Inhibition of Sterile Inflammation by Digoxin

Inflammatory Response Clinical Trial

Official title:

Inhibition of Sterile Inflammation by Digoxin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03559868
• Other study ID #: 2000025289
• Secondary ID: 1U01AA026962-01
• Status: Completed
• Phase: Phase 1
• Start date: March 1, 2021
• Est. completion date: May 5, 2023

Study information

• Verified date: May 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 5, 2023
• Est. primary completion date: May 5, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Inflammation
• Inflammatory Response

Intervention

Drug:
• Digoxin
Participants will receive either 3 or 0.15 mcg/Kg/day doses of oral digoxin

Other:
• Placebo
Oral placebo

Locations

Country	Name	City	State
United States	Yale Centre of Clinical Investigation	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lower levels of spontaneous reactive oxygen species (ROS) production	We will be taking 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.	after starting digoxin
Primary	Lower levels of spontaneous reactive oxygen species (ROS) production	We will be taking 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.	1 week after starting digoxin
Primary	Lower levels of spontaneous reactive oxygen species (ROS) production	We will be taking 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.	2 weeks after starting digoxin
Primary	Lower levels of spontaneous reactive oxygen species (ROS) production	We will be taking 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.	3 weeks after starting digoxin
Secondary	Investigation of how human peripheral blood immune cells change their inflammatory responses after exposure to digoxin in vitro	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.	6 weeks