Identifying Biological Markers for Altitude Exposure and Use of Recombinant Human Erythropoietin (rHuEPO)

Healthy Clinical Trial

Official title:

Identification of Biological Markers for Hypoxic Exposure and Use of Recombinant Human Erythropoietin

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04227665
• Other study ID #: H-17036662
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 1, 2018
• Est. completion date: May 30, 2025

Study information

• Verified date: November 2023
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: May 30, 2025
• Est. primary completion date: June 26, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Age, insufficient fitness or injury

Related Conditions & MeSH terms

• Healthy

Intervention

Other:
• Sea level
Sea level exposure / sea level exposure combined with microdoses of rHuEPO
• Altitude
Altitude exposure / altitude exposure Iron metabolism

Locations

Country	Name	City	State
Denmark	University of Copenhagen	Copenhagen	Copenhagen Ø

Sponsors (5)

Lead Sponsor	Collaborator
University of Copenhagen	German Sport University, Cologne, Oslo University Hospital, Universidad de Granada, World Anti-doping Agency

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	5 years
Primary	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.	5 years
Secondary	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).	Up to 24 weeks
Secondary	Hemoglobin concentration	[hemoglobin] will be measured to determine variation as a result of either 12 weeks exposure to altitude or sea-level.	Up to 24 weeks
Secondary	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.	Up to 24 weeks
Secondary	Maximal oxygen uptake (VO2max)	VO2max (ml/min) measured by incremental work load on a treadmill	Up to 24 weeks
Secondary	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	Up to 24 weeks
Secondary	Work economy	Running efficiency (%) measured by energy expenditure on a treadmill	Up to 24 weeks
Secondary	Sustainable workload	Lactate threshold (mmol/L) measured on a treadmill	Up to 24 weeks
Secondary	Running performance	5000m time trial performance (time) measured on a 400m running track	Up to 24 weeks
Secondary	Muscle oxygenation	Muscle oxygenation measured by near-infrared spectroscopy during running on a treadmill	Up to 24 weeks
Secondary	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.	Up to 24 weeks