- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04458662
Iron and Muscular Damage: FEmale Metabolism and Menstrual Cycle During Exercise (IronFEMME)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Madrid, Spain, 28040
- Laboratorio de Fisiología Del Esfuerzo. Facultad de Ciencias de La Actividad Física Y Del Deporte. Universidad Politécnica de Madrid.
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Participants were required to meet the following criteria:
- Healthy adult females between 18 and 40 years old for eumerroheic and oral contraceptive groups or under 60 years old for postmenopausal women.
- Presenting with healthy iron parameters (serum ferritin >20μg/l, haemoglobin >115 μg/l and transferrin saturation >16%).
- Performing endurance training between 5 and 12 h per week (study I) or experienced in resistance training performing at least 1 h session two times per week during a minimum of a year (study II).
Exclusion Criteria:
The exclusion criteria included:
- Irregular menstrual cycles.
- Any existing disease and/or metabolic or hormonal disorder.
- Any musculoskeletal injury in the last six months prior to the beginning of the project.
- Any surgery interventions (e.g. ovariectomy) or other medical conditions that would be exacerbated by an eccentric resistance exercise protocol.
- Regular use of medication or dietary supplements that could affect the results (e.g. nonsteroidal anti-inflammatory drugs).
- Taking medication that alters vascular function (e.g. tricyclic antidepressants, α-blockers, β-blockers, etc.).
- Pregnancies in the year preceding.
- Smoking.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Eumenorrheic women
The project consisted on two sections carrying out at the same time: Iron physiology (Study I) and Muscle damage (Study II). For the study I, the exercise protocol consisted on an interval running test. 5 min warm-up at 60% of the vVO2peak followed by 8 bouts of 3 min at 85% of the vVO2peak with 90 secs recovery at 30% of the vVO2peak between bouts. Finally, a 5 min cool down was performed at 30% of the vVO2peak. The study II protocol was based on an eccentric-based resistance exercise protocol consisted on 10 sets of 10 reps of plate-loaded parallel back squats at 60% of their previously calculated 1RM with 2 mins recoveries between sets. In both studies, eumenorrheic participants were evaluated at three specific moments of the menstrual cycle: Early-follicular phase (EFP), late-follicular phase (LFP) and mid-luteal phase (MLP); |
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Oral contraceptive users
The project consisted on two sections carrying out at the same time: Iron physiology (Study I) and Muscle damage (Study II). For the study I, the exercise protocol consisted on an interval running test. 5 min warm-up at 60% of the vVO2peak followed by 8 bouts of 3 min at 85% of the vVO2peak with 90 secs recovery at 30% of the vVO2peak between bouts. Finally, a 5 min cool down was performed at 30% of the vVO2peak. The study II protocol was based on an eccentric-based resistance exercise protocol consisted on 10 sets of 10 reps of plate-loaded parallel back squats at 60% of their previously calculated 1RM with 2 mins recoveries between sets. Oral contraceptive users performed the trial at two moments: Withdrawal phase (WP) and active pill phase (APP). |
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Postmenopausal women
he project consisted on two sections carrying out at the same time: Iron physiology (Study I) and Muscle damage (Study II). For the study I, the exercise protocol consisted on an interval running test. 5 min warm-up at 60% of the vVO2peak followed by 8 bouts of 3 min at 85% of the vVO2peak with 90 secs recovery at 30% of the vVO2peak between bouts. Finally, a 5 min cool down was performed at 30% of the vVO2peak. The study II protocol was based on an eccentric-based resistance exercise protocol consisted on 10 sets of 10 reps of plate-loaded parallel back squats at 60% of their previously calculated 1RM with 2 mins recoveries between sets. Postmenopausal women were tested only once, since their hormonal status does not fluctuate. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hepcidin
Time Frame: pre-exercise
|
Hepcidin is a protein that in humans is encoded by the HAMP gene.
Hepcidin is a key regulator of the entry of iron into the circulation in mammals
|
pre-exercise
|
Hepcidin
Time Frame: 0 hours post-exercise
|
Hepcidin is a protein that in humans is encoded by the HAMP gene.
Hepcidin is a key regulator of the entry of iron into the circulation in mammals
|
0 hours post-exercise
|
Hepcidin
Time Frame: 3 hours post-exercise
|
Hepcidin is a protein that in humans is encoded by the HAMP gene.
Hepcidin is a key regulator of the entry of iron into the circulation in mammals
|
3 hours post-exercise
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Hepcidin
Time Frame: 24 hours post-exercise
|
Hepcidin is a protein that in humans is encoded by the HAMP gene.
Hepcidin is a key regulator of the entry of iron into the circulation in mammals
|
24 hours post-exercise
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Creatine kinase
Time Frame: pre-exercise
|
It is an enzyme that helps regulate the concentration of adenosine triphosphate within a cell.
To do so, creatine kinase catalyzes the movement of a phosphate group from ATP to creatine, forming phosphocreatine.
This molecules stores the phosphate group in a stable form, acting as an energy reservoir in cells.
|
pre-exercise
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Creatine kinase
Time Frame: 2 hours post-exercise
|
It is an enzyme that helps regulate the concentration of adenosine triphosphate within a cell.
To do so, creatine kinase catalyzes the movement of a phosphate group from ATP to creatine, forming phosphocreatine.
This molecules stores the phosphate group in a stable form, acting as an energy reservoir in cells.
|
2 hours post-exercise
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Creatine kinase
Time Frame: 24 hours post-exercise
|
It is an enzyme that helps regulate the concentration of adenosine triphosphate within a cell.
To do so, creatine kinase catalyzes the movement of a phosphate group from ATP to creatine, forming phosphocreatine.
This molecules stores the phosphate group in a stable form, acting as an energy reservoir in cells.
|
24 hours post-exercise
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Creatine kinase
Time Frame: 48 hours post-exercise
|
It is an enzyme that helps regulate the concentration of adenosine triphosphate within a cell.
To do so, creatine kinase catalyzes the movement of a phosphate group from ATP to creatine, forming phosphocreatine.
This molecules stores the phosphate group in a stable form, acting as an energy reservoir in cells.
|
48 hours post-exercise
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Iron
Time Frame: pre-exercise
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pre-exercise
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Iron
Time Frame: 0 hours post-exercise
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0 hours post-exercise
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Iron
Time Frame: 3 hours post-exercise
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3 hours post-exercise
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Iron
Time Frame: 24 hours post-exercise
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24 hours post-exercise
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Transferrin
Time Frame: pre-exercise
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pre-exercise
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Transferrin
Time Frame: 0 hours post-exercise
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0 hours post-exercise
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Transferrin
Time Frame: 3 hours post-exercise
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3 hours post-exercise
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Transferrin
Time Frame: 24 hours post-exercise
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24 hours post-exercise
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Ferritin
Time Frame: pre-exercise
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pre-exercise
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Ferritin
Time Frame: 0 hours post-exercise
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0 hours post-exercise
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Ferritin
Time Frame: 3 hours post-exercise
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3 hours post-exercise
|
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Ferritin
Time Frame: 24 hours post-exercise
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24 hours post-exercise
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Mioglobin
Time Frame: pre-exercise
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pre-exercise
|
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Mioglobin
Time Frame: 2 hours post-exercise
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2 hours post-exercise
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Mioglobin
Time Frame: 24 hours post-exercise
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24 hours post-exercise
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Mioglobin
Time Frame: 48 hours post-exercise
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48 hours post-exercise
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LDH
Time Frame: pre-exercise
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Lactate deshidrogenase
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pre-exercise
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LDH
Time Frame: 2 hours post-exercise
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Lactate deshidrogenase
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2 hours post-exercise
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LDH
Time Frame: 24 hours post-exercise
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Lactate deshidrogenase
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24 hours post-exercise
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LDH
Time Frame: 48 hours post-exercise
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Lactate deshidrogenase
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48 hours post-exercise
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TNF-alfa
Time Frame: pre-exercise
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pre-exercise
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TNF-alfa
Time Frame: 2 hours post-exercise
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2 hours post-exercise
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TNF-alfa
Time Frame: 24 hours post-exercise
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24 hours post-exercise
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TNF-alfa
Time Frame: 48 hours post-exercise
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48 hours post-exercise
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Interleukin-6
Time Frame: pre-exercise
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pre-exercise
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Interleukin-6
Time Frame: 0 hours post-exercise
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0 hours post-exercise
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Interleukin-6
Time Frame: 2 hours post-exercise
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2 hours post-exercise
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Interleukin-6
Time Frame: 24 hours post-exercise
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24 hours post-exercise
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Interleukin-6
Time Frame: 48 hours post-exercise
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48 hours post-exercise
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CRP
Time Frame: pre-exercise
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C-reactive protein
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pre-exercise
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CRP
Time Frame: 0 hours post-exercise
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C-reactive protein
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0 hours post-exercise
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CRP
Time Frame: 2 hours post-exercise
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C-reactive protein
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2 hours post-exercise
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CRP
Time Frame: 24 hours post-exercise
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C-reactive protein
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24 hours post-exercise
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CRP
Time Frame: 48 hours post-exercise
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C-reactive protein
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48 hours post-exercise
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: Ana Belén Peinado, LFE Research Group. Universidad Politécnica de Madrid
Publications and helpful links
General Publications
- Lehtihet M, Bonde Y, Beckman L, Berinder K, Hoybye C, Rudling M, Sloan JH, Konrad RJ, Angelin B. Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans. PLoS One. 2016 Feb 11;11(2):e0148802. doi: 10.1371/journal.pone.0148802. eCollection 2016.
- Hou Y, Zhang S, Wang L, Li J, Qu G, He J, Rong H, Ji H, Liu S. Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. Gene. 2012 Dec 15;511(2):398-403. doi: 10.1016/j.gene.2012.09.060. Epub 2012 Oct 3.
- Ikeda Y, Tajima S, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Tamaki T. Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes. PLoS One. 2012;7(7):e40465. doi: 10.1371/journal.pone.0040465. Epub 2012 Jul 11.
- Li X, Rhee DK, Malhotra R, Mayeur C, Hurst LA, Ager E, Shelton G, Kramer Y, McCulloh D, Keefe D, Bloch KD, Bloch DB, Peterson RT. Progesterone receptor membrane component-1 regulates hepcidin biosynthesis. J Clin Invest. 2016 Jan;126(1):389-401. doi: 10.1172/JCI83831. Epub 2015 Dec 14.
- Yang Q, Jian J, Katz S, Abramson SB, Huang X. 17beta-Estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site. Endocrinology. 2012 Jul;153(7):3170-8. doi: 10.1210/en.2011-2045. Epub 2012 Apr 25.
- Thompson B, Almarjawi A, Sculley D, Janse de Jonge X. The Effect of the Menstrual Cycle and Oral Contraceptives on Acute Responses and Chronic Adaptations to Resistance Training: A Systematic Review of the Literature. Sports Med. 2020 Jan;50(1):171-185. doi: 10.1007/s40279-019-01219-1.
- McClung JP. Iron status and the female athlete. J Trace Elem Med Biol. 2012 Jun;26(2-3):124-6. doi: 10.1016/j.jtemb.2012.03.006. Epub 2012 May 7.
- Kendall B, Eston R. Exercise-induced muscle damage and the potential protective role of estrogen. Sports Med. 2002;32(2):103-23. doi: 10.2165/00007256-200232020-00003.
- Tiidus PM, Lowe DA, Brown M. Estrogen replacement and skeletal muscle: mechanisms and population health. J Appl Physiol (1985). 2013 Sep 1;115(5):569-78. doi: 10.1152/japplphysiol.00629.2013. Epub 2013 Jul 18.
- Sim M, Dawson B, Landers G, Swinkels DW, Tjalsma H, Yeap BB, Trinder D, Peeling P. Oral contraception does not alter typical post-exercise interleukin-6 and hepcidin levels in females. J Sci Med Sport. 2015 Jan;18(1):8-12. doi: 10.1016/j.jsams.2013.11.008. Epub 2013 Nov 28.
- Sipaviciene S, Daniuseviciute L, Kliziene I, Kamandulis S, Skurvydas A. Effects of estrogen fluctuation during the menstrual cycle on the response to stretch-shortening exercise in females. Biomed Res Int. 2013;2013:243572. doi: 10.1155/2013/243572. Epub 2013 Sep 12.
- Janse DE Jonge X, Thompson B, Han A. Methodological Recommendations for Menstrual Cycle Research in Sports and Exercise. Med Sci Sports Exerc. 2019 Dec;51(12):2610-2617. doi: 10.1249/MSS.0000000000002073.
- Romero-Parra N, Barba-Moreno L, Rael B, Alfaro-Magallanes VM, Cupeiro R, Diaz AE, Calderon FJ, Peinado AB. Influence of the Menstrual Cycle on Blood Markers of Muscle Damage and Inflammation Following Eccentric Exercise. Int J Environ Res Public Health. 2020 Mar 2;17(5):1618. doi: 10.3390/ijerph17051618.
- Alfaro-Magallanes VM, Barba-Moreno L, Romero-Parra N, Rael B, Benito PJ, Swinkels DW, Laarakkers CM, Diaz AE, Peinado AB; IronFEMME Study Group. Menstrual cycle affects iron homeostasis and hepcidin following interval running exercise in endurance-trained women. Eur J Appl Physiol. 2022 Dec;122(12):2683-2694. doi: 10.1007/s00421-022-05048-5. Epub 2022 Sep 21. Erratum In: Eur J Appl Physiol. 2022 Oct 12;:
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DEP2016-75387-P
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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