Safe and Effective Delivery of Supplemental Iron to Healthy Volunteers

NCT03212677 | Completed DMC

• 1 other identifier: OPP1139998
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 2

Brief Summary

Iron deficiency-related anemia is the most common nutritional deficiency disorder in the world, mainly affecting children, women and older adults in underdeveloped countries. To combat iron deficiency, inorganic forms of iron (such as ferrous sulfate) are often used as an iron supplement. One big problem is that high levels of this kind of iron supplement produce negative health effects. This includes diarrhea, changes in the bacteria in the gut, as well as increased severity to malaria in young children in countries with high rates of that parasite. Most forms of iron are not well absorbed and, therefore, pass through the intestine to be eliminated in the stool. This unabsorbed iron can be used by gut bacteria, disturbing the balance of healthful and potentially harmful bacteria in the colon, which can increase inflammation in the body. In this study, the investigators are seeking to determine whether two new forms of iron cause fewer changes in the gut bacteria thus lowering inflammation while providing similar amounts of iron to the body. The findings from this research study are important because they will inform the development of safer treatments for iron deficiency.

Conditions

Iron

Outcome Measures

Primary Outcomes (3)

• Malaria infectivity

  Malaria (Plasmodium falciparum) infectivity of host erythrocytes will be assessed in vitro

  4 weeks

• Bacterial proliferation potential

  Bacterial proliferation potential studies will be conducted in vitro using subject plasma

  4 weeks

• Fecal calprotectin

  Fecal calprotectin will be analyzed using ELISA.

  4 weeks

Secondary Outcomes (6)

• Biochemical markers of systemic inflammation, such as plasma cytokines

  4 weeks

• Biochemical markers of intestinal inflammation, such as fecal cytokines

  4 weeks

• Intestinal microbiome

  4 weeks

• Fecal short chain fatty acids

  4 weeks

• Biochemical markers of redox stress, such as F2α-isoprostanes

  4 weeks

Study Arms (8)

Iron-deficient children

ACTIVE COMPARATOR

Previously iron-deficient children aged 6-24 months on iron therapy. Ferrous sulfate administered at 4 mg Fe/kg/d per standard of care.

Dietary Supplement: Ferrous sulfate

Non-iron-deficient children

NO INTERVENTION

Non-iron-deficient children aged 6-24 months used as a reference.

Adult Placebo

PLACEBO COMPARATOR

Iron-replete postmenopausal women, and men, receiving placebo daily for 4 weeks.

Other: Placebo

Adult Ferrous sulfate daily

EXPERIMENTAL

Iron-replete postmenopausal women, and men, receiving ferrous sulfate daily (containing 60 mg Fe per day) for 4 weeks. In Phase II, iron-replete postmenopausal women, and men, receiving ferrous sulfate daily (containing 120 mg Fe per day) for 4 weeks.

Dietary Supplement: Ferrous sulfate

Adult ferrous sulfate weekly

EXPERIMENTAL

Iron-replete postmenopausal women, and men, receiving ferrous sulfate weekly (containing 60 mg Fe per day) for 4 weeks.

Dietary Supplement: Ferrous sulfate

Adult ferrous sulfate + micronutrient

EXPERIMENTAL

Iron-replete postmenopausal women, and men, receiving ferrous sulfate + micronutrient supplement (containing 60 mg Fe per day) for 4 weeks.

Dietary Supplement: Ferrous sulfate

Adult IHAT

EXPERIMENTAL

Iron-replete postmenopausal women, and men, receiving IHAT (containing 60 mg Fe per day) for 4 weeks. In Phase II, iron-replete postmenopausal women, and men, receiving IHAT (containing 120 mg Fe per day) for 4 weeks

Dietary Supplement: IHAT

Adult Aspiron

EXPERIMENTAL

Iron-replete postmenopausal women, and men, receiving Aspiron (containing 60 mg Fe per day) for 4 weeks. In Phase II, iron-replete postmenopausal women, and men, receiving Aspiron (containing 120 mg Fe per day) for 4 weeks.

Dietary Supplement: Aspiron

Interventions

Ferrous sulfate DIETARY_SUPPLEMENT

Standard-of-care therapy for iron deficiency anaemia

Adult Ferrous sulfate daily; Adult ferrous sulfate + micronutrient; Adult ferrous sulfate weekly; Iron-deficient children

IHAT DIETARY_SUPPLEMENT

IHAT is a nanoparticle composed of three General Regarded As Safe (GRAS) substances, iron hydroxide, tartaric acid and adipic acid. The particle itself resembles the normal metabolite ferritin, which is a larger polyatomic particle. Like ferritin, IHAT can be absorbed by endocytosis, but dissociates within the enterocyte and is subsequently metabolized as ferrous iron.

Also known as: Iron hydroxide adipate tartrate

Adult IHAT

Aspiron DIETARY_SUPPLEMENT

Aspiron is a product of the natural fermentation of Koji (Aspergillus oryzae) in the presence of ferrous sulfate. The iron-rich koji biomass is heated, harvested and dried which results in the inactivation of Koji powder that contains 8-10% iron. Koji (A. oryzae) is widely used for making such foods as soy sauce, tempeh, miso, and for producing food-grade α-amylase, and is considered safe by Joint Food and Agriculture Organization of the United Nations (FAO)/WHO Committee on Food Additives and has been accepted as a GRAS constituent of food.

Also known as: Aspiron™ Natural Koji Iron

Adult Aspiron

Placebo OTHER

Cornstarch

Also known as: Melogel Cornstarch

Adult Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range: 50-80 years
• BMI range: 18-35
• Men and post-menopausal women (defined as no menses for \> 1year or S/P hysterectomy with bilateral oopherectomy)
• Typical bowel pattern: at least 1 stool every other day
• Willing to take iron and be randomized into study intervention group
• Willing to abstain from recreational drug use and consumption \> 2 alcoholic drinks per day during study participation
• Will not be undergoing colonoscopy in the 2 months before, or during the course of the study

You may not qualify if:

• Any major illness or condition that may interfere with study outcomes at the discretion of the study MD
• Personal history of G-6-P (glucose-6-phosphate dehydrogenase) deficiency
• Diabetes Type 1 \& Type 2 or use of any pharmacological treatment for diabetes
• Endocrine disorders including diabetes, unstable thyroid disease (dose adjustment of thyroid replacement in the past 6 months), adrenal disease, pheochromocytoma or parathyroid disease
• Recent history of inflammatory diseases (for example: rheumatoid arthritis, lupus)
• Use tumor necrosis factor (TNF) blockade medication, methotrexate, or other immune-modulating drugs
• Steroid use (except for non-prescription topical and nasal steroids, e.g. Flonase)
• If participant is on hormone replacement therapy with estrogen, testosterone or growth hormone, has the dosage regimen changed in the past month, or expected to change during course of study
• History of myocardial infarction, stroke or transient ischemic attack (TIA), coronary artery bypass graft, stenosis \>50% diagnosed within the past 1 year or acute unstable cardiovascular disease.
• Clotting/bleeding disorders or ongoing anticoagulant use: coumadin (warfarin), Eliquis, Xarelto, Pradaxa
• GI diseases, conditions or medications known to influence GI absorption including active peptic ulcer disease or inflammatory bowel disease (such as ulcerative colitis, Crohn's disease), pancreatic insufficiency, celiac disease, malabsorption disorders (other than lactose intolerance)
• Hx of stomach or bowel resection (other than appendectomy), gastric bypass or other bariatric weight loss procedure
• Regular use (\> 2 times per week) of acid lowering medication: antacids, proton pump inhibitors (PPI), H2 blockers
• History of eating disorder anorexia, bulimia or binge-eating in the past 5 years
• Actively undergoing dialysis

Sponsors & Collaborators

• Tufts University: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (2)

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University

Boston, Massachusetts, 02111, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Lewis ED, Ortega EF, Dao MC, Barger K, Mason JB, Leong JM, Osburne MS, Magoun L, Nepveux V FJ, Chishti AH, Schwake C, Quynh A, Gilhooly CH, Petty G, Guo W, Matuszek G, Pereira D, Reddy M, Wang J, Wu D, Meydani SN, Combs GF Jr. Safe and effective delivery of supplemental iron to healthy adults: a two-phase, randomized, double-blind trial - the safe iron study. Front Nutr. 2023 Oct 11;10:1230061. doi: 10.3389/fnut.2023.1230061. eCollection 2023.

  PMID: 37899826 DERIVED

• Lewis ED, Wu D, Mason JB, Chishti AH, Leong JM, Barger K, Meydani SN, Combs GF. Safe and effective delivery of supplemental iron to healthy older adults: The double-blind, randomized, placebo-controlled trial protocol of the Safe Iron Study. Gates Open Res. 2021 Feb 9;3:1510. doi: 10.12688/gatesopenres.13039.2. eCollection 2019.

  PMID: 33655197 DERIVED

MeSH Terms

Interventions

ferrous sulfate

Study Officials

• Simin N Meydani, DVM, PhD

  Tufts Univeristy

  PRINCIPAL INVESTIGATOR

• Gerald F Combs, PhD

  Tufts University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Provost for Research; Director, Nutritional Immunology Lab

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: July 11, 2017
• Study Start: May 17, 2017
• Primary Completion: December 30, 2021
• Study Completion: July 30, 2022
• Last Updated: April 25, 2025

Record last verified: 2021-04

Locations

US (2)