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Trial registered on ANZCTR


Registration number
ACTRN12623000529640p
Ethics application status
Submitted, not yet approved
Date submitted
5/05/2023
Date registered
19/05/2023
Date last updated
19/05/2023
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] 309606 0
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 329918 0
Condition category
Condition code
Blood 326826 326826 0 0
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] 326028 0
Early detection / Screening
Intervention code [2] 326090 0
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] 334679 0
Serum ferritin
Timepoint [1] 334679 0
0. 4. 8 and 12 weeks following the supplement commencement.
Secondary outcome [1] 421633 0
Cumulative symptom score using a 3 points scale (mild, moderate and severe)
Timepoint [1] 421633 0
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?
No
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
Not yet recruiting
Date of first participant enrolment
Anticipated
15/08/2023
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313786 0
University
Name [1] 313786 0
Australian Catholic University
Country [1] 313786 0
Australia
Primary sponsor type
University
Name
Australian Catholic University
Address
Level 5
215 Spring Street,
Melbourne, Victoria, 3000
Country
Australia
Secondary sponsor category [1] 315619 0
None
Name [1] 315619 0
Address [1] 315619 0
Country [1] 315619 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312954 0
Australian Catholic University
Ethics committee address [1] 312954 0
Level 5
215 Spring Street,
Melbourne, Victoria 3000
Ethics committee country [1] 312954 0
Australia
Date submitted for ethics approval [1] 312954 0
04/05/2023
Approval date [1] 312954 0
Ethics approval number [1] 312954 0

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 126466 0
Dr Alannah McKay
Address 126466 0
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5
215 Spring Street
Melbourne, Victoria, 3000
Country 126466 0
Australia
Phone 126466 0
+61 439708968
Fax 126466 0
Email 126466 0
alannah.mckay@acu.edu.au
Contact person for public queries
Name 126467 0
Dr Alannah McKay
Address 126467 0
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5
215 Spring Street
Melbourne, Victoria, 3000
Country 126467 0
Australia
Phone 126467 0
+61 439708968
Fax 126467 0
Email 126467 0
alannah.mckay@acu.edu.au
Contact person for scientific queries
Name 126468 0
Dr Alannah McKay
Address 126468 0
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5
215 Spring Street
Melbourne, Victoria, 3000
Country 126468 0
Australia
Phone 126468 0
+61 439708968
Fax 126468 0
Email 126468 0
alannah.mckay@acu.edu.au

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.
alannah.mckay@acu.edu.au


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
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