Iron Supplementation and Side Effects

• Sponsor: Iowa State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04018300
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arms: 3
• Actual Duration (Months): 3.3
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief Summary

The objective of this study is to examine patient-reported gastrointestinal side effects, as well as iron status indicators, inflammatory markers and oxidative stress following administration of ferrous sulfate and iron-enriched Aspergillus oryzae supplementation.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia; Iron Overload	Dietary Supplement: Ferrous sulfate; Dietary Supplement: Aspiron; Other: Placebo	N/A

Detailed Description

Iron deficiency anemia (IDA) afflicts more than 2 billion people globally, making it the most prevalent nutrient disorder, today. Inadequate dietary intake of iron results in consequences like cognitive decline, fatigue, abnormal growth and adverse pregnancy outcomes. These ramifications have associated burdens on economical progression due to decreased market productivity. Inorganic iron supplements like ferrous sulfate (FeSO4) are most commonly used to treat IDA, however known associated side effects occur, decreasing compliancy in individuals. Moreover, inorganic iron salts present a large bolus of iron to the intestinal lumen, resulting in non-transferrin bound iron which leads to systemic inflammation and further exacerbation of chronic diseases. Organic iron compounds have strong potential to be utilized for supplementation, however only under circumstances in which contain high absorbance. Seventeen subjects were randomized in a three-armed, double-blinded crossover design to examine the differences among three treatments (FeSO4, ASP-s and placebo). Outcomes will be to assess acute inflammatory proteins, oxidative stress, iron status indicators, non-transferrin bound iron and gastrointestinal-related side effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Three armed, cross-over, double blinded design. Fifteen subjects will be randomized to treatment FeSO4, ASP or placebo for two week per treatment. Following each treatment, will be a two week washout period whereby subjects will not consume a supplement. Baseline and final blood draws of each treatment will be collected, in addition to serum collection at 0h, 1h, 2h, 3h, 4h following one dose to determine NTBI concentration curve.Three armed, cross-over, double blinded design. Fifteen subjects will be randomized to treatment FeSO4, ASP or placebo for two week per treatment. Following each treatment, will be a two week washout period whereby subjects will not consume a supplement. Baseline and final blood draws of each treatment will be collected, in addition to serum collection at 0h, 1h, 2h, 3h, 4h following one dose to determine NTBI concentration curve.
• Masking: Double (Participant, Investigator)
• Masking Description: Treatments will be randomized to A or B. Investigators will be blinded to the corresponding treatment, in addition to the subjects being randomized to follow the sequence of supplements as ACB or BCA.
• Primary Purpose: Basic Science
• Official Title: Assessment of Gastrointestinal Symptoms and Other Side Effects After Three Week Oral Ferrous Sulfate and Iron-enriched Aspergillus Oryzae Supplementation in Young Female Subjects
• Actual Study Start Date: Jan 8, 2018
• Actual Primary Completion Date: Apr 18, 2018
• Actual Study Completion Date: Apr 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ferrous sulfate Subjects will take a 65 mg Fe capsule of ferrous sulfate, once daily for 21 consecutive days. The first treatment capsule will be consumed with a semi-purified meal (egg albumin, sugar, vanilla, maltodextrose and corn oil) and will have blood drawn hours 0, 1, 2, 3, 4, 6 and 8 post consumption. Serum will be used to determine non-transerrin bound iron, serum iron and percent saturation. Throughout the treatment period, subjects are informed to consume the capsule with food and report symptoms in an online questionnaire. Following three weeks treatment, participants return for a blood draw and oxidative stress indicators are measured. A three week washout period with placebo treatment takes place between treatment crossover.	Dietary Supplement: Ferrous sulfate; 65 mg Fe as ferrous sulfate
Experimental: Aspiron AspironTM which is an iron-enriched supplement will follow the same guidelines and protocol as ferrous sulfate arm. Equivalent 65 mg Fe per capsule will be administered to participants.	Dietary Supplement: Aspiron; 65 mg Fe as iron-enriched koji culture, called AspironTM; Other Names: Aspergillus oryzae
Placebo Comparator: Placebo Participants will follow the same description for the other two experimental treatment groups. Capsules will be given to subjects in opaque formation, therefore will be unable to differentiate the iron supplements.	Other: Placebo; Contains maltodextrin.; Other Names: Starch pill

Outcome Measures

Primary Outcome Measures

1. Area under the serum iron curve over 8 hours [0,1,2,3,4,6 and 8 hours]

   Serum iron concentrations (µM) measured over 8 hours following consumption of either Ultimine, FeSO4, or placebo capsules at baseline (0h).

2. Area under the NTBI curve over 8 hours [0,1,2,3,4,6 and 8 hours]

   NTBI (µM) concentrations measured over 8 hours following consumption of either Ultimine, FeSO4, or placebo capsules at baseline (0h).

3. Area under the percent transferrin saturation curve over 8 hours [0,1,2,3,4,6 and 8 hours]

   Percent transferrin (%) saturation concentrations measured over 8 hours following consumption of either Ultimine, FeSO4, or placebo capsules at baseline (0h).

Secondary Outcome Measures

1. Change in protein carbonyls [Baseline and 21 days]

   Change from baseline to 21 days of protein carbonyls (nmol/mL) oxidative stress after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

2. Change in thiobarbituric acid reactive substances (TBARS) [Baseline and 21 days]

   Change from baseline to 21 days of TBARS (µM) oxidative stress after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

3. Change in hepcidin [Baseline and 21 days]

   Change from baseline to 21 days of inflammatory status via hepcidin (ng/mL) after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

4. Change in C-reactive protein [Baseline and 21 days]

   Change from baseline to 21 days of inflammatory status via C-reactive protein (mg/L) after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

5. Change in serum ferritin [Baseline and 21 days]

   Change from baseline to 21 days of iron status through serum ferritin (µg/L) after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

6. Change in hemoglobin [Baseline and 21 days]

   Change from baseline to 21 days of iron status through hemoglobin (g/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

7. Change in hematocrit [Baseline and 21 days]

   Change from baseline to 21 days of iron status through hematocrit (%) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

8. Change in soluble transferrin receptor (sTFR) [Baseline and 21 days]

   Change from baseline to 21 days of iron status through sTFR (ng/mL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

9. Change in total iron binding capacity (TIBC) [Baseline and 21 days]

   Change from baseline to 21 days of iron status through TIBC (µg/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

10. Change in glomerular filtration rate (eGFR) [Baseline and 21 days]

    Change from baseline to 21 days of kidney function through eGFR (mL/min/1.73m2) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

11. Change in creatinine [Baseline and 21 days]

    Change from baseline to 21 days of kidney function through creatinine (mg/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

12. Change in blood urea nitrogen (BUN) [Baseline and 21 days]

    Change from baseline to 21 days of kidney function through BUN (mg/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

13. Change in aspartate aminotransferase (AST) [Baseline and 21 days]

    Change from baseline to 21 days of kidney function through AST (U/L) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

14. Change in alanine aminotransferase (ALT) [Baseline and 21 days]

    Change from baseline to 21 days of kidney function through ALT (U/L) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.

15. Gastrointestinal symptoms [21 days]

    Symptoms questionnaire was distributed 3 days/week over 3 weeks/treatment. Total survey per supplemental treatment included 9 surveys. Participants described how the supplement contributed to gastrointestinal distress, such as, constipation, diarrhea, fatigue, abdominal discomfort, nausea, headaches, and heartburn.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age 18-40

• Female

• BMI < 30 kg/m2

• Nonsmoker

• Non pregnant

• Non lactating

• No food allergies to wheat or dairy

• No history of gastrointestinal diseases/disorders

• Willing to discontinue use of vitamin/mineral supplements

• No medications that interfere with iron absorption

• No blood or plasma donations during study period

Exclusion Criteria:

• History of gastrointestinal diseases or disorders

• Donating blood or plasma two weeks prior to study period

• On medications interfering with iron absorption

• Food allergies to wheat or dairy

• Pregnant or lactating

• Smoker

• Anemic (< 120 g/L)

• Ferritin > 40 ug/L

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Iowa State University	Ames	Iowa	United States	50011

Sponsors and Collaborators

• Iowa State University

Investigators

• Principal Investigator: Manju B Reddy, PhD, Iowa State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Manju B. Reddy, Professor, Iowa State University
• ClinicalTrials.gov Identifier: NCT04018300
• Other Study ID Numbers: SEAS
• First Posted: Jul 12, 2019
• Last Update Posted: Jul 12, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dr. Manju B. Reddy, Professor, Iowa State University: ferrous sulfate; non-transferrin bound iron; oral iron supplement; oral iron supplement side effects
• Additional relevant MeSH terms: Anemia, Iron-Deficiency; Iron Overload

Study Results

No Results Posted as of Jul 12, 2019