Identification of Biological Markers for Hypoxic Exposure and Use of Recombinant Human Erythropoietin
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Identification of metabolites in urine for rHuEPO and altitude exposure
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •Age, insufficient fitness or injury
结局指标
主要结局
Identification of metabolites in urine for rHuEPO and altitude exposure
时间窗: 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
时间窗: 5 years
Human serum is analyzed by metabolomics and the metabolites for rHuEPO and altitude are verified using an exploratory design.
次要结局
- Running performance(Up to 24 weeks)
- Reticulocyte percentage(Up to 24 weeks)
- Hemoglobin concentration(Up to 24 weeks)
- OFF-score(Up to 24 weeks)
- Maximal oxygen uptake (VO2max)(Up to 24 weeks)
- Iron metabolism(Up to 24 weeks)
- Work economy(Up to 24 weeks)
- Sustainable workload(Up to 24 weeks)
- Muscle oxygenation(Up to 24 weeks)
- Total hemoglobin mass(Up to 24 weeks)
研究者
Nikolai Nordsborg
Associate Professor
University of Copenhagen