HealthyNCT04227665
Identifying Biological Markers for Altitude Exposure and Use of Recombinant Human Erythropoietin (rHuEPO)
A study testing Sea level and Altitude in people with Healthy, run by University of Copenhagen at 1 site in Denmark.
Trial summary
The project represents a well powered study of the human response to altitude exposure combined with rHuEPO treatment. A total of 20 male and 20 female non-competing athletes will participate. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Sea level and Altitude
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Mar 2018to 30 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male: VO2max > 48 ml/min/kg bodyweight and 5km run < 22 min, Female: VO2max > 43ml/min/kg bodyweight and 5km run < 25 min A minimum of 2 years injury running training
Who cannot join
- Age, insufficient fitness or injury
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification of Biological Markers for Hypoxic Exposure and Use of Recombinant Human Erythropoietin
The project represents a well powered study of the human response to altitude exposure combined with rHuEPO treatment. A total of 20 male and 20 female non-competing athletes will participate. The participants will be exposed to a period of hypobaric hypoxia at 2.320 m for four weeks and a sea-level intervention period of four weeks. The participants will be blinded and randomly allocated to intra venous injection with 20 IU per kg body weight of recombinant human erythropoietin or placebo every second day for the initial three weeks of each intervention. Included subjects will be runners due to the good possibility of recruitment and conduction of training at altitude. Samples are collected weekly for four weeks prior to each intervention period, during the four week intervention and four weeks after. This approach yields a highly valuable biobank for identification of markers sensitive to initiation of rHuEPO injections as well as termination of injections.
Read the detailed description
The main hypothesis for this study is that metabolomics and proteomics methods can identify biomarkers that are sensitive to altitude exposure and recombinant human erythropoietin treatment, respectively. Secondarily, the hypothesis is that the identified biomarkers can distinguish between altitude exposure and abuse of rHuEPO.
We will include 20 Danish men and 20 Danish women aged 18-35 years. The inclusion criteria are a maximum oxygen uptake rate (VO2max) > 48 ml / kg / min for men and > 43 ml / kg / min for women. All trial participants must have > 2 years of history in regular exercise including running (> 2 times a week; > 30 min per session) and capable of performing a 5 km run in 22 min for men and 25 min for women at sea level on a level surface in dry conditions and a temperature between 10 and 20 degrees C. Furthermore, the participants must not have experienced running related injuries within the past two years.
The experimental protocol consists of two experimental periods, both of which must be performed by all participants. Both periods contain a baseline period of four weeks followed by four weeks training camp and four weeks follow up. The training camp in one period of experiments is performed at sea level while the training camp in the other period is performed at 2320 m above sea level. Each period is separated by a minimum of two months to ensure that the participants have returned to baseline values. During the two intervention periods, the participants will be transported by air and car to the destination of the respective training camp. It is expected that the participants train for 1-2 hours a day on average and that the time spent for the measurements described is ~ 5-7 hours a week.
To investigate whether the described methods can identify sensitive biomarkers for the physiological response due to rHuEPO treatment, the participants will be treated with rHuEPO.
The distribution of participants allows the following:
- 28 participants receive rHuEPO at sea level, thereby identifying biomarkers sensitive for use of rHuEPO
- 28 participants receive placebo under altitude exposure, whereby biomarkers sensitive to altitude exposure can be identified
- 12 participants receive placebo at sea level, whereby random fluctuations of the identified biomarkers can be determined.
- 12 participants receive rHuEPO under altitude exposure, whereby the identified rhuEPO biomarkers and altitude exposure can be tested for whether they can be used to separate individuals receiving rHuEPO under altitude exposure from individuals receiving placebo under altitude exposure.
- 8 participants receive placebo at sea level and altitude exposure, whereby natural and random individual fluctuations can be determined over a longer period (> 6 months). Since random individual fluctuations can be determined at n = 1, n = 8 will be sufficient to determine this.
- Conditions
- Healthy
- Being tested
- Sea level, Altitude
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sea levelOther
Sea level exposure / sea level exposure combined with microdoses of rHuEPO
AltitudeOther
Altitude exposure / altitude exposure Iron metabolism
| Study group | Role | What they receive |
|---|---|---|
| Sea level | Experimental | Sea level training camp Receives: Other: Sea level |
| Altitude | Experimental | Altitude training camp Receives: Other: Altitude |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of metabolites in urine for rHuEPO and altitude exposure
Urine is analyzed by metabolomics and the metabolites for rHuEPO and altitude are verified using an exploratory design.
More specifically, the aim is to identify the resulting metabolites from altitude exposure and treatment with rHuEPO as these are not yet known In this WADA-supported research project, the aim is to identify high sensitivity biomarkers for altitude exposure through a metabolomics methods, as 'omics' methods have previously shown promising results in other exposure contexts. However, being the first of its kind in antidoping the resulting metabolites from rHuEPO misuse and altitude have not yet been identified. Thus, an exact description of these is not possible
Measured: 5 years
Identification of human metabolites in serum for rHuEPO and altitude exposure
Human serum is analyzed by metabolomics and the metabolites for rHuEPO and altitude are verified using an exploratory design.
Measured: 5 years
Secondary outcomes (10)
Reticulocyte percentage
Reticulocyte percentage, will be measured to determine variation as a result of either 12 weeks exposure to altitude or sea-level (24 weeks in total).
Measured: Up to 24 weeks
Hemoglobin concentration
[hemoglobin] will be measured to determine variation as a result of either 12 weeks exposure to altitude or sea-level.
Measured: Up to 24 weeks
OFF-score
OFF-score (computed from reticulocyte perscentage and hemoglobin concentration), will be measured to determine variation as a result of either 12 weeks exposure to altitude or sea-level.
Measured: Up to 24 weeks
Maximal oxygen uptake (VO2max)
VO2max (ml/min) measured by incremental work load on a treadmill
Measured: Up to 24 weeks
Iron metabolism
Markers of iron metabolism such as hepcidin and erythroferrone are collected analyzed for evaluation of iron metabolism during and after a training camp at 2300m above sea level
Measured: Up to 24 weeks
Work economy
Running efficiency (%) measured by energy expenditure on a treadmill
Measured: Up to 24 weeks
Sustainable workload
Lactate threshold (mmol/L) measured on a treadmill
Measured: Up to 24 weeks
Running performance
5000m time trial performance (time) measured on a 400m running track
Measured: Up to 24 weeks
Muscle oxygenation
Muscle oxygenation measured by near-infrared spectroscopy during running on a treadmill
Measured: Up to 24 weeks
Total hemoglobin mass
Total hemoglobin mass will be measured by two-minute carbon-monoxide re-breathing to determine variation as a result of either 12 weeks exposure to altitude or sea-level.
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start1 Mar 2018
- Primary completion26 Jun 2019
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Explorative design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- World Anti-Doping Agency, German Sport University, Cologne, Universidad de Granada, Oslo University Hospital
- Responsible party
- Principal investigator, Nikolai Nordsborg, University of Copenhagen
- Investigators
- Jacob Bejder, Msc, Principal investigator, Universuty of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04227665
- Sponsor's protocol ID
- H-17036662
- Status last verified
- Apr 2026
- First submitted
- 7 May 2018
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Fully anonymous data will be shared with other researchers.
Publications
Bonne TC, Breenfeldt Andersen A, Bejder J, Loures JP, Dam C, Huertas JR, Nordsborg NB. Additive Effect of EPO and Altitude on Hemoglobin Mass But Not Peak Oxygen Uptake. Med Sci Sports Exerc. 2025 Jul 1;57(7):1366-1375. doi: 10.1249/MSS.0000000000003680. Epub 2025 Feb 17.
PubMed 39957066Arrebola-Moreno AL, Casuso RA, Bejder J, Bonne TC, Breenfeldt Andersen A, Aragon-Vela J, Nordsborg NB, Huertas JR. Does Hypoxia and Stress Erythropoiesis Compromise Cardiac Function in Healthy Adults? A Randomized Trial. Sports Med Open. 2022 Nov 5;8(1):137. doi: 10.1186/s40798-022-00531-x.
PubMed 36334130
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Biological Markers for Hypoxic Exposure and Use of Recombinant Human Erythropoietin
- ClinicalTrials.gov ID
- NCT04227665
- Acronym / sponsor ID
- H-17036662
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- World Anti-Doping Agency, German Sport University, Cologne, Universidad de Granada, Oslo University Hospital
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 26 Jun 2019 (actual)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 14 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The project represents a well powered study of the human response to altitude exposure combined with rHuEPO treatment. A total of 20 male and 20 female non-competing athletes will participate. The participants will be exposed to a period of hypobaric hypoxia at 2.320 m for four weeks and a sea-level intervention period of four weeks. The participants will be blinded and randomly allocated to intra venous injection with 20 IU per kg body weight of recombinant human erythropoietin or placebo every second day for the initial three weeks of each intervention. Included subjects will be runners due to the good possibility of recruitment and conduction of training at altitude. Samples are collected weekly for four weeks prior to each intervention period, during the four week intervention and four weeks after. This approach yields a highly valuable biobank for identification of markers sensitive to initiation of rHuEPO injections as well as termination of injections.
Detailed description
The main hypothesis for this study is that metabolomics and proteomics methods can identify biomarkers that are sensitive to altitude exposure and recombinant human erythropoietin treatment, respectively. Secondarily, the hypothesis is that the identified biomarkers can distinguish between altitude exposure and abuse of rHuEPO.
We will include 20 Danish men and 20 Danish women aged 18-35 years. The inclusion criteria are a maximum oxygen uptake rate (VO2max) > 48 ml / kg / min for men and > 43 ml / kg / min for women. All trial participants must have > 2 years of history in regular exercise including running (> 2 times a week; > 30 min per session) and capable of performing a 5 km run in 22 min for men and 25 min for women at sea level on a level surface in dry conditions and a temperature between 10 and 20 degrees C. Furthermore, the participants must not have experienced running related injuries within the past two years.
The experimental protocol consists of two experimental periods, both of which must be performed by all participants. Both periods contain a baseline period of four weeks followed by four weeks training camp and four weeks follow up. The training camp in one period of experiments is performed at sea level while the training camp in the other period is performed at 2320 m above sea level. Each period is separated by a minimum of two months to ensure that the participants have returned to baseline values. During the two intervention periods, the participants will be transported by air and car to the destination of the respective training camp. It is expected that the participants train for 1-2 hours a day on average and that the time spent for the measurements described is ~ 5-7 hours a week.
To investigate whether the described methods can identify sensitive biomarkers for the physiological response due to rHuEPO treatment, the participants will be treated with rHuEPO.
The distribution of participants allows the following:
- 28 participants receive rHuEPO at sea level, thereby identifying biomarkers sensitive for use of rHuEPO
- 28 participants receive placebo under altitude exposure, whereby biomarkers sensitive to altitude exposure can be identified
- 12 participants receive placebo at sea level, whereby random fluctuations of the identified biomarkers can be determined.
- 12 participants receive rHuEPO under altitude exposure, whereby the identified rhuEPO biomarkers and altitude exposure can be tested for whether they can be used to separate individuals receiving rHuEPO under altitude exposure from individuals receiving placebo under altitude exposure.
- 8 participants receive placebo at sea level and altitude exposure, whereby natural and random individual fluctuations can be determined over a longer period (> 6 months). Since random individual fluctuations can be determined at n = 1, n = 8 will be sufficient to determine this.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Explorative design
| Arm | Type | Receives |
|---|---|---|
| Sea level | Experimental | Other: Sea levelSea level training camp |
| Altitude | Experimental | Other: AltitudeAltitude training camp |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Male: VO2max > 48 ml/min/kg bodyweight and 5km run < 22 min, Female: VO2max > 43ml/min/kg bodyweight and 5km run < 25 min A minimum of 2 years injury running training
Key exclusion criteria (1 listed)
- Age, insufficient fitness or injury
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sea levelSea level exposure / sea level exposure combined with microdoses of rHuEPO | Other | Sea level |
| AltitudeAltitude exposure / altitude exposure Iron metabolism | Other | Altitude |
Primary outcome
Identification of metabolites in urine for rHuEPO and altitude exposure
Time frame: 5 years
Urine is analyzed by metabolomics and the metabolites for rHuEPO and altitude are verified using an exploratory design. More specifically, the aim is to identify the resulting metabolites from altitude exposure and treatment with rHuEPO as these are not yet known In this WADA-supported research project, the aim is to identify high sensitivity biomarkers for altitude exposure through a metabolomics methods, as 'omics' methods have previously shown promising results in other exposure contexts. However, being the first of its kind in antidoping the resulting metabolites from rHuEPO misuse and altitude have not yet been identified. Thus, an exact description of these is not possible
Identification of human metabolites in serum for rHuEPO and altitude exposure
Time frame: 5 years
Human serum is analyzed by metabolomics and the metabolites for rHuEPO and altitude are verified using an exploratory design.
10 secondary outcomes
Reticulocyte percentage
Time frame: Up to 24 weeks
Hemoglobin concentration
Time frame: Up to 24 weeks
OFF-score
Time frame: Up to 24 weeks
Maximal oxygen uptake (VO2max)
Time frame: Up to 24 weeks
Iron metabolism
Time frame: Up to 24 weeks
Work economy
Time frame: Up to 24 weeks
Sustainable workload
Time frame: Up to 24 weeks
Running performance
Time frame: Up to 24 weeks
Muscle oxygenation
Time frame: Up to 24 weeks
Total hemoglobin mass
Time frame: Up to 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Derived from this study: PubMed 39957066Bonne TC, Breenfeldt Andersen A, Bejder J, Loures JP, Dam C, Huertas JR, Nordsborg NB. Additive Effect of EPO and Altitude on Hemoglobin Mass But Not Peak Oxygen Uptake. Med Sci Sports Exerc. 2025 Jul 1;57(7):1366-1375. doi: 10.1249/MSS.0000000000003680. Epub 2025 Feb 17.
- Derived from this study: PubMed 36334130Arrebola-Moreno AL, Casuso RA, Bejder J, Bonne TC, Breenfeldt Andersen A, Aragon-Vela J, Nordsborg NB, Huertas JR. Does Hypoxia and Stress Erythropoiesis Compromise Cardiac Function in Healthy Adults? A Randomized Trial. Sports Med Open. 2022 Nov 5;8(1):137. doi: 10.1186/s40798-022-00531-x.
- Individual participant dataSharing planned: No. Fully anonymous data will be shared with other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacob Bejder, Msc principal investigator
Universuty of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sea level and Altitude in people with Healthy, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of metabolites in urine for rHuEPO and altitude exposure (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04227665, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.