Assessing the Effect of a Mineral-enriched Powder on Iron Deficiency in Women of Reproductive Age

Study Overview
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Brief Summary
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The goal of this clinical trial is to determine if taking a mineral-enriched powder can raise blood iron levels compared to a placebo powder in reproductive-aged women with iron deficiency. The main questions it aims to answer are: Does the mineral-enriched powder raise blood iron levels compared to a placebo powder in women when it is taken every day for six months? How many participants still have iron deficiency after six months of taking the mineral-enriched powder compared to a placebo powder? Participants in this clinical trial will drink the mineral-enriched powder containing ferrous iron and zinc sulphate monohydrate or a placebo powder mixed with 1 litre of water daily for six months. The placebo is a look-alike substance that does not contain active ingredients (iron and zinc). Participants will also have to: Complete an online study diary every two weeks for six months Provide a blood sample once a month for six months Attend three in-person visits with a researcher, at enrolment (baseline), midline (three months), and endline (six months) Complete three sets of online questionnaires (following each in-person visit) Complete three sets of dietary assessments (following each in-person visit) Provide three stool samples (following each in-person visit)

Official Title
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Randomised Controlled Trial to Assess the Effect of a Mineral-enriched Powder on Iron Deficiency in Women of Reproductive Age

Conditions
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Iron Deficiency, Iron Deficiency Anaemia

Intervention / Treatment
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* Other: Mineral-enriched powder
* Other: Placebo powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-pregnant and non-lactating English speaking with the ability to give informed consent 18-35 years of age (inclusive) Women who are biologically female Iron deficient (SF >/=12μg/L and </=30 μg/L). Note: there is currently poor consensus on diagnostic criteria for iron deficiency based on SF concentrations. Current recommendations range from 15 μg/L to 100 μg/L. Hb >/=110 g/L Willing and able to agree to the requirements and lifestyle restrictions of this study Able to understand and read the questionnaires in English and carry out all study-related procedures Located in the greater Ottawa area and a resident of Ontario Exclusion Criteria: Individuals who are lactating, pregnant, or planning to become pregnant during the study Individuals who are not maintaining adequate birth control measures Adequate birth control measures include any option that will adequately prevent pregnancy including: contraceptives, lifestyle choices, complete abstinence, or as a result of other medical methods, procedures, or conditions Have a known sensitivity, intolerability, or allergy to any of the study products or their excipients Are using vitamin and mineral supplements containing iron and/or zinc SF concentrations <12 μg/L or >30 μg/L Having moderate or severe anaemia (Hb <109 g/L) Expecting to change diet and exercise regimen in the next 6 months Are frequent blood donors Have donated blood in the last four months Donate blood more than two to three times per year Had major surgery in the past three months Have planned surgery during the course of the study History of problematic alcohol or substance use in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program) Use of investigational product(s) in another research study within 30 days prior to the baseline visit or during the study duration Using any of the following drugs: Antacids or proton pump inhibitors, H2 blockers Salicylates, aspirin, corticosteroids, nonsteroidal anti-inflammatory drugs Anticoagulants, antiplatelet compounds Drugs with known contraindication with iron supplementation or fortification Antiviral medications Levothyroxine (Synthroid) Known medical history of specific conditions including: Gastrointestinal disorders: celiac disease, ulcerative colitis, and Crohn's disease Gastric cancer and gastric polyps Colon cancer Diverticular bleeding Inflammatory bowel diseases Angiodysplasia Helicobacter pylori infection Hookworm (Ancylostoma duodenale and Necator americanus) Defects of hemostasis (hereditary hemorrhagic telangectasia, von Willebrand disease) Gastrectomy, duodenal bypass, bariatric surgery Erythropoiesis-stimulating agent therapy Chronic kidney disease Hemochromatosis Hemoglobinopathies Blood clotting disorder Have any other active or unstable medical conditions or use of medications/supplements/ therapies that according to the scientific literature, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant or the quality of the study data.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind randomised placebo-controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active intervention<br>Mineral-enriched powder | Other: Mineral-enriched powder<br>* Mineral-enriched powder Mineral-enriched powder to allow for at-home fortification of beverages with 5 mg of ferrous iron and 10 mg of zinc sulfate monohydrate<br>|
| Placebo Comparator: Placebo<br>Placebo powder | Other: Placebo powder<br>* Placebo powder which is identical to the mineral- enriched powder, but does not contain the active ingredients (ferrous iron and zinc sulfate monohydrate)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum ferritin (SF) concentrations between active intervention and placebo groups at endline (six months). Proportion of participants remaining iron deficient between active intervention and placebo groups at six months. | SF concentrations will be measured using standard clinical lab assay. | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SF concentrations from enrolment (baseline), to midline (three months), and endline (six months). | SF concentrations will be measured using standard clinical lab assay. | Baseline, three months, six months | 
| Change in haemoglobin (Hb) concentrations from enrolment (baseline), to midline (three months), and endline (six months). | Hb concentrations will be measured using standard clinical lab assay. | Baseline, three months, six months | 
| Levels of metabolites (circulating metabolome) at baseline, three months, and six months. | Functional metabolites in plasma will be measured by Liquid Chromatography-Mass Spectrometry (LC-MS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). | Baseline, three months, six months | 
| Concentrations of key circulating pro-inflammatory biomarkers at baseline, three months, and six months. | Plasma pro-inflammatory biomarkers will be measured using standard protocols via multi-plex assay (Human Cytokine 27-plex Assay, BioRad) which includes biomarkers such as TNF-alpha, IL-6, MCP-1. The assay will be conducted, and biomarkers measured according to manufacturer's guidelines. | Baseline, three months, six months | 
| Dietary recall: proportion of participants meeting dietary reference intakes at baseline, three months, and six months. | Mean food and nutrient intakes will be used to determine proportion of participants meeting dietary reference intakes. Dietary recalls will be conducted using the Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24) Canada 2018. This tool measures all food and beverages consumed over a 24-hour period. Dietary recalls will be considered complete if participants provide a minimum of two days of 24-hour recall. | Baseline, three months, six months | 
| Dietary recall: dietary patterns at baseline, three months, and six months. | Mean food and nutrient intakes will be used to determine dietary patterns of foods known to alter iron absorption. | Baseline, three months, six months | 
| Dietary recall: Healthy Eating Index (HEI) at baseline, three months, and six months. | Mean food and nutrient intakes will be used to determine HEI scores. | Baseline, three months, six months | 
| Dietary recall: Dietary Inflammatory Index (DII) at baseline, three months, and six months. | Mean food and nutrient intakes will be used to determine DII scores. | Baseline, three months, six months | 
| Self-reported perceptions of health at baseline and six months. | Proportion of participants reporting overall good health status will be measured at baseline and at six months. A descriptive health profile will be generated based on health dimensions in both the active intervention and placebo groups. Number of patients, proportions of categorical responses for each health dimensions, including the severity of the health concern will be derived. The investigators will explore significance of change in health profile within each group and significance of the difference between the active intervention and placebo groups at six months. The investigators will assess associations of health profile with adherence to study regimen. | Baseline, six months | 
| Feasibility: Adherence to the consumption regimen for the regular use of the powder. | Proportion of participants with >80% adherence (defined as preparation and consumption of the powder on at least 4 days per week or a minimum of every second day for the duration of the trial) will be measured bi-weekly for the duration of the trial. Adherence will be determined using the study diary, in which participants will report which days they consumed the study product and which days they did not. Adherence will be reported by participants bi-weekly for the duration of the study. | Bi-weekly through study completion, approximately 7 months | 
| Feasibility: Adherence to the consumption regimen for the regular use of the powder at three months and six months. | Proportion of unused powder sachets will be measured at three and six months. Participants will be asked to return all used (opened) and unused (unopened) powder sachets at three months and six months. Proportion of unused sachets will be calculated. | Baseline, three months, six months | 
| Feasibility: Self-reported barriers to use of the powder. | Proportion of participants reporting perceived barriers to use of the study product at six months. Qualitative summary of types of perceived barriers at six months. | Six months | 
| Palatability. | Palatability (i.e. odour, colour, and taste assessments) collected at six months. Palatability assessments of the study product will be conducted at six months using a 9-point hedonic scale to generate palatability scores (where >/=5 indicates that the solution was liked). Differences in participant palatability scores (for colour, odour, sweet, sour, bitter, salty, umami and overall liking) and proportion of participants willing to drink the sample daily will be used to assess the palatability of the powder, show whether the powder is accepted by consumers, and document relationships between palatability and adherence. | Six months | 
| Economic: Overall health status. | Overall health status will be measured by the EuroQol-5D visual analogue scale (EQ-5D VAS) at six months. The EQ-5D VAS provides a score of 0 to 100, where 0 represents the worst imaginable health status and 100 represents the best imaginable health status. | Six months | 
| Economic: Health state/health state index. | Health state values will be measure by EuroQol-5D (EQ-5D) at six months. Health state values will be used to generate health state index score using Canadian valuation of EQ-5D health states. | Six months | 
| Economic: Quality adjusted life years (QALYs). | Health state index scores derived from the EuroQol-5D (EQ-5D) at six months will be used to calculate quality-adjusted life years (QALYs), which will be used to perform cost effectiveness analysis. | Six months | 
| Safety (adverse events/harms). | Proportion of adverse events (AEs) and proportion of withdrawals from the study due to harms will be measured at baseline, three months, six months, and approximately seven months (four weeks post study end). AE/harms monitoring will occur bi-weekly for the duration of the study and up to four weeks after last study visit for unresolved AEs. | Baseline, three months, six months, and seven months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron deficiency, Iron deficiency anaemia, Iron fortification, Reproductive-aged women