Inhibition of Sterile Inflammation by Digoxin

Phase 1

Completed

• Conditions: Inflammatory Response
• Interventions: Other: Placebo; Drug: Digoxin

• Registration Number: NCT03559868
• Lead Sponsor: Yale University

Brief Summary

To investigate the effect of digoxin on pyruvate kinase isoform 2 (PKM2) binding to pro-inflammatory loci and innate immune inflammatory responses in the peripheral blood in healthy subjects.

Detailed Description

To investigate the effect of orally administered digoxin on innate immune inflammatory responses in the peripheral blood of healthy subjects. We hypothesize the reduction in innate immune inflammatory responses will be expected in the peripheral blood with the effect of oral digoxin.

To investigation how human peripheral blood immune cells change their inflammatory responses after exposure to digoxin in vitro.

Study Timeline

• Study First Submitted: 2018-06-06
• Study First Submitted QC: 2018-06-06
• Study First Posted: 2018-06-18
• Study Start: 2021-03-01
• Primary Completion: 2023-05-05
• Study Completion: 2023-05-05
• Disposition First Posted: 2024-02-16
• Disposition First Submitted: 2024-04-30
• Results First Submitted: 2024-06-13
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-10
• Last Update Submitted: 2024-07-10
• Results First Posted: 2024-07-12
• Last Update Posted: 2024-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	oral placebo
Digoxin 0.15 mcg	Digoxin	Patients receiving oral digoxin 0.15 mcg/Kg/day
Digoxin 3 mcg/Kg/day	Digoxin	Patients receiving oral digoxin 3 mcg/Kg/day

Primary Outcome Measures

Name	Time	Method
Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production	3 weeks after starting digoxin	Investigators will take neutrophils (PMN's) from the blood and seeing if the patients on digoxin have lower levels of spontaneous reactive oxygen species (ROS) production. This will be determined as a greater than 25% reduction in ROS compared to individuals not taking digoxin. The serum digoxin levels are just being done per usual guidelines to make sure that supratherapeutic levels of digoxin are not reached.

Secondary Outcome Measures

Name	Time	Method
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro	6 weeks	Blood (25ml) will be obtained from healthy blood donors at one time. Human peripheral monocytes will be isolated using Polymorphprep™ density sedimentation according to the manufacturer's instructions. Data presented here are the mean concentrations.

Trial Locations

Locations (1)

Yale Centre of Clinical Investigation; 🇺🇸 New Haven, Connecticut, United States