.

  PMID: 39494607 DERIVED

MeSH Terms

Conditions

Anemia, Iron-Deficiency

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Gokhan Koker, MD

  Antalya Training and Research Hospital

  PRINCIPAL INVESTIGATOR

• Yasin Sahinturk, MD

  Antalya Training and Research Hospital

  STUDY CHAIR

• Gulhan Ozcelik Koker, MD

  Antalya Training and Research Hospital

  STUDY CHAIR

• Ali Coskuner, MD

  Antalya Training and Research Hospital

  STUDY CHAIR

• Merve Eren Durmuş, MD

  Antalya Training and Research Hospital

  STUDY CHAIR

• Mutlu M Catli, MD

  Antalya Training and Research Hospital

  STUDY CHAIR

• Ayhan H Cekin, MD

  Antalya Training and Research Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Patients were randomly assigned via simple randomization method (computer- generated random number sequence)

Study Record Dates

• First Submitted: July 14, 2024
• First Posted: July 26, 2024
• Study Start: September 1, 2022
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: July 26, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)