Risk of Anemia and Effects of Oral Iron Therapy in Non-Anemic Iron-Deficient Women (18-55 Years)

NCT07263529 | Recruiting

• 3 other identifiers: 2024-KAEK-22E-14028348-302.14.02-985103E-15916306-604.01-281470566
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the risk of anemia development in women aged 18-55 years with non-anemic iron deficiency and evaluates the clinical effects of oral iron therapy. The study consists of a two-month nutritional intervention phase followed by a one-month oral iron treatment phase. Participants first receive dietary counseling aimed at increasing iron intake and absorption. After two months, changes in hematologic parameters and symptoms are evaluated. Women with persistent iron deficiency then receive daily oral ferrous sulfate (80 mg elemental iron) for one month. The study aims to identify early predictors of anemia progression and to assess the impact of dietary modification and oral iron therapy on symptoms and laboratory findings.

Conditions

Non-Anemic Iron Deficiency

Keywords

Iron deficiency without anemia; Risk of anemia; Clinical effects of oral iron therapy; Women 18-55; Ferritin; Hemoglobin; Symptom scores; Nutritional intervention; Iron supplementation

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Patient-Reported Iron Deficiency Symptom Scores After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy

  Change in patient-reported symptoms including fatigue, weakness, dizziness, and cognitive function etc. measured at baseline, after 2-month nutritional intervention, and after 1-month oral iron therapy.

  Baseline, Week 8 (post-nutritional intervention), Week 12 (post-oral iron therapy)

Secondary Outcomes (5)

• Change from Baseline in Hemoglobin and Red Blood Cell Indices After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy

  Baseline, Week 8, Week 12

• Change from Baseline in Serum Iron and Total Iron Binding Capacity After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy

  Baseline, Week 8, Week 12

• Incidence of Progression to Anemia After 2-Month Nutritional Intervention

  Baseline to Week 8

• Proportion of Participants Demonstrating Hematologic Response to 1-Month Oral Iron Therapy (Hb increase ≥1.0 g/dL)

  Week 8 to Week 12

• Proportion of Participants Demonstrating Ferritin Response to 1-Month Oral Iron Therapy (Ferritin increase ≥15 µg/L or ≥30 µg/L absolute)

  Week 8 to Week 12

Other Outcomes (3)

• Adherence to Nutritional Intervention Over 2 Months

  Week 0 to Week 8

• Adherence to Oral Iron Therapy Over 1 Month

  Week 8 to Week 12

• Incidence of Treatment-Related Adverse Events During 1-Month Oral Iron Therapy

  Week 8 to Week 12

Study Arms (1)

ARM 1 - Nutritional Intervention with Post-Intervention Subgrouping

EXPERIMENTAL

All participants (N=60) begin with isolated non-anemic iron deficiency and receive a 2-month standardized nutritional intervention to improve iron intake and absorption. Afterward, participants are stratified into five subgroups (ARM1-0 to ARM1-4) based on hematologic response. Subgroups ARM1-1 to ARM1-4 represent persistent deficiency (ferritin \<15 µg/L with normal CRP) and will receive oral elemental iron. * ARM1-0: Normalized or maintained iron status (no deficiency) - no iron therapy administered. * ARM1-1: Persistent isolated iron deficiency - receives oral elemental iron. * ARM1-2: Minimal hemoglobin decline (\<1 g/dL) with microcytosis/hypochromia - receives oral elemental iron. * ARM1-3: Hemoglobin decline \>1 g/dL but above anemia threshold, with microcytosis/hypochromia - receives oral elemental iron. * ARM1-4: Overt iron deficiency anemia - receives oral elemental iron.

Other: Dietary Intervention (2 months); Drug: Oral Elemental Iron (Ferrous Sulfate) 80 mg/day

Interventions

Dietary Intervention (2 months) OTHER

A two-month nutritional counseling program for all participants (N = 60) with isolated non-anemic iron deficiency. The program emphasized the inclusion of iron-rich foods (both heme and non-heme sources), the use of enhancers of iron absorption (such as vitamin C), and practical strategies to reduce absorption inhibitors (e.g., limiting tea and coffee consumption around meals, reviewing antacid use). Participants received biweekly phone follow-ups to monitor adherence and assess symptoms.

Also known as: Nutritional Intervention (2 months)

ARM 1 - Nutritional Intervention with Post-Intervention Subgrouping

Oral Elemental Iron (Ferrous Sulfate) 80 mg/day DRUG

One-month oral therapy with 80 mg elemental iron (ferrous sulfate) daily for participants with persistent iron deficiency after the nutritional phase (ferritin \< 15 µg/L). Biweekly phone follow-up for adherence and symptom checks. Adherence and side effects monitored at clinic visit or by phone.

Also known as: Oral Iron Intervention (1 month)

ARM 1 - Nutritional Intervention with Post-Intervention Subgrouping

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female participants aged 18-55 years (including premenopausal and menopausal women).
• Normal hemoglobin level (≥ 12 g/dL).
• Serum ferritin \< 15 μg/L (WHO criteria for iron deficiency).
• Mentzer index \> 13.
• Normal levels of vitamin B12, folic acid, thyroid hormones (TSH and sT4), and C-reactive protein (CRP \< 5 mg/L).
• Non-anemic iron deficiency confirmed by laboratory results.
• Good general health and cognitive capacity to provide informed consent.
• Willingness to participate, comply with study procedures, and provide written informed consent.

You may not qualify if:

• Pregnancy or postpartum period.
• Acute or chronic infections.
• History or suspicion of malignancy.
• Chronic inflammatory or autoimmune diseases.
• Chronic fatigue syndrome or depressive disorders.
• Chronic kidney disease or renal failure (acute or chronic).
• Congestive heart failure, ischemic heart disease, or cerebrovascular disease.
• Coagulopathy or clinically significant bleeding tendency.
• Hematological disorders (e.g., thalassemia, hemoglobinopathies).
• Postoperative patients, transplant recipients, or dialysis patients.
• Currently using any form of iron supplementation or treatment.
• Any condition that, in the investigator's opinion, may interfere with the participant's safety or the interpretation of study results.

Sponsors & Collaborators

• Istanbul University - Cerrahpasa: lead

Study Sites (1)

Kagıthane No. 5 Family Health Center

Kâğıthane, Istanbul, 34413, Turkey (Türkiye)

RECRUITING

Related Publications (17)

• Ortancil O, Sanli A, Eryuksel R, Basaran A, Ankarali H. Association between serum ferritin level and fibromyalgia syndrome. Eur J Clin Nutr. 2010 Mar;64(3):308-12. doi: 10.1038/ejcn.2009.149. Epub 2010 Jan 20.

  PMID: 20087382 BACKGROUND

• Skolmowska D, Glabska D, Kolota A, Guzek D. Effectiveness of Dietary Interventions to Treat Iron-Deficiency Anemia in Women: A Systematic Review of Randomized Controlled Trials. Nutrients. 2022 Jun 30;14(13):2724. doi: 10.3390/nu14132724.

  PMID: 35807904 BACKGROUND

• Silva Neto LGR, Santos Neto JED, Bueno NB, de Oliveira SL, Ataide TDR. Effects of iron supplementation versus dietary iron on the nutritional iron status: Systematic review with meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2019;59(16):2553-2561. doi: 10.1080/10408398.2018.1459469. Epub 2018 Apr 30.

  PMID: 29611716 RESULT

• Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, Melse-Boonstra A, Brittenham G, Swinkels DW, Zimmermann MB. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015 Oct 22;126(17):1981-9. doi: 10.1182/blood-2015-05-642223. Epub 2015 Aug 19.

  PMID: 26289639 RESULT

• Stefan MW, Gundermann DM, Sharp MH, Jennings BA, Gheith RH, Lowery RP, LowDog T, Ghatak SB, Barbosa J, Wilson JM. Assessment of the Efficacy of a Low-Dose Iron Supplement in Restoring Iron Levels to Normal Range among Healthy Premenopausal Women with Iron Deficiency without Anemia. Nutrients. 2023 Jun 3;15(11):2620. doi: 10.3390/nu15112620.

  PMID: 37299583 RESULT

• Nemeth E, Ganz T. Hepcidin and Iron in Health and Disease. Annu Rev Med. 2023 Jan 27;74:261-277. doi: 10.1146/annurev-med-043021-032816. Epub 2022 Jul 29.

  PMID: 35905974 RESULT

• Zhu XY, Wu TT, Wang HM, Li X, Ni LY, Chen TJ, Qiu MY, Shen J, Liu T, Ondo WG, Wu YC. Correlates of Nonanemic Iron Deficiency in Restless Legs Syndrome. Front Neurol. 2020 Apr 30;11:298. doi: 10.3389/fneur.2020.00298. eCollection 2020.

  PMID: 32425874 RESULT

• Sawada T, Konomi A, Yokoi K. Iron deficiency without anemia is associated with anger and fatigue in young Japanese women. Biol Trace Elem Res. 2014 Jun;159(1-3):22-31. doi: 10.1007/s12011-014-9963-1. Epub 2014 Apr 23.

  PMID: 24756645 RESULT

• da Silva Lopes K, Yamaji N, Rahman MO, Suto M, Takemoto Y, Garcia-Casal MN, Ota E. Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of systematic reviews. Cochrane Database Syst Rev. 2021 Sep 26;9(9):CD013092. doi: 10.1002/14651858.CD013092.pub2.

  PMID: 34564844 RESULT

• Miles LF, Litton E, Imberger G, Story D. Intravenous iron therapy for non-anaemic, iron-deficient adults. Cochrane Database Syst Rev. 2019 Dec 20;12(12):CD013084. doi: 10.1002/14651858.CD013084.pub2.

  PMID: 31860749 RESULT

• Houston BL, Hurrie D, Graham J, Perija B, Rimmer E, Rabbani R, Bernstein CN, Turgeon AF, Fergusson DA, Houston DS, Abou-Setta AM, Zarychanski R. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials. BMJ Open. 2018 Apr 5;8(4):e019240. doi: 10.1136/bmjopen-2017-019240.

  PMID: 29626044 RESULT

• Fletcher A, Forbes A, Svenson N, Wayne Thomas D; A British Society for Haematology Good Practice Paper. Guideline for the laboratory diagnosis of iron deficiency in adults (excluding pregnancy) and children. Br J Haematol. 2022 Feb;196(3):523-529. doi: 10.1111/bjh.17900. Epub 2021 Oct 24. No abstract available.

  PMID: 34693519 RESULT

• Clenin GE. The treatment of iron deficiency without anaemia (in otherwise healthy persons). Swiss Med Wkly. 2017 Jun 14;147:w14434. doi: 10.4414/smw.2017.14434. eCollection 2017.

  PMID: 28634965 RESULT

• WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations [Internet]. Geneva: World Health Organization; 2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK569880/

  PMID: 33909381 RESULT

• Balendran S, Forsyth C. Non-anaemic iron deficiency. Aust Prescr. 2021 Dec;44(6):193-196. doi: 10.18773/austprescr.2021.052. Epub 2021 Dec 1.

  PMID: 35002031 RESULT

• Guideline on haemoglobin cutoffs to define anaemia in individuals and populations [Internet]. Geneva: World Health Organization; 2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK602198/

  PMID: 38530913 RESULT

• Soppi ET. Iron deficiency without anemia - a clinical challenge. Clin Case Rep. 2018 Apr 17;6(6):1082-1086. doi: 10.1002/ccr3.1529. eCollection 2018 Jun.

  PMID: 29881569 RESULT

Related Links

• Ethical approval: Istanbul University-Cerrahpasa Clinical Research Ethics Committee.
• Study site: Kagithane 5 No'lu Family Health Center (ASM), conducted by Dr. Osman Demir.
• Institutional authorization: Permission for study implementation obtained from Istanbul Provincial Health Directorate.

MeSH Terms

Conditions

Iron Deficiencies

Interventions

Diet Therapy; ferrous sulfate

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nutrition Therapy; Therapeutics

Study Officials

• Osman Demir, MD

  Kağıthane No.5 Family Health Center, Istanbul, Turkey

  PRINCIPAL INVESTIGATOR

• Ayşen Fenercioğlu, Assoc Prof

  Istanbul University - Cerrahpaşa, Cerrahpaşa Faculty of Medicine

  STUDY DIRECTOR

Central Study Contacts

Osman Demir, MD

CONTACT

+90 532 291 4470; osman.demir@iuc.edu.tr

Ayşen Fenercioğlu, Assoc Prof

CONTACT

+90 537 964 5751; aysen.fenercioglu@iuc.edu.tr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: No parties are masked; this is an open-label study.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: All participants initially receive the same nutritional intervention; after post-intervention evaluation, subgroups are defined and those with persistent iron deficiency receive the drug intervention.

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: December 4, 2025
• Study Start: September 1, 2025
• Primary Completion: January 1, 2026
• Study Completion: February 28, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)