Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001357943
Ethics application status
Approved
Date submitted
10/09/2020
Date registered
17/12/2020
Date last updated
7/04/2022
Date data sharing statement initially provided
17/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
IRONWOMAN- the effect of intravenous iron on performance outcomes, quality of life and mood states in iron deficient female athletes.
Scientific title
The effect of intravenous iron on performance outcomes, quality of life and mood states in iron deficient recreational female athletes: A randomised control trial.
Secondary ID [1] 302123 0
None
Universal Trial Number (UTN)
Trial acronym
IRONWOMAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Iron Deficiency 318755 0
Iron Deficiency Anaemia 318756 0
Condition category
Condition code
Public Health 316769 316769 0 0
Other public health
Blood 317509 317509 0 0
Anaemia
Metabolic and Endocrine 317510 317510 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
An intervention will be used, as per the protocol document (also described below).

The population being studied is all female athletes with iron deficiency, half of whom will be randomised to treatment of their iron deficiency. The comparators will be the interventions before and after randomisation of treatment.

Intervention description: Iron treatment (single injection; ~90 minutes).

Participants who conform to all eligibility criteria and have provided written informed consent will be randomised to receive either intravenous iron or placebo.

Intervention will take place at the WA Iron Centre (374 Belgravia street, Cloverdale), under the clinical care of Dr. Pradeep Jayasuriya (AHPRA: MED0001577032; Provider number: 002079AY).

Administration will be given in a registered clinic (as described above) with appropriate resuscitation facility and staff available in the event of an emergency. Participants will be administered the study medication by the unblinded person. For the drug administration the patient will have an intravenous line sited. Following this it is advised that the skin along the donor vein will be wiped using an iodine swab to help maintain the blind. The patient is to be shielded from seeing preparation of the study drug, drug administration, disconnection and removal of the intravenous line. Participants should be closely monitored as per clinic protocols throughout administration of the treatment.

1. Monofer group: 1000 mg of iron isomaltoside will be administered as an intravenous infusion (100ml n/saline) over a minimum of 15 minutes using a black infusion kit.

2. Placebo group: Normal saline will be administered as an IV infusion (100ml n/saline) over a minimum of 15 minutes using a black infusion kit.

Adverse events occurring in connection with the administration of study medication will be recorded. In the event of a patient having an allergic reaction or signs of intolerance during study drug administration, the investigator must follow local protocols. If appropriate, the investigator should complete and submit a serious adverse event (SAE) report as per trial protocol. It should be noted that adverse events will not be assessed as an outcome for the current study.

If the treatment is stopped for other reasons and the patient is willing, then treatment can be restarted where possible (as per local practice).
Intervention code [1] 318423 0
Treatment: Drugs
Comparator / control treatment
Placebo group: Normal saline will be administered as an intravenous infusion (100ml n/saline) over a minimum of 15 minutes using a black infusion kit.
Control group
Placebo

Outcomes
Primary outcome [1] 324888 0
Change in average VO2max max levels assessed by a treadmill exercise test using a validated metabolic cart.
Timepoint [1] 324888 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention
Primary outcome [2] 324896 0
Difference in change (delta) in VO2max assessed by a treadmill exercise test using a validated metabolic cart.
Timepoint [2] 324896 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention
Secondary outcome [1] 386133 0
Change in total haemoglobin mass levels as assessed using the validated optimised carbon monoxide rebreathing technique.
Timepoint [1] 386133 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention
Secondary outcome [2] 386134 0
Changes in markers of iron status (including but not limited to; Ferritin, Soluble transferrin receptor, and Hepcidin) as assessed by blood analysis.
Timepoint [2] 386134 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention
Secondary outcome [3] 386135 0
Changes in quality of life scores as assessed by the European Quality of Life- 5 Dimensions- 5 Levels Questionnaire (EQ-5D-5L).
Timepoint [3] 386135 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention
Secondary outcome [4] 386136 0
Changes in self reported mood states as assessed by the BRUMS Mood Questionnaire
Timepoint [4] 386136 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention
Secondary outcome [5] 386137 0
Changes in self reported fatigue scores as assessed by the Piper Fatigue Scale.
Timepoint [5] 386137 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention
Secondary outcome [6] 386138 0
Changes in self-efficacy levels as assessed by The Exercise Self-Efficacy Scale (ESES)
Timepoint [6] 386138 0
(i) Baseline (ii) 4 days post (iii) 4 weeks post and (iv) 3 months post intervention

Eligibility
Key inclusion criteria
Participants who are successfully screened and meet the following criteria are eligible for the study:
1. Female
2. At least 18 years of age
3. Screening haemoglobin concentration [Hb] greater than or equal to 90 g/L (9.0 g/dL) but below or equal to 130 g/L (13.0 g/dL)
4. Screening ferritin below 20 ug/L
5. Undertake at least 3 hours of regular exercise a week
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who, at the start of treatment, meet any of the following criteria are not eligible for the study:
1. Other known reason for anaemia (e.g. untreated B12 or folate deficiency or haemoglobinopathy).
2. Known history of acquired iron overload, or family history of haemochromatosis or thalassemia or TSAT (transferrin saturation) > 50%.
3. Known hypersensitivity to Monofer iron isomaltoside 1000 or its excipients.
4. Severe asthma or severe allergy (requiring hospitalisation within the last 12 months).
5. Pregnancy or lactation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
We use an online randomisation and allocation system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A commonly used independent internet-based service (www.sealedenvelope.com) will assign participants randomly to either IV iron or placebo in a 1:1 ratio. Staff involved in recruiting participants will access the system using a password and PIN code.

There will be no minimisation or stratification protocol planned as numbers in this study are small.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
N/A
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis will be performed using the Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM, Inc., New York, NY). A multivariate analysis of variance (MANOVA-treatment and time) will be used to detect any significant changes in iron status and exercise-test performance. In the event of a significant main effect, a post hoc independent t-test will be used to analyse between- group differences. ANCOVA analysis will also be used to detect any significant changes in the outcome variables (both primary and secondary). Covariates will include training load and menstrual cycle. Results will be expressed as mean and standard deviation unless otherwise stated. Significance will be considered as p < 0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2021
Actual
17/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
74
Accrual to date
20
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 306549 0
University
Name [1] 306549 0
The University of Western Australia
Country [1] 306549 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
35 Stirling Hwy, Crawley, WA, 6009
Country
Australia
Secondary sponsor category [1] 307075 0
None
Name [1] 307075 0
Address [1] 307075 0
Country [1] 307075 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306739 0
The University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 306739 0
35 Stirling Highway Crawley WA 6009 Australia
Ethics committee country [1] 306739 0
Australia
Date submitted for ethics approval [1] 306739 0
01/09/2020
Approval date [1] 306739 0
06/11/2020
Ethics approval number [1] 306739 0

Summary
Brief summary
Background: Iron is a fundamental micronutrient for numerous human processes. However, approximately one third of the population is iron deficient. A deficiency in iron stores has been linked to significant decreases in work capacity, which, if left untreated, can progress to states of anaemia, whereby there is further detriment to work capacity and quality of life. Prevalence rates of iron deficiency in female athlete populations have been calculated to be higher than that of the general population (~50%), therefore, it is common for such individuals to utilise iron supplementation strategies to maintain iron homeostasis. However, the effects of iron repletion strategies on physical performance and quality of life continue to remain latent to modern research. This study therefore aims to elucidate such effects.

Methods: The IRONWOMAN trial will utilise a double blind, randomised control design to investigate the effects of IV iron therapy on performance outcomes, quality of life and mood states in iron deficient recreational female athletes. Potential participants will be screened from the general population at universities and sporting events via the use of a female health questionnaire. Participants, who provide informed consent, will undergo familiarisation followed by baseline testing, which will involve a graded exercise test (GXT), survey completion, and a total haemoglobin mass test, using the optimised carbon monoxide rebreathing technique. Venous blood samples will be collected both prior to and post-GXT. Following this, participants will be randomly assigned to either an IV therapy group (to receive 20 mg/kg of body weight ferric derisomaltose) or a placebo group (receiving 100 ml/saline). Follow up assessments utilising the baseline test protocol will occur at 4 days post-, 4 weeks post-, and 6 months post- intervention.

Discussion: The outcomes of this research will generate the necessary empirical evidence to resolve the divergence of current literature. Indeed, results of this clinical trial will contribute towards the identification of a threshold value which elucidates the ability of IV iron therapy to improve the performance of a given individual, depending on markers of iron status. As a result, more informed decisions can be made regarding athlete iron supplementation strategies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104854 0
Mr Cory Dugan
Address 104854 0
The University of Western Australia
35 Stirling Hwy, Crawley, WA, 6009
Country 104854 0
Australia
Phone 104854 0
+61 401910790
Fax 104854 0
Email 104854 0
[email protected]
Contact person for public queries
Name 104855 0
Mr Cory Dugan
Address 104855 0
The University of Western Australia
35 Stirling Hwy, Crawley, WA, 6009
Country 104855 0
Australia
Phone 104855 0
+61 401910790
Fax 104855 0
Email 104855 0
[email protected]
Contact person for scientific queries
Name 104856 0
Mr Cory Dugan
Address 104856 0
The University of Western Australia
35 Stirling Hwy, Crawley, WA, 6009
Country 104856 0
Australia
Phone 104856 0
+61 401910790
Fax 104856 0
Email 104856 0
[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?
Final manuscript will include data related to all outcomes.
When will data be available (start and end dates)?
No later than 2 years after the collection of the final 6 month follow up assessments (no end date).
Available to whom?
On a case-by-case basis at the discretion of the principal investigator
Available for what types of analyses?
Systematic reviews and meta-analyses (inclusive of IPD-MA's)
How or where can data be obtained?
Upon request of data, by emailing the principal investigator ([email protected])


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9123Study protocol  [email protected]
9124Informed consent form  [email protected]
9125Ethical approval  [email protected]



Results publications and other study-related documents

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