Pulmonary vascular tone and sensitivity to hypoxia and the influence of activation of the hypoxia-inducible factor (HIF) pathway Other
Conditions
Interventions
Participants will undergo acute and sustained hypoxia, with simultaneous transthoracic echocardiography to measure pulmonary artery systolic pressure. This will be conducted on two separate days - on
on the other a single dose of roxadustat, which is a drug that activates the hypoxia-inducible factor (HIF) pathway. These interventions will cross over such that each participant forms their own cont
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female, aged 19–60 years old 2. Willing and able to provide informed consent for participation in the study 3. Not currently taking any significant medications (to be reviewed and confirmed on a case-by-case assessment by a clinically qualified researcher) 4. Not taking the combined oral contraceptive pill. The progesterone-only pill (‘mini pill’) is acceptable. 5. No pre-existing significant medical conditions – this will be decided after a case-by-case assessment by a clinically qualified researcher
Exclusion criteria
Exclusion criteria: 1. Inability to tolerate face mask/mouthpiece/nose clip (for experimental procedure) 2. Pregnant or breastfeeding 3. Significant regular medication that could affect the result of the study (interaction with hypoxia or a possible effect on the pulmonary vasculature) and/or has a known interaction with roxadustat. 4. Previous or current significant medical problems may be an exclusion – this will be decided after a case-by-case assessment by a clinical-qualified researcher: 4.1. Pre-existing cardiorespiratory disease 4.2. Pre-existing renal or hepatic impairment 4.3. History of or current significant psychiatric illness 4.4. History of or current significant neurological condition (e.g. epilepsy) 4.5. History of or current venous thromboembolism, pulmonary embolism, or thrombophilia 4.6. Current participation in other research studies 4.7. Recent (within one month) excursions to altitude above 2500 m (with case-by-case assessment for long sojourns); recent (within 1 week) air travel over 4 hours duration 4.8. Known pre-existing anaemia and/or iron deficiency 4.9. Hypersensitivity to peanut or soya (roxadustat tablets contain traces of soya lecithin and a hypersensitivity to peanut or soya is listed as a contraindication to prescription)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Resting pulmonary vascular tone, measured as estimated pulmonary artery systolic pressure (PASP) in mmHg, using non-invasive echocardiography via tricuspid valve regurgitation. This measurement is performed when breathing normal oxygen levels. This is measured at baseline, before roxadustat/placebo, then repeated every 30 minutes for the first 2 hours, then every hour thereafter to a total time of 6 hours. 2. PASP, measured as before using echocardiography, in response to acute (20 minutes) and sustained (2 hours) hypoxia. During the 20 minutes of acute hypoxia echocardiography is continually recorded and PASP is measured every minute. 2 hours of hypoxia is then undertaken, during which measurements are not made. Then the 20-minute study is repeated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Venous blood erythropoietin concentrations before and after roxadustat, measured using blood samples taken at baseline and thereafter at 3 hours and 6 hours | — |
Countries
England, United Kingdom
Contacts
Public ContactMary Slingo
Outcome results
None listed