Unravelling Energy Issues Underpinning Low Energy Availability in High Performance Athletes

NCT ID: NCT07026175

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2027-06-30

Brief Summary

The goal of this clinical trial is to understand how the body responds to short-term, severe low energy availability (LEA) in healthy, weight-bearing endurance athletes aged 18-45 years old. LEA describes a mismatch between an individual's dietary energy intake and the energy cost of their commitments for training and competition. The main questions this trial aims to answer are:

1. What effect does short-term, severe LEA have on sleeping metabolic rate?

2. What effect does short-term, severe LEA have on other body systems identified within the Relative Energy Deficiency in Sport (REDs) Health and Performance Conceptual models?

Researchers will compare a control trial with both a LEA trial achieved through diet restriction and a LEA trial achieved through increased exercise to see if there are differences in the body's response.

Participants will complete three 6-day trials, a minimum of 3-weeks apart, involving:

• Prescribed diet (all food provided)
• Prescribed running and/or cycling exercise
• Two visits to ACU Fitzroy campus for blood tests and exercise testing
• 50 hour stay (two nights and two days) in the ACU metabolic chamber

Detailed Description

The study will involve a three-sequence crossover design, with participants undertaking a control trial first, involving energy availability of 40 kcal/kg fat free mass (FFM) and a 15 kcal/kg FFM exercise energy expenditure (EEE) as baseline training volume, before a counterbalanced allocation to low energy availability via dietary restriction (LEADIET) or low energy availability via increased exercise energy expenditure (LEAEX). This design will allow further screening of Relative Energy Deficiency in Sport (REDs) risk, identify participants who are likely to be unable to fulfil the exercise commitments of LEAEX and avoid the unknown carryover effects of two consecutive low energy availability (LEA) trials on the subsequent control trial, as would occur in some participants with a fully counterbalanced treatment allocation.

Baseline testing (body composition/bone mineral density via DXA, aerobic capacity, LEA hormone blood panel, vitamin D, resting metabolic rate, REDs screening via REDs-CAT2) will be undertaken to confirm inclusion and develop individualised diet and training plans. Thereafter, participants will undertake a 6-day supervised exposure to energy availability of ~40 kcal/kg FFM/d, involving supplied meals and prescribed daily running/race walking. For female participants, trials will commence within days 1-5 of the menstrual cycle, to ensure that all testing occurs in the same (follicular) phase. A minimum 3-week washout period will occur between trials, with participants being guided to return to habitual training and dietary habits. Trials 2 and 3 will consist of exposure to severe LEA (15 kcal/kg FFM/d), which is achieved either by superimposing restricted energy intake (EI) or increased (doubled) EEE on the previous training plan.

Diet plans and food provision will be managed by experienced sports dietitians to incorporate individual preferences and intolerances. While participants are free-living at the start of each trial week, food drops will be undertaken to check well-being and compliance to the diet/ training intervention. The final 2 days of residence at ACU facilities (medical unit and metabolic chamber) will allow more comprehensive data collection. Individual protocols (described briefly below) have been previously developed by our group and collaborators. Together, they will investigate within and between trial changes in metrics representing the range of body systems that have been identified at risk of perturbations due to LEA within the REDs Conceptual Health and Performance Models.

Summary of the protocols completed in this study:

1. VO2 max: Running protocol: Measured once at screening visit (and potentially remeasured if participant trials are spaced >3 months apart and aerobic fitness requires rechecking)

2. Resting Metabolic Rate: Outpatient protocol via Parvo metabolic cart: Measured once in baseline testing to enable calculation of EA components for intervention

3. DXA: total body composition: Measured once at screening visit to enable calculation of EA components for intervention, and twice in each trial (Day 1 and Day 5)

4. DXA: bone mineral density (Hip and Spine): Measured once at screening visit

5. Cognitive tests: 5-minute psychomotor vigilance test (PVT) & 3-minute Simon Squared, delivered via Inquisit software (screening visit, then Day 1 and Day 6)

6. RESTQ-76: questionnaire of overall wellbeing (Day 6)

7. Diet feedback questionnaire (Day 6)

8. Oura Ring: sleep characteristics, resting heart rate (HR), total energy expenditure (EE), basal body temperature, HR variability (HRV) (throughout each trial)

9. Somfit: sleep architecture (Night of Days 3, 4, and 5)

10. Training capacity: Garmin-derived HR and EE, rate of perceived exertion (RPE, throughout trial), metabolic, physiological and perceptual responses during standardised running test (Day 5)

11. Dietary iron absorption and incorporation: Intake of stable isotope (3.8mg, Fe57 as ferrous sulphate) (evening of Day 4), with 8 blood samples collected from 0-480 min post dose to assess iron absorption. A further blood sample taken after 28 days will measure incorporation into red blood cells to assess functional iron availability

12. Venepuncture/Venous cannulation: Total blood volume per trial = 140 ml for:

• LEA panel: testosterone, estrogen, progesterone, IGF-1, T3, leptin, iron status, lipids, glucose/insulin (screening visit, Day 1 and Day 5)
• Hormone pulsatility: 8 h @15 min collection of Luteinising Hormone, Growth Hormone, Cortisol (overnight Day 4)
• Appetite peptides: Leptin, Active Ghrelin, PP, GLP-1, PYY (Day 5)
• Immune response: IL-6, mitochondrial respiration, reactive oxygen species emission, and protein expression in peripheral blood mononuclear cells (PBMCs), circulating leukocyte type distribution and mobilisation, circulating cell-free DNA (Day 5)
• Bone turnover: CTX-1 and P1NP (Day 5)
• Iron absorption and response: plasma iron-isotope appearance (overnight Day 4), Hepcidin (Day 5)

13. Exercise metabolism: blood lactate, glucose (finger prick collection, Day 5 exercise)

14. Gut comfort: Standardised GI questionnaire pre- and post-exercise (Day 5 exercise)

15. Protein turnover: Consumption of stable isotopes of 15N-glycine and D3-3-methyl-histidine (Day 4), with a baseline urine sample, and serial timed samples (Days 5 and 6) will allow determination of whole-body protein turnover (measured as 15N-Alanine), and muscle proteolysis

16. Bone breakdown: Measurement of Ca isotope abundance in urine (on waking urine sample on Day 1 and 24-hour urine sample on Day 5/6 in metabolic chamber) will allow assessment of bone breakdown (periods of greater bone breakdown: formation will see greater abundance of lighter isotopes).

17. Metabolic chamber: 24 h energy expenditure, sleeping metabolic rate, basal metabolic rate, EEE (Day 5/6 in metabolic chamber)

18. Blood glucose monitoring: blood glucose monitoring, using continuous glucose monitors (Freestyle Libre Pro iQ) (from Day 1 through to end of Day 6)

Conditions

Relative Energy Deficiency in Sport

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Control Trial

A 6-day control trial. All participants will commence with this trial involving an energy availability of 40 kcal/kg fat-free mass (FFM). Energy intake will be 55 kcal/kg FFM/d and exercise energy expenditure will be 15 kcal/kg FFM/d. This will be followed by a minimum 3-week washout period where the participant will be advised to return to their routine diet and exercise.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Low Energy Availability - Diet

A 6-day severe low energy availability (LEA, 15kcal/kg FFM/d) trial, achieved by superimposing restricted energy intake on the HEA trial. Energy intake will be 30 kcal/kg FFM/d and exercise energy expenditure will be 15 kcal/kg FFM/d. This will be followed by a minimum 3-week washout period where the participant will be advised to return to their routine diet and exercise.

Group Type: EXPERIMENTAL

Diet-induced low energy availability

Intervention Type: OTHER

6-days of severe low energy availability (LEA, 15kcal/kg FFM/d), achieved by superimposing restricted energy intake on the control trial.

Low Energy Availability - Exercise

A 6-day severe low energy availability (LEA, 15kcal/kg FFM/d) trial, achieved by superimposing increased exercise energy expenditure on the HEA trial. Energy intake will be 45 kcal/kg FFM/d and exercise energy expenditure will be 30 kcal/kg FFM/d. This will be followed by a minimum 3-week washout period where the participant will be advised to return to their routine diet and exercise.

Group Type: EXPERIMENTAL

Exercise-induced low energy availability

Intervention Type: OTHER

6-days of severe low energy availability (LEA, 15kcal/kg FFM/d), achieved by superimposing increased exercise energy expenditure on the control trial.

Interventions

Diet-induced low energy availability

6-days of severe low energy availability (LEA, 15kcal/kg FFM/d), achieved by superimposing restricted energy intake on the control trial.

Intervention Type: OTHER

Exercise-induced low energy availability

6-days of severe low energy availability (LEA, 15kcal/kg FFM/d), achieved by superimposing increased exercise energy expenditure on the control trial.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 18-45 years old
• Well trained weight-bearing athlete (tier 2-4 1)
• Perform ~45km per week of weight-bearing endurance training, and able to undertake the prescribed exercise in each trial condition
• Pass the ESSA pre-exercise screening tool and/or obtain GP clearance to exercise

Exclusion Criteria

• Assessment of red status on the REDs Clinical Assessment Tool
• Unable to attend ACU in Fitzroy, Victoria, for the 6 study visits for completion of the study protocol
• Pregnancy
• Use of hormonal contraceptive with the previous 3 months
• Onset of peri/menopause

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Wu Tsai Human Performance Alliance

UNKNOWN

Sponsor Role: collaborator

Australian Catholic University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Louise M Burke, PhD

Role: PRINCIPAL_INVESTIGATOR

Australian Catholic University

Locations

Australian Catholic University

Fitzroy, Victoria, Australia

Site Status: RECRUITING

Countries

Australia

Central Contacts

Louise M Burke, PhD

Role: CONTACT

louise.burke@acu.edu.au

+61 4 22 635 869

Margot A Rogers, PhD

Role: CONTACT

margot.rogers@acu.edu.au

+61 4 47 958 373

Facility Contacts

Margot A Rogers, PhD

Role: primary

margot.rogers@acu.edu.au

+61 447 958 373

References

Burke LM, Ackerman KE, Heikura IA, Hackney AC, Stellingwerff T. Mapping the complexities of Relative Energy Deficiency in Sport (REDs): development of a physiological model by a subgroup of the International Olympic Committee (IOC) Consensus on REDs. Br J Sports Med. 2023 Sep;57(17):1098-1108. doi: 10.1136/bjsports-2023-107335.

Reference Type: BACKGROUND

PMID: 37752007 (View on PubMed)

Mountjoy M, Ackerman KE, Bailey DM, Burke LM, Constantini N, Hackney AC, Heikura IA, Melin A, Pensgaard AM, Stellingwerff T, Sundgot-Borgen JK, Torstveit MK, Jacobsen AU, Verhagen E, Budgett R, Engebretsen L, Erdener U. 2023 International Olympic Committee's (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs). Br J Sports Med. 2023 Sep;57(17):1073-1097. doi: 10.1136/bjsports-2023-106994.

Reference Type: BACKGROUND

PMID: 37752011 (View on PubMed)

Loucks AB, Kiens B, Wright HH. Energy availability in athletes. J Sports Sci. 2011;29 Suppl 1:S7-15. doi: 10.1080/02640414.2011.588958. Epub 2011 Jul 28.

Reference Type: BACKGROUND

PMID: 21793767 (View on PubMed)

Other Identifiers

2025-4078HC

Identifier Type: -

Identifier Source: org_study_id