Iron Supplementation and Side Effects

July 10, 2019 updated by: Dr. Manju B. Reddy, Iowa State University

Assessment of Gastrointestinal Symptoms and Other Side Effects After Three Week Oral Ferrous Sulfate and Iron-enriched Aspergillus Oryzae Supplementation in Young Female Subjects

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Ames, Iowa, United States, 50011
        • Iowa State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Area under the serum iron curve over 8 hours
Time Frame: 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).
0,1,2,3,4,6 and 8 hours
Area under the NTBI curve over 8 hours
Time Frame: 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).
0,1,2,3,4,6 and 8 hours
Area under the percent transferrin saturation curve over 8 hours
Time Frame: 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).
0,1,2,3,4,6 and 8 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in protein carbonyls
Time Frame: 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.
Baseline and 21 days
Change in thiobarbituric acid reactive substances (TBARS)
Time Frame: 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.
Baseline and 21 days
Change in hepcidin
Time Frame: 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.
Baseline and 21 days
Change in C-reactive protein
Time Frame: 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.
Baseline and 21 days
Change in serum ferritin
Time Frame: 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.
Baseline and 21 days
Change in hemoglobin
Time Frame: 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.
Baseline and 21 days
Change in hematocrit
Time Frame: 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.
Baseline and 21 days
Change in soluble transferrin receptor (sTFR)
Time Frame: 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.
Baseline and 21 days
Change in total iron binding capacity (TIBC)
Time Frame: 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.
Baseline and 21 days
Change in glomerular filtration rate (eGFR)
Time Frame: 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.
Baseline and 21 days
Change in creatinine
Time Frame: 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.
Baseline and 21 days
Change in blood urea nitrogen (BUN)
Time Frame: 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.
Baseline and 21 days
Change in aspartate aminotransferase (AST)
Time Frame: 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.
Baseline and 21 days
Change in alanine aminotransferase (ALT)
Time Frame: 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.
Baseline and 21 days
Gastrointestinal symptoms
Time Frame: 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.
21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Iowa State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 8, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 18, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 18, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 3, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 12, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 12, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SEAS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Publication in a journal

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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