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Trial registered on ANZCTR

Registration number

ACTRN12623000529640

Ethics application status

Approved

Date submitted

5/05/2023

Date registered

19/05/2023

Date last updated

2/08/2024

Date data sharing statement initially provided

19/05/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Examining the efficacy of different iron supplements in women

Scientific title

Examining the efficacy of different iron supplements (Maltofer and Ferrograd C) in women with low serum ferritin concentrations

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

The WISE study (Women and Iron Supplementation Efficacy)

Linked study record

Health condition

Health condition(s) or problem(s) studied:

iron deficiency

Condition category

Condition code

Blood

Anaemia

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

1 x Maltofer Iron Tablets per day for 12 weeks. A single supplement contains 370 mg iron polymaltose (equivalent to 100 mg or elemental iron).

Adherence will be monitored via completion of a daily survey, where participants will be asked to record what time of day (if applicable) they took the supplement. Empty supplement bottles will also be returned at 4-week intervals.

Subjects will be allocated to supplement group based on a requirement to match serum ferritin levels between supplement groups (Ferrograd C vs Maltofur) and cohort (endurance athletes, team sport athletes, active women and menopausal women). This will occur by a CI involved not involved in the data collection phase of the study. The TMPRSS6 rs855791 (2321 C>T) polymorphism will be analysed at the screening stage in women (via the same venous blood sample), with polymorphism type having no bearing or impact on the drug allocation.

Intervention code [1]

Early detection / Screening

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

1 x Ferrograd C. tablet per day for 12 weeks. A single supplement contains 325 mg of ferrous sulfate (equivalent to 105 mg of elemental iron) in addition to sodium ascorbate (equivalent to 500 mg of Vitamin C).

Adherence will be monitored via completion of a daily survey, where participants will be asked to record what time of day (if applicable) they took the supplement. Empty supplement bottles will also be returned at 4-week intervals.

Control group

Active

Outcomes

Primary outcome [1]

Serum ferritin

Timepoint [1]

0. 4. 8 and 12 weeks following the supplement commencement.

Secondary outcome [1]

Cumulative symptom score using a 3 points scale (mild, moderate and severe)

Timepoint [1]

assessed daily for 12 weeks following the supplement commencement

Eligibility

Key inclusion criteria

Females with serum ferritin concentrations below 50 ug/L.. Must also fit one of the below groups:
1. Female endurance athletes, aged 18-40 years old, must be running ~40 km per week or more; naturally menstruating;
2. Team sport athletes, aged 18-40 years old, must be participating in structured training at least 3 times/ week; naturally menstruating.
3. Active Women, aged 18-40 years old, naturally menstruating; must meet WHO’s criteria for physically active, however not meeting the training threshold or competing in endurance/team sports.
4. Postmenopausal women, aged 40-70 years old, deemed post-menopausal; not using hormonal replacement therapy; must meet WHO’s criteria for physically active, however not meeting the training threshold or competing in endurance/team sports.

Minimum age

18 Years

Maximum age

70 Years

Sex

Females

Can healthy volunteers participate?

Key exclusion criteria

The exclusion criteria for all participants includes use of hormonal contraception, pregnant, chronic diseases (i.e., diabetes, cancer, heart diseases) and/or a recent iron infusion (within 12 weeks). All participants must be willing to abstain from oral iron supplementation for 14 days prior to the first measurement.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Bio-equivalence

Statistical methods / analysis

Based on previous work assessing the efficacy of Maltofer compared to ferrous sulphate in pregnant women (Ortiz et al., 2011), an a priori power analysis suggests that 34 participants in each group is required to determine a difference in serum ferritin after supplementation (critical t=2.0, power =0.8, p=0.05). We will recruit 40 subjects in each group to ensure sufficient power, which will be equally recruited from the 4 cohorts of women (i.e. n=10 from each group). Linear mixed models will be used for analysis, with serum ferritin as a response varaible, supplement type (Maltofer vs Ferrograd) and time (0, 4, 8 and 12 weeks) as fixed effects and group as a random effect).

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

15/08/2023

Actual

15/08/2023

Date of last participant enrolment

Anticipated

31/12/2024

Actual

Date of last data collection

Anticipated

31/03/2025

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

University

Name [1]

Australian Catholic University

Address [1]

Level 5
215 Spring Street,
Melbourne , Victoria, 3000

Country [1]

Australia

Primary sponsor type

University

Name

Australian Catholic University

Address

Level 5
215 Spring Street,
Melbourne, Victoria, 3000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Australian Catholic University

Ethics committee address [1]

Level 5
215 Spring Street, 
Melbourne, Victoria 3000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

04/05/2023

Approval date [1]

31/07/2023

Ethics approval number [1]

2023-1890HC

Summary

Brief summary

Iron deficiency is one of the most common health conditions globally, and disproportionally affects women, comparative to men (Pasricha et al., 2021). Specifically, the menstrual cycle can negatively affect iron regulation, with low-estrogen periods of been prohibitive for iron absorption and menstrual blood loss resulting in a direct, and often substantial loss of body iron (McKay et al., 2022). Additionally, high exercise volumes can also be detrimental to iron status, with direct iron losses (via GI bleeding, haemolysis and sweat) and exercise-induced decreases in iron absorption been contributors to the high prevalence of iron deficiency in athletic populations (Peeling et al., 2008). Accordingly, female athletes need to combat both the sex- and exercise-associated challenges to iron regulation, making them a ‘high risk’ cohort for iron deficiency. 

One approach for correcting an iron deficiency is to use oral iron supplementation. A conventional supplementation regime consists of daily ferrous sulphate dose (~100 mg of elemental iron), usually found in combination with a source of vitamin C which typically increases an athlete’s iron stores by 30-50% over a 6–8-week period (Dawson et al., 2006; Hinton et al., 2000). However, it is not uncommon for individuals to report high levels of gastrointestinal distress from this treatment, especially athletes. Other formulations have been identified which claim to reduce the side effects associated with iron ingestion. One such formulation, is an iron(III)-hydroxide polymaltose complex (Maltofer), which has shown good efficacy and reduced side effects in pregnant women (Ortiz et al., 2011), however it’s use in athlete cohorts has not yet been determined. 

Accordingly, this study will assess to efficiency of different iron formulations in different cohorts of women with varying exercise loads and menstrual statuses. It is hypothesised that both supplements will be equally effective at increasing iron stores, however Maltofer consumption will be associated with lower GI complaints. Furthermore, we hypothesise that iron stores will be repleted faster in generally active, compared to athlete cohorts, and that menopausal women will have the greatest increase in their iron stores after 12 weeks. Collectively, this work may highlight the need to develop athlete-specific strategies for the treatment iron deficiency. 

The aims of this project are:
1.	To assess the efficacy of two different iron formulations (Ferrograd C and Maltofer) on the treatment of low iron stores in women.
2.	To compare the efficacy of oral iron supplementation in different cohorts of women.
3.	To assess the relationship between iron status, supplement efficacy and the TMPRSS6 rs855791 (2321 C>T) polymorphism in women.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Alannah McKay

Address

Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5
215 Spring Street
Melbourne, Victoria, 3000

Country

Australia

Phone

+61 439708968

Fax

[email protected]

Contact person for public queries

Name

Alannah McKay

Address

Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5
215 Spring Street
Melbourne, Victoria, 3000

Country

Australia

Phone

+61 439708968

Fax

[email protected]

Contact person for scientific queries

Name

Alannah McKay

Address

Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5
215 Spring Street
Melbourne, Victoria, 3000

Country

Australia

Phone

+61 439708968

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Serum ferritin concentrations by group.

When will data be available (start and end dates)?

start date: once the study is published in a peer-reviewed journal
end date: there is no end date.

Available to whom?

Academics conducting meta-analysis

Available for what types of analyses?

Meta-analysis

How or where can data be obtained?

Email request to PI.
[email protected]

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically