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Digoxin for Congenital Erythrocytosis Due to Up-Regulated Hypoxia Sensing

NCT03433833 · Status: WITHDRAWN · Phase: PHASE1 · Type: INTERVENTIONAL

Last updated 2024-09-20

No results posted yet for this study

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.

Conditions

  • Polycythemia; Familial
  • Erythrocytosis; Familial
  • VHL Gene Mutation
  • HIF-2alpha Erythrocytosis
  • PHD2 Erythrocytosis
  • Chuvash Erythrocytosis

Interventions

DRUG

Digoxin

Digoxin oral route once daily for 24 weeks.

Sponsors & Collaborators

  • University of Illinois at Chicago

    lead OTHER

Principal Investigators

  • Victor R Gordeuk, MD · University of Illinois at Chicago

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-11-10
Primary Completion
2024-04-16
Completion
2024-12-31
FDA Drug
Yes

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03433833 on ClinicalTrials.gov