## Protocol Section
### Identification Module
**NCT ID:** NCT06425796

**Acronym:** ADIPREG

**Brief Title:** Adiposity and Iron Requirements in Pregnancy

**Official Title:** Impact of Maternal Adiposity on Maternal Iron Status and Requirements: a Randomised Intervention Study

#### Organization Study ID Info
**ID:** FCBMS-23-259
#### Organization
**Class:** OTHER
**Full Name:** University of Ulster
### Status Module
#### Completion Date
**Date:** 2026-01-19

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-01-19

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-20

**Type:** ESTIMATED

**Status Verified Date:** 2024-03

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-21
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** Northern Health & Social Care Trust (NHSCT)

**Class:** UNKNOWN

**Name:** Solvotrin Therapeutics - Active Iron

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Ulster

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study aims to explore how body fat influences the response to either 25 or 50 mg of daily iron supplements during pregnancy. We will conduct a double-blind randomized controlled intervention study involving 312 pregnant women recruited from antenatal clinics in the Northern Trust Area. Participants will be randomly assigned to receive either 25 or 50 mg of iron per day from 12 weeks of pregnancy until delivery, using the Active Iron supplement brand. Blood samples will be collected at 12, 28 and 36 weeks gestation and umbilical cord blood will be collected at delivery. Anthropometric measurements will be taken at each visit, and participants will complete questionnaires on various aspects of health and lifestyle, mental health, gastrointestinal symptoms, and compliance.

**Detailed Description:** The main aim of this study is to investigate the influence of adiposity on the difference in response to 25 or 50 mg of daily iron supplementation during pregnancy. The primary aim is to determine the influence of maternal adiposity on adjusted maternal ferritin concentrations in response to 25 mg or 50 mg iron supplementation in pregnancy. The secondary outcomes of this study include: investigating the impact of maternal body fat on various maternal iron biomarkers (such as haemoglobin, soluble transferrin receptor, hepcidin, transferrin saturation, and other haematological markers) in response to either 25 mg or 50 mg iron supplementation during pregnancy, evaluating changes in adjusted ferritin concentrations and other iron markers throughout pregnancy relative to the dosage of iron supplementation received, determining the effect of maternal body fat on neonatal iron biomarkers in response to maternal iron supplementation, assessing changes in markers of inflammation in response to iron supplementation during pregnancy, and examine changes in mental health scores in response to iron supplementation during pregnancy.

This is a double-blind randomised controlled intervention study, in which 312 pregnant women with singleton pregnancy, without current complications, aged ≥ 18 years and BMI ≥ 18.5 kg/m2 will be recruited. Participants who are taking multivitamins will be included. They will be asked to discontinue any current supplementation. Pregnant women with anaemia, iron deficiency, high risk of iron overload, history of bariatric surgery, who are planning home birth, are currently involved in another research study, and those who cannot speak or understand English language will be excluded.

Blood samples and anthropometric and body composition measurements will be taken at different points in the pregnancy (12, 28, 36 gestational weeks) and an umbilical cord blood sample at the time of birth. Blood concentrations of iron and inflammation markers will be analysed. General, dietary intake and lifestyle information will be collected, through a Health and Lifestyle questionnaire and a 4-day diary. Additionally, participants will complete a questionnaire about their mental health and gastrointestinal symptoms. The compliance of the supplementation will be evaluated at each timepoint. Additionally, participants will receive a telephone call to evaluate possible adverse effects and compliance of the supplementation between the timepoints (18, 24 and 32 weeks of gestation). In the event that a participant has been prescribed iron treatment, anaemia diagnosis at any time during pregnancy or the occurrence of any adverse outcome such as miscarriage, the participant will be withdrawn from the study. Electronic forms prepared in RedCap will be used to collect data.

### Conditions Module

**Conditions:**

- Iron Deficiency Anemia of Pregnancy

**Keywords:**

- Iron status

- Iron Supplements

- Pregnancy

- Anaemia

- Maternal obesity

- Maternal Overweight

- Body composition

- Ferritin

- Inflammation

- Mental Health

- Neonatal anaemia

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** Double Blind: two or more parties are unaware of the intervention assignment

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 312

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Iron 25 (total 25 mg/d of iron): 2 supplements of 12.5 mg of elemental iron + 1 multivitamin supplement;

**Intervention Names:**

- Dietary Supplement: Adiposity and Iron Requirements in Pregnancy (ADIPREG)

**Label:** Iron 25

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Iron 50 (total 50 mg/d of iron): 2 supplements of 25 mg of elemental iron + 1 multivitamin supplement).

**Intervention Names:**

- Dietary Supplement: Adiposity and Iron Requirements in Pregnancy (ADIPREG)

**Label:** IRON 50

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- IRON 50

- Iron 25

**Description:** Iron 25 arm will receive: two iron supplements containing 12.5 mg of elemental iron + 1 multivitamin supplement (they will receive a total of 3 supplements per day).

Iron 50 arm will receive: two 25 mg elemental iron supplements + 1 multivitamin supplement (they will receive a total of 3 supplements per day).

The multivitamin supplement will contain folic acid, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B12, vitamin C and vitamin D. In summary, each participant will receive 3 supplements per day and instructed to take the 3 supplements together, in the morning, with breakfast. Supplements will be given to the participants when they attend for their clinic appointment. The intervention will begin at 12 gestational weeks and continue until the baby is delivered.

**Name:** Adiposity and Iron Requirements in Pregnancy (ADIPREG)

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** Assessed via ELISA analyses for ferritin concentration

**Measure:** Adjusted maternal ferritin concentrations in response to iron supplementation (ng/mL)

**Time Frame:** 16, 24 and 28 weeks after baseline

#### Secondary Outcomes

**Description:** Assessed via Direct Current sheat flow method (Sysmex)

**Measure:** Hemoglobin (g/L)

**Time Frame:** 16, 24 and 28 weeks after baseline

**Description:** Assessed via Direct Current sheat flow method (Sysmex)

**Measure:** Red blood cell count (RBC) (10^12/L)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via Direct Current sheat flow method (Sysmex)

**Measure:** Mean cell haemoglobin (MCH) (pg

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via Direct Current sheat flow method (Sysmex)

**Measure:** Mean cell volume (MCV) (fl)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via Direct Current sheat flow method (Sysmex)

**Measure:** Mean cell haemoglobin concentrations (MCHC) (g/dL)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via Direct Current sheat flow method (Sysmex)

**Measure:** Red cell distribution width (RDW) (%)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via immunoturbidimety assay

**Measure:** Transferrin (g/L)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via colorimetic assay

**Measure:** Serum iron (umol/L)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via ELISA

**Measure:** sTfR (ug/mL)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via ELISA

**Measure:** Hepcidin (pg/mL)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via ELISA

**Measure:** C-reactive protein (mg/mL)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via sandwich immunoassay

**Measure:** Pro- anti- inflammatory biomarkers: IL-1 β, IL-6, IL-10, IL-22, IL-17, TNF- α, IFN- γ (fg/mL)

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** Assessed via methylation analyses

**Measure:** Genetic variants of interest in relation to obesity and iron metabolism in response to iron supplementation.

**Time Frame:** 16, 24 and 28 weeks after baseline.

**Description:** CORE 10 questionnaire will be completed by each participant at each timepoint: CORE stands for "Clinical Outcomes in Routine Evaluation." The CORE-10 is a 10-item assesses psychological distress over the past week. The resulting score can be divided into categories with increasing severity: Healthy (0-5), low (6-10), mild (11-14), moderate (15-19), moderate-to-severe (20-24), and severe (25 and above). The score of this questionnaire will be collected as a numeric variable.

**Measure:** Mental health score in response to iron supplementation

**Time Frame:** 16, 24 and 28 weeks after baseline

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:- Pregnant women

* Age ≥ 18 years
* BMI ≥18.5 kg/m2
* Without current pregnancy complications (for example, severe bleeding, Diabetes Mellitus, hyperemesis gravidarum, ectopic and molar pregnancies)
* At least 12 Gestational Week
* Singleton pregnancy confirmed with the first ultrasound scan
* Participants who are currently taking multivitamins will be included. They will be asked to discontinue any current supplementation.

Exclusion Criteria:

* Hb \<110 g/L
* SF \<30 μg/L
* High risk of iron overload (Hb \>150 g/L, transferrin saturation \>45% or SF\> 150 μg/L)
* Participants with history of haematological, renal, liver, autoimmune disorders, malabsorptive syndromes
* Participants with history of bariatric surgery
* Participants who take steroids or anti-inflammatory treatments or drugs that affect gut absorption (proton-pump inhibitors)
* Planned home births
* Participants currently involved in another research study
* Multiple pregnancy
* Participants who do not speak English

**Gender Based:** True

**Gender Description:** only female participants are being studied

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** mt.mccann@ulster.ac.uk

**Name:** Mary T McCann, PhD

**Phone:** +4402870123969

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Coleraine

**Country:** United Kingdom

**Facility:** Ulster University,Human Intervention Studies Unit,

**State:** Co. Londonderry

**Zip:** BT521SA

#### Overall Officials

**Official 1:**

**Affiliation:** University of Ulster

**Name:** Mary McCann, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000019189

- Term: Iron Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000000747

- Term: Anemia, Hypochromic

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

### Condition Browse Module - Browse Leaves

- ID: M12701

- Name: Obesity

- Relevance: LOW

- As Found: Unknown

- ID: M10293

- Name: Inflammation

- Relevance: LOW

- As Found: Unknown

- ID: M4070

- Name: Anemia

- Relevance: HIGH

- As Found: Anemia

- ID: M20857

- Name: Anemia, Iron-Deficiency

- Relevance: HIGH

- As Found: Iron Deficiency Anemia

- ID: M2781

- Name: Iron Deficiencies

- Relevance: HIGH

- As Found: Iron Deficiency

- ID: M26186

- Name: Overweight

- Relevance: LOW

- As Found: Unknown

- ID: M2040

- Name: Obesity, Maternal

- Relevance: LOW

- As Found: Unknown

- ID: M4081

- Name: Anemia, Neonatal

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21177

- Name: Iron Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4077

- Name: Anemia, Hypochromic

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000000740

- Term: Anemia

- ID: D000018798

- Term: Anemia, Iron-Deficiency

- ID: D000090463

- Term: Iron Deficiencies

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: Lipd

- Name: Lipid Regulating Agents

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: Vi

- Name: Vitamins

- Abbrev: Mi

- Name: Mineral

### Intervention Browse Module - Browse Leaves

- ID: M4513

- Name: Ascorbic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M10533

- Name: Iron

- Relevance: LOW

- As Found: Unknown

- ID: M12476

- Name: Niacinamide

- Relevance: LOW

- As Found: Unknown

- ID: M12465

- Name: Niacin

- Relevance: LOW

- As Found: Unknown

- ID: M12479

- Name: Nicotinic Acids

- Relevance: LOW

- As Found: Unknown

- ID: M17550

- Name: Vitamin D

- Relevance: LOW

- As Found: Unknown

- ID: M6003

- Name: Cholecalciferol

- Relevance: LOW

- As Found: Unknown

- ID: M23026

- Name: Vitamin B 6

- Relevance: LOW

- As Found: Unknown

- ID: M14583

- Name: Pyridoxal

- Relevance: LOW

- As Found: Unknown

- ID: M14589

- Name: Pyridoxine

- Relevance: LOW

- As Found: Unknown

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M13124

- Name: Pantothenic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17548

- Name: Vitamin B 12

- Relevance: LOW

- As Found: Unknown

- ID: M9934

- Name: Hydroxocobalamin

- Relevance: LOW

- As Found: Unknown

- ID: M16595

- Name: Thiamine

- Relevance: LOW

- As Found: Unknown

- ID: M15085

- Name: Riboflavin

- Relevance: LOW

- As Found: Unknown

- ID: T477

- Name: Vitamin C

- Relevance: LOW

- As Found: Unknown

- ID: T447

- Name: Folinic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T455

- Name: Nicotinamide

- Relevance: LOW

- As Found: Unknown

- ID: T453

- Name: Niacin

- Relevance: LOW

- As Found: Unknown

- ID: T454

- Name: Niacinamide

- Relevance: LOW

- As Found: Unknown

- ID: T456

- Name: Nicotinic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T471

- Name: Vitamin B3

- Relevance: LOW

- As Found: Unknown

- ID: T437

- Name: Ascorbic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T442

- Name: Cholecalciferol

- Relevance: LOW

- As Found: Unknown

- ID: T479

- Name: Vitamin D3

- Relevance: LOW

- As Found: Unknown

- ID: T440

- Name: Calciferol

- Relevance: LOW

- As Found: Unknown

- ID: T474

- Name: Vitamin B6

- Relevance: LOW

- As Found: Unknown

- ID: T459

- Name: Pyridoxal

- Relevance: LOW

- As Found: Unknown

- ID: T461

- Name: Pyridoxine

- Relevance: LOW

- As Found: Unknown

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T451

- Name: Methylcobalamin

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

- ID: T472

- Name: Vitamin B5

- Relevance: LOW

- As Found: Unknown

- ID: T476

- Name: Vitamin B12

- Relevance: LOW

- As Found: Unknown

- ID: T441

- Name: Cobalamin

- Relevance: LOW

- As Found: Unknown

- ID: T444

- Name: Cyanocobalamin

- Relevance: LOW

- As Found: Unknown

- ID: T341

- Name: Iron Supplement

- Relevance: LOW

- As Found: Unknown

- ID: T464

- Name: Thiamin

- Relevance: LOW

- As Found: Unknown

- ID: T465

- Name: Thiamine

- Relevance: LOW

- As Found: Unknown

- ID: T469

- Name: Vitamin B1

- Relevance: LOW

- As Found: Unknown

- ID: T463

- Name: Riboflavin

- Relevance: LOW

- As Found: Unknown

- ID: T470

- Name: Vitamin B2

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
