Risk of Anemia Development and Clinical Effects of Oral Iron Therapy in Women (18-55 Years) With Non-Anemic Iron Deficiency
Phase: NA
Conditions: Non-Anemic Iron Deficiency
Sponsor: Istanbul University - Cerrahpasa

Document 1 — Study Protocol (NAID-F)
Cover Page - Official Study Title: Risk of Anemia Development and Clinical Effects of Oral Iron Therapy in
Women (18–55 Years) With Non-Anemic Iron Deficiency - NCT Number: [To be assigned] - Document
Date: October 28, 2025
1. Study Identification - Organization's Unique Protocol ID: 2024-KAEK-22 - Brief Title: Risk of Anemia
and Effects of Oral Iron Therapy in Non-Anemic Iron-Deficient Women (18–55 Years) - Acronym: NAID-F -
Study Type: Interventional - Official Title: Risk of Anemia Development and Clinical Effects of Oral Iron
Therapy in Women (18–55 Years) With Non-Anemic Iron Deficiency - Secondary IDs: - Other Identifier:
E-14028348-302.14.02-985103 (Istanbul Univ.–Cerrahpasa Faculty of Medicine, Thesis Approval) - Other
Identifier: E-15916306-604.01-281470566 (Istanbul Provincial Health Directorate, Institutional Approval)
2. Study Status - Record Verification Date: October 2025 - Overall Recruitment Status: Recruiting - Study
Start Date: September 01, 2025 (Actual) - Primary Completion Date: January 01, 2026 (Anticipated) -
Study Completion Date: February 28, 2026 (Anticipated)
3.  Sponsors  and  Collaborators -  Responsible  Party:  Principal  Investigator  -  Investigator  Name
[Username]:  Osman  Demir,  MD  [odemir]  -  Investigator  Official  Title:  MD  -  Investigator  Affiliation:
Istanbul University - Cerrahpasa - Name of Sponsor: Istanbul University - Cerrahpasa - Collaborators:
Istanbul University - Cerrahpasa
4. Oversight - U.S. FDA-Regulated Drug: No - U.S. FDA-Regulated Device: No - IND/IDE: No - Human
Subjects Protection Review: Approved - Board Name: Istanbul University – Cerrahpaşa Clinical Research
Ethics  Committee  -  Approval  Number:  2024-KAEK-22  -  Board  Affiliation:  Istanbul  University  –
Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Clinical Research Ethics Committee - Board Contact: +90
(212) 414 32 52, kliniketik@iuc.edu.tr
5. Study Description - Brief Summary: This study investigates anemia risk and clinical effects of oral
iron therapy in women aged 18–55 years with non-anemic iron deficiency. Conducted in two phases at
Kağıthane 5 No’lu Family Health Center, Istanbul. - Phase 1 (Observational Nutrition Intervention, 2
months): All participants receive dietary guidance to improve iron intake and absorption. Biweekly
phone  monitoring.  Participants  classified  into  five  subgroups  (ARM1-0  to  ARM1-4)  based  on
hematologic  outcomes  after  2  months.  -  Phase  2  (Experimental  Oral  Iron  Therapy,  1  month):
Participants in ARM1-1 to ARM1-4 receive oral ferrous sulfate 80 mg/day. ARM1-0 participants maintain
normal iron status and do not receive therapy.
6. Conditions - Non-Anemic Iron Deficiency - Risk of Anemia Development - Clinical Effects of Oral Iron
Therapy  -  Keywords:  Iron  Deficiency  Without  Anemia,  Women  18–55  years,  Hemoglobin,  Ferritin,
Symptom Scores, Prospective Cohort, Experimental Intervention, Iron Supplementation, Nutritional
Intervention, Study Design
7. Study Design - Primary Purpose: Treatment - Study Phase: N/A - Interventional Study Model: Single
Group Assignment - Number of Arms: 1 - Masking: None (Open Label) - Allocation: Non-Randomized -
Enrollment: 60 (Anticipated) - Arms and Interventions: - Experimental: ARM 1 – Nutritional Intervention
with Post-Intervention Subgrouping (All participants receive 2-month dietary intervention; subgrouping
based on lab outcomes; persistent iron deficiency participants receive 1-month oral elemental iron 80
1

mg/day). - Other: Dietary Intervention (2 months) – iron-rich foods, absorption enhancement strategies,
biweekly follow-up. - Drug: Oral Elemental Iron (Ferrous Sulfate) 80 mg/day – 1 month for persistent
iron deficiency.
8.  Outcome  Measures -  Primary  Outcome: 1.  Change  from  Baseline  in  Patient-Reported  Iron
Deficiency Symptom Scores (Baseline, Week 8, Week 12) - Secondary Outcomes: 2. Hemoglobin and
RBC indices (Baseline, Week 8, Week 12) 3. Serum Iron and TIBC (Baseline, Week 8, Week 12) 4.
Incidence of progression to anemia after 2-month nutritional intervention (Week 8) 5. Hematologic
response to 1-month oral iron therapy (Hb increase ≥1 g/dL; Week 8–12) 6. Ferritin response to 1-
month  oral  iron  therapy  (Week  8–12)  -  Pre-specified  Outcomes: 7.  Adherence  to  Nutritional
Intervention (Week 0–8) 8. Adherence to Oral Iron Therapy (Week 8–12) 9. Incidence of Treatment-
Related Adverse Events (Week 8–12)
9. Statistical Analysis Plan - Data will be analyzed using repeated measures ANOVA for longitudinal
comparisons  of  laboratory  values  and  symptom  scores.  -  Participants  will  be  stratified  into  five
subgroups (ARM1-0 to ARM1-4) based on hematologic outcomes after 2 months. - ANOVA comparisons
will be performed across these five groups to assess differences in outcomes including hemoglobin,
ferritin, RBC indices, serum iron, TIBC, and patient-reported symptom scores. - Within-group changes
over time will be analyzed using paired t-tests. - Categorical data (proportions and percentages) will be
analyzed using Chi-Square tests. - Continuous variables will be summarized as mean ± SD; categorical
variables as counts and percentages. - Subgroup analyses will focus on ARM1-1 to ARM1-4 participants
who receive oral iron therapy. - Sample size of 60 determined via G*Power analysis (α=0.05, 80% power).
- Missing data handled via multiple imputation if >5% missing.
10. Eligibility - Accepts Healthy Volunteers: No - Sex: Female - Age Limits: 18–55 years - Inclusion
Criteria: Female, 18–55 years, non-anemic iron deficiency (ferritin <15 μg/L), normal Hb, B12, folate,
TSH,  sT4,  CRP  <5  mg/L,  informed  consent.  -  Exclusion  Criteria:  Pregnancy/postpartum,  infection,
malignancy, chronic disease, depression, chronic fatigue, kidney/heart disease, hematologic disorders,
ongoing iron therapy.
11.  Contacts  and  Locations -  Central  Contact  Person:  Osman  Demir  (+90  532  291  4470,
osman.demir@iuc.edu.tr)  -  Central  Contact  Backup:  Ayşen  Fenercioğlu  (+90  537  964  5751,
aysen.fenercioglu@iuc.edu.tr) - Study Officials: Osman Demir (Principal Investigator), Kağıthane No.5
Family  Health  Center,  Istanbul,  Turkey;  Ayşen  Fenercioğlu  (Study  Director),  Istanbul  University  –
Cerrahpaşa. - Location: Kağıthane No.5 Family Health Center, Istanbul, Turkey (Recruiting)
12. IPD Sharing Statement - Plan to Share IPD: Undecided; to be determined post-study in accordance
with ethics and participant privacy.
13. References and Additional Information 1. World Health Organization. Guideline on the Use of
Ferritin Concentrations to Assess Iron Status in Individuals and Populations. Geneva: WHO; 2020. 2.
Soppi ET. Iron deficiency without anemia: a clinical challenge. Clin Case Rep. 2018;6:1082–1086. https://
doi.org/10.1002/ccr3.1529 3.  Balendran  S,  Forsyth  C.  Non-anaemic  iron  deficiency.  Aust  Prescr.
2021;44(6):193–196. doi:10.18773/austprescr.2021.052 4. World Health Organization & FAO. Guidelines
on Food Fortification with Micronutrients. Geneva: WHO Press; 2006. 5. Skolmowska D, Glabska D,
Kolota A, Guzek D. Effectiveness of dietary interventions to treat iron-deficiency anemia in women: a
systematic review. Nutrients. 2022;14:2724. https://doi.org/10.3390/nu14132724 6. Clenin G. Treatment
of  iron  deficiency  without  anaemia.  Swiss  Med  Wkly.  2017;147:w14434.  7.  British  Society  for
Haematology. Guideline for the Laboratory Diagnosis of Iron Deficiency in Adults and Children. Br J
Haematol. 2022;196:523–529. 8. Houston BL, Hurrie D, Graham J, et al. Efficacy of iron supplementation
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on fatigue in non-anemic iron-deficient adults: systematic review. BMJ Open. 2018;8:e019240. 9. Miles
LF, Litton E, Imberger G, Story D. Intravenous iron therapy for non-anaemic, iron-deficient adults.
Cochrane Database Syst Rev. 2019;12:CD013084. 10. da Silva Lopes K, Yamaji N, Rahman MO, et al.
Nutrition-specific interventions for preventing and controlling anaemia: overview of systematic reviews.
Cochrane Database Syst Rev. 2021;9:CD013092.
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