There is one clinical trial.
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.
The first loss-of-function mutation of PHD2 (PHD2 P317R) was identified in a family in which heterozygotes had mild or borderline erythrocytosis. --- P317R ---
Description: Change of 1.5 g/dL or moreMeasure: Hemoglobin concentration Time: 24 weeks
Description: Change in log Epo concentration of 15% or moreMeasure: Serum EPO concentration Time: 24 weeks
Description: Change compared to baselineMeasure: Plasma concentration of PAI-1 (plasminogen activator inhibitor 1) Time: 24 weeks
Description: Change compared to baselineMeasure: Granulocyte mRNA (messenger ribonucleic acid) expression of F3 as determined by RT-PCR (reverse transcription polymerase chain reaction) Time: 24 weeks
Description: Change compared to baselineMeasure: Tricuspid regurgitation velocity determine by echocardiogram Time: 24 weeks