NCT03559868 - Inhibition of Sterile Inflammation by Digoxin | Crick

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

45

Conditions

Inflammatory Response

Interventions

DigoxinDRUG

Participants will receive 3 mcg/Kg/day doses of oral digoxin

PlaceboOTHER

Oral placebo

DigoxinDRUG

Participants will receive 0.15 mcg/Kg/day doses of oral digoxin

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria 1. Age \>18 y ≤ 70 years 2. subjects with normal serum creatinine, normal EKG and currently not taking any medication. Exclusion criteria 1. Autoimmune liver disease (ANA \> 1/320) 2. Chronic viral hepatitis 3. Hepatocellular carcinoma 4. Complete portal vein thrombosis 5. Extrahepatic terminal disease 6. Pregnancy 7. Treatment with prednisolone or pentoxifyllin for more than 3 days prior to inclusion/start date 8. Active alcohol abuse (\>50 g/day for men and \>40 g/day for women) in the last 3 months 9. AST \> ALT and total bilirubin \> 3 mg/dl in the past 3 months 10. Liver biopsy and/or clinical picture consistent with alcoholic hepatitis 11. Lack of signed informed consent. 12. Known hypersensitivity to digoxin or other forms of digitalis, ventricular fibrillation. 13. Any significant medical conditions, any electrolyte abnormalities, over the counter medications, natural products and prescription drugs.

Locations (1)

Yale Centre of Clinical Investigation

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production

Investigators will be 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.

Time frame: after starting digoxin

Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production

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.

Time frame: 1 week after starting digoxin

Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production

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.

Time frame: 2 weeks after starting digoxin

Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production

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.

Time frame: 3 weeks after starting digoxin

Inhibition of Sterile Inflammation by Digoxin

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes