Please select the eligibility criteria that correspond to the clinical trial below.
Title: Physiology Study Investigating the Effects of Supplementation and Depletion of Iron on Hypoxia-related Pulmonary Hypertension
Brief Summary: The study hypothesis is that body iron levels are important in determining the increase in lung blood pressure that occurs in response to low oxygen levels. The purpose of this study is to determine whether this is true at high altitude, where oxygen levels are low.


Options:
A: Inclusion Criteria:

* Iron deficient subjects with stable chronic heart failure (CHF) (NYHA II-III) on optimal background therapy for CHF
* Reduced exercise capacity
* Reduced left ventricular ejection fraction
* At least 18 years of age and with written informed consent prior to any study specific procedures

Exclusion Criteria:

* Erythropoietin stimulating agent (ESA) use, IV iron therapy, and/or blood transfusion in previous 6 weeks prior to randomisation
* Exercise training program(s) in the 3 months prior to screening or planned in the next 6 months
* Chronic liver disease and/or elevated liver enzymes
* Vitamin B12 and/or serum folate deficiency
* Subject is not using adequate contraceptive precautions during the study
* No other significant cardiac or general disorder that would compromise participation in the study
B: Inclusion Criteria:

* In New York Heart Association (NYHA) II-III functional class due to stable symptomatic chronic heart failure (CHF)
* Left ventricular ejection fraction (LVEF) 40% or lower for patients in NYHA II and 45% or lower in NYHA III
* Screening haemoglobin (Hb) at least 9.5 g/dL but below or equal to 13.5 g/dL (average of 2 haemoglobin concentrations)
* Screening ferritin below 100 µg/L, or below 300 µg/L when transferrin saturation (TSAT) is below 20%

Exclusion Criteria:

* History of acquired iron overload.
* Known active infection, clinically significant bleeding, active malignancy.
* Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST)
* Anaemia due to reasons other than iron deficiency
* Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months).
* History of erythropoietin, i.v. or oral iron therapy, and blood transfusion in previous 12 weeks and/or such therapy planned within the next 6 months.
* Unstable angina pectoris as judged by the investigator, clinically significant uncorrected valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, poorly controlled fast atrial fibrillation or flutter, poorly controlled symptomatic brady- or tachyarrhythmias.
* Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack or stroke within the last 3 months.
* Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months.
C: Inclusion Criteria:

* Female, 18 to 45 years old,
* Serum ferritin levels \</=25 µg/L,
* Normal body Mass Index (18.5-26.5 kg/m2),
* Body weight \<80 kg,
* Signed informed consent

Exclusion Criteria:

* Anaemia (Hb \< 8.0 g/dL),
* Elevated c-reactive protein or alpha1-glycoprotein concentrations \>5.0 mg/L, \>1.0 g/L, respectively,
* Any metabolic, gastrointestinal kidney or chronic disease such as diabetes, renal failure, hepatic dysfunction, hepatitis, hypertension, cancer or cardiovascular diseases (according to the participants own statement),
* Continuous/long-term use of medication during the whole studies (except for contraceptives),
* Consumption of mineral and vitamin supplements within 2 weeks prior to 1st supplement administration,
* Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 4 months,
* Earlier participation in a study using stable iron isotopes,
* Known hypersensitivity or allergy to iron supplements,
* Women who are pregnant or breast feeding,
* Intention to become pregnant during the course of the studies,
* Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
* Known or suspected non-compliance, drug or alcohol abuse,
* Inability to follow the procedures of the studies, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Participation in another study with investigational drug within the 30 days preceding and during the present studies,
* Enrolment of the investigator, his/her family members, employees and other dependent persons
D: SLR ARM

Inclusion Criteria:

* sea level natives of lowland ancestry
* generally in good health
* detectable tricuspid regurgitation on echocardiography

Exclusion Criteria:

* any significant medical problem
* known susceptibility to high altitude pulmonary or cerebral oedema
* taking medications or iron supplements

CMS ARM

Inclusion Criteria:

* diagnosis of chronic mountain sickness
* no recent venesection therapy (within 1 year)
* detectable tricuspid regurgitation on echocardiography

Exclusion Criteria:

* any other significant medical problem

Answer: D