Digoxin for Congenital Erythrocytosis Due to Up-Regulated Hypoxia Sensing (NCT03433833) | Clinical Trial Compass
WithdrawnPhase 1
Digoxin for Congenital Erythrocytosis Due to Up-Regulated Hypoxia Sensing
Stopped: Study Not Funded
0Started 2019-11-10
Plain-language summary
The investigators will study digoxin to inhibit the hypoxic response in congenital erythrocytosis due to germ line mutations that result in up-regulated hypoxia sensing. These forms of congenital erythrocytosis, characterized by augmented levels of hypoxia inducible factor (HIF)-1 and HIF-2, are due to mutations of VHL (von Hippel Lindau), EGLN1 (encoding prolyl hydroxylase 2 \[PHD2\]) and EPAS1 (endothelial PAS domain-containing protein 1) (encoding HIF-2α). In addition to a high hematocrit, patients have thrombotic complications and early mortality that are not improved by phlebotomy therapy. There is no effective therapy. Digoxin, long used to treat congestive heart failure, is a potent inhibitor of the master hypoxia-inducible transcription factor, HIF-1. The study hypothesis is that pharmacologic doses and levels of digoxin will decrease hemoglobin and hematocrit, decrease need for phlebotomy, decrease the propensity to thrombosis and decrease pulmonary pressure in patients with erythrocytosis due to up-regulated hypoxic responses. The clinical trial consists of 24 weeks of digoxin therapy in patients with hypoxic response-related erythrocytosis. The complete blood count, safety, symptoms of headache and lack of energy, echocardiogram, physical performance, and plasma products and blood cell expression of HIF-1-regulated genes are the outcome variables.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria. To be eligible to participate, an individual must meet all of the following criteria:
* Have mutation of VHL (von Hippel Lindau), EGLN1 (encoding prolyl hydroxylase 2 \[PHD2\]) or EPAS1 (encoding HIF-2α) that has been associated with congenital erythrocytosis with upregulated hypoxia sensing.
* Have an up-regulated hypoxic response defined by a hemoglobin concentration of greater than 15.5 g/dL in women and 17.5 g/dL in men in association with a serum EPO concentration that is increased above the reference range or that is in the reference range but above the expected level given the presence of erythrocytosis, i.e. above the lower quartile of the range.
* Male or female, aged 18 years and older.
* For females of reproductive potential: use of highly effective contraception for 1 month prior to screening and agreement to use such a method during study participation and for an additional two weeks after the end of digoxin administration.
Exclusion criteria. An individual who meets any of the following criteria will be excluded from participation:
* Diagnosis of polycythemia vera or high oxygen affinity hemoglobinopathy.
* End stage renal disease: estimated GFR \<15 mL/min/1.73 m2 or receiving hemodialysis or peritoneal dialysis.
* Electrolyte imbalance: potassium \<3.5 mEq/L, magnesium \<1.8 mg/dL, or calcium \>10.7 mg/dL.
* Hyperthyroidism (TSH \<0.3 U/ml and T4 \>12 μg/dL) or hypothyroidism (TSH \> 6 U/ml).
* Myocarditis.
* History of hypersensitivity,…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.