Effect of Ferrous iROn and cUrcumin sTatus on Inflammatory and Neurotrophic markErs

Study Overview
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Brief Summary
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INTRODUCTION: Iron is a vital nutrient for many physiological processes including DNA production, oxygen transport and neuronal processes. However, several factors limit iron absorption including: limited bioavailability of iron (dietary or supplementation sources), can be subject to dietary iron inhibitors (e.g. calcium). Excess iron can cause cellular oxidative stress in the body. Curcumin is an active component found in turmeric, known for its anti-oxidant and anti-inflammatory properties. Co-administration of iron and curcumin may influence iron, inflammatory status and/or neurotrophic markers in the body.

Detailed Description
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Intervention study with five parallel treatment groups in a randomised, double-blind, placebo-controlled design. Study population: Healthy Participants (Male or Female) will receive daily supplements (active or equivalent placebos) for 6 weeks (42 days) Biological samples (blood and urine samples) are collected at baseline visit (day 1), mid-point (day 21) and end-point (day 42). In addition, pertinent questionnaires (Visual Analogue Scale-Fatigue [VAS-F] and oral iron supplement questionnaire will be collected at the aforementioned time points.

Official Title
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The Effect of HydroCurc™ Curcumin and Ferrous Iron Supplementation on Iron Status and Inflammatory and Neurotrophic Marker Levels in Healthy Adults

Conditions
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Iron Deficiency (Without Anemia)

Intervention / Treatment
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* Dietary Supplement: Ferrous Sulphate 65 mg
* Dietary Supplement: Curcumin
* Other: Placebo (Ferrous Sulphate)
* Other: Placebo (Curcumin)
* Dietary Supplement: Ferrous Sulphate 18mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males & Females (18-40 years of age) Healthy subjects Exclusion Criteria: <18 years or >40 years Dieters Consumption of >21 serving of alcohol/week Any allergies/health issues related to items being ingested Any serious illnesses or those on medication Any pregnant or lactating women Any women who are trying to conceive Any women taking contraceptive medication Any gastrointestinal disorders Any chronic menstrual disorders Any subjects who have undergone the menopause or undergoing the perimenopause transition Any eating disorders Any depression/mental disorders Any abnormal blood pressure levels Those with deficient/excess/abnormal iron levels according to United Kingdom (UK) guidelines &/or haemochromatosis

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Allocation: Randomisation (block) Intervention Model: Parallel, Randomised placebo-controlled design Masking: Double-blind
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FS65_Curc<br>Ferrous Sulphate (65 mg/day elemental iron) and Curcumin 500 mg/day | Dietary Supplement: Ferrous Sulphate 65 mg<br>* Oral ferrous salt supplement Ferrous Sulphate 200 mg (equiv. 65 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules<br>* Other names: Ferrous Sulfate;Dietary Supplement: Curcumin<br>* HydroCurc™ 500 mg formulated curcumin At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)<br>* Other names: Curcuma longa;|
| Placebo Comparator: FS65_Plac<br>Ferrous Sulphate (65 mg/day elemental iron) and Placebo (Curcumin placebo [cellulose]) | Dietary Supplement: Ferrous Sulphate 65 mg<br>* Oral ferrous salt supplement Ferrous Sulphate 200 mg (equiv. 65 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules<br>* Other names: Ferrous Sulfate;Other: Placebo (Curcumin)<br>* Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)<br>|
| Placebo Comparator: FS0_Plac<br>Placebo (Ferrous Sulphate placebo [cellulose]) and Placebo (Curcumin placebo [cellulose]) | Other: Placebo (Ferrous Sulphate)<br>* Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)<br>Other: Placebo (Curcumin)<br>* Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)<br>|
| Placebo Comparator: FS18_Plac<br>Ferrous Sulphate (18 mg/day elemental iron) and Placebo (Curcumin placebo [cellulose]) | Other: Placebo (Curcumin)<br>* Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)<br>Dietary Supplement: Ferrous Sulphate 18mg<br>* Oral ferrous salt supplement Ferrous Sulphate 55 mg (equiv. 18 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules<br>* Other names: Ferrous Sulfate;|
| Active Comparator: FS18_Curc<br>Ferrous Sulphate (18 mg/day elemental iron) and Curcumin 500 mg/day | Dietary Supplement: Curcumin<br>* HydroCurc™ 500 mg formulated curcumin At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)<br>* Other names: Curcuma longa;Dietary Supplement: Ferrous Sulphate 18mg<br>* Oral ferrous salt supplement Ferrous Sulphate 55 mg (equiv. 18 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules<br>* Other names: Ferrous Sulfate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated inflammation | Marker: Interleukin 6 (pg/mL), Interleukin 10 (pg/mL), Interleukin 1 beta (pg/mL) | Change in Interleukin 6, Interleukin 10 and Interleukin 1 beta (ELISA) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated inflammation | Tumour Necrosis Factor alpha (pg/mL) | Change in Tumour Necrosis Factor alpha (ELISA) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated inflammation | Marker: C-Reactive Protein (g/L) | Change in C-Reactive Protein (immunoassay) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated lipid peroxidation | Marker: thiobarbituric acid reactive substances (μM) | Change in thiobarbituric acid reactive substances (ELISA) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated acute iron absorption | Marker: serum iron (μmol/L) | Change in serum iron (colorimetric analyser) from 0 and 180 minutes following supplementation | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated acute iron absorption | Marker: total iron binding capacity (μmol/L) | Change in total iron binding capacity (colorimetric analyser) from 0 and 180 minutes following supplementation | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status | Marker: serum iron (μmol/L) | Change in serum iron (colorimetric analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status | Marker: total iron binding capacity (μmol/L) | Change in total iron binding capacity (colorimetric analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status | Marker: Ferritin (ng/mL) | Change in ferritin (immunoassay) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status | Marker: Haemoglobin (g/dL) | Change in haemoglobin (whole blood analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status | Marker: Red blood cells (M/μL) | Change in red blood cells (whole blood analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated neurotrophic levels | Marker: Brain derived neurotrophic factor (BDNF) (ng/mL) | Change in BDNF (ELISA) from baseline to endpoint from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated gastrointestinal effects | Subjective analysis including: Oral Iron Supplement Questionnaire | Change in reported subjective gastrointestinal effects from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated perception of fatigue | Subjective analysis including: Visual Analogue Scale for Fatigue (VAS-F). Scores range from 0 to 100 (the higher the score the greater the level of fatigue) | Change in VAS-F from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 
| To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated perception of fatigue | Subjective analysis including: Fatigue Severity Scale (FSS). The total score of all answers indicates level of fatigue (a total score above ≥ 36 indicates fatigue). | Change in FSS from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nutraceutical, anti-oxidant, oxidative status, ferrous sulphate, curcumin, inflammatory status, turmeric, gastrointestinal, fatigue, iron, Hydrocurc, supplement