Iron Absorption From Encapsulated Iron Sulphate in Microspheres

Study Overview
=================
Brief Summary
-----------------
Food fortification has shown to be efficacious to alleviate the burden of micronutrient deficiencies. Ensuring the bioavailability of iron and maintaining the sensory quality and stability of the fortified food and other added micronutrients remains a challenge. Soluble iron compounds cause minor organoleptic changes in foods but their bioavailability in man is rather low. Water-soluble iron compounds, such as ferrous sulphate (FeSO4), are the compounds in which the iron is most bioavailable; however, they often cause unfavorable sensory changes. Encapsulation of iron has excellent potential for overcoming unwanted sensory changes and iodine losses in salt, while maintaining acceptable bioavailability. In the present project, we would like to investigate the iron bioavailability from a new formulation of encapsulated iron sulphate based on hyaluronic acid (HA) and a polymer from the eudragit family.

Official Title
-----------------
The Effect of Encapsulation Material and Encapsulated Micronutrients on Iron Absorption in Iron Depleted Women Consuming Iron Fortified Bread.

Conditions
-----------------
Iron-deficiency

Intervention / Treatment
-----------------
* Dietary Supplement: free FeSO4
* Dietary Supplement: free FeSO4 and empty microspheres
* Dietary Supplement: free FeSO4 and hylauronic acid
* Dietary Supplement: free FeSO4 and eudragit polymer
* Dietary Supplement: encapsulated FeSO4 3.2%
* Dietary Supplement: encapsulated FeSO4 20%
* Dietary Supplement: encapsulated FeSO4 3.2%, encapsulated Vitamin A
* Dietary Supplement: encapsulated FeSO4 3.2%, encapsulated Vitamin A, free Folic Acid
* Dietary Supplement: FeSO4 embedded in Hyaluronic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female, 18 to 40 years old Marginal iron status (PF <25 ng/ml) Body weight < 65 kg Normal body Mass Index (18.5 - 25 kg/m2) Signed informed consent Exclusion Criteria: Pregnancy (assessed by a pregnancy test) / intention to become pregnant Lactating up to 6 weeks before study initiation Moderate or severe anaemia (Hb < 9.0 g/dL) Elevated C reactive Protein (CRP) (> 5.0 mg/L) Any metabolic, gastrointestinal kidney or chronic disease such as diabetes, hepatitis, hypertension, cancer or cardiovascular diseases (according to the participants own statement) Continuous/long-term use of medication during the whole study (except for contraceptives) Consumption of mineral and vitamin supplements within 2 weeks prior to 1st meal administration Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 4 months Earlier participation in a study using Fe stable isotopes or participation in any clinical study within the last 30 days Participant who cannot be expected to comply with study protocol (e.g. not available on certain study appointments or difficulties with blood sampling)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: free FeSO4<br>wheat bread fortified with free FeSO4 | Dietary Supplement: free FeSO4<br>* Testmeal with free FeSO4<br>|
| Experimental: free FeSO4 and empty microspheres<br>wheat bread fortified with free FeSO4, and empty microspheres | Dietary Supplement: free FeSO4 and empty microspheres<br>* Testmeal with free FeSO4 and empty micropsheres<br>|
| Experimental: free FeSO4 with eudragit polymer<br>wheat bread fortified with free FeSO4, and eudragit polymer | Dietary Supplement: free FeSO4 and eudragit polymer<br>* Testmeal with free FeSO4 and eudragit polymer<br>|
| Experimental: free FeSO4 with Hyaluronic Acid<br>wheat bread fortified with free FeSO4, and hyaluronic acid | Dietary Supplement: free FeSO4 and hylauronic acid<br>* Testmeal with free FeSO4 and hyaluronic acid<br>|
| Experimental: encapsulated FeSO4 3.2%<br>wheat bread fortified with encapsulated FeSO4 in a microsphere with 3.2% Fe loading | Dietary Supplement: encapsulated FeSO4 3.2%<br>* Testmeal with encapsulated FeSO4 with 3.2% Fe loading<br>|
| Experimental: encapsulated FeSO4 20%<br>wheat bread fortified with encapsulated FeSO4 in a microsphere with 20% Fe loading | Dietary Supplement: encapsulated FeSO4 20%<br>* Testmeal with encapsulated FeSO4 with 20% Fe loading<br>|
| Experimental: encapsulated FeSO4 3.2%, encap. Vitamin A<br>wheat bread fortified with encapsulated FeSO4 in a microsphere with 3.2% Fe loading, and encapsulated Vitamin A as microspheres | Dietary Supplement: encapsulated FeSO4 3.2%, encapsulated Vitamin A<br>* Testmeal with encapsulated FeSO4 with 3.2% Fe loading, and encapsulated Vitamin A<br>|
| Experimental: encapsulated FeSO4 3.2%, encap. Vitamin A, free folicacid<br>wheat bread fortified with encapsulated FeSO4 as microsphere with 3.2% Fe loading, encapsulated Vitamin A as microspheres and free folic acid | Dietary Supplement: encapsulated FeSO4 3.2%, encapsulated Vitamin A, free Folic Acid<br>* Testmeal with encapsulated FeSO4 with 3.2% Fe loading, and encapsulated Vitamin A, with free folic acid.<br>|
| Experimental: FeSO4 embedded in Hyaluronic Acid<br>wheat bread fortified with FeSO4 that is embedded in hyaluronic acid. | Dietary Supplement: FeSO4 embedded in Hyaluronic acid<br>* Testmeal with FeSO4 embedded in Hyaluronic acid<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the isotopic ratio of iron in blood at week 2 | The change in the isotopic ratio of iron will be measured after the administration of test meal including iron isotopes. | baseline, 2 weeks | 
| Change from week 2 in the isotopic ratio of iron in blood at week 4 | The change in the isotopic ratio of iron will be measured after the administration of test meal including iron isotopes. | 2 weeks, 4 weeks | 
| Change from week 4 in the isotopic ratio of iron in blood at week 6 | The change in the isotopic ratio of iron will be measured after the administration of test meal including iron isotopes. | 4 weeks, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemoglobin | Haemoglobin of each timepoint | baseline, weeks 2, 4 and 6 | 
| Plasma Ferritin | Plasma Ferritin of each timepoint | baseline, weeks 2, 4 and 6 | 
| inflammation marker | C reactive Protein of each timepoint | baseline, weeks 2, 4 and 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Iron deficiency, Iron fortification, Iron encapsulation