Inhibition of Sterile Inflammation by Digoxin

NCT03559868 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 20000252891U01AA026962-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammatory Response

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  3 weeks after starting digoxin

Secondary Outcomes (1)

• Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro

  6 weeks

Study Arms (3)

Digoxin 3 mcg/Kg/day

ACTIVE COMPARATOR

Patients receiving oral digoxin 3 mcg/Kg/day

Drug: Digoxin

Digoxin 0.15 mcg

ACTIVE COMPARATOR

Patients receiving oral digoxin 0.15 mcg/Kg/day

Drug: Digoxin

Placebo

PLACEBO COMPARATOR

oral placebo

Other: Placebo

Interventions

Digoxin DRUG

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

Digoxin 3 mcg/Kg/day

Placebo OTHER

Oral placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 y ≤ 70 years
• subjects with normal serum creatinine, normal EKG and currently not taking any medication.

You may not qualify if:

• Autoimmune liver disease (ANA \> 1/320)
• Chronic viral hepatitis
• Hepatocellular carcinoma
• Complete portal vein thrombosis
• Extrahepatic terminal disease
• Pregnancy
• Active alcohol abuse (\>50 g/day for men and \>40 g/day for women) in the last 3 months
• AST \> ALT and total bilirubin \> 3 mg/dl in the past 3 months
• Liver biopsy and/or clinical picture consistent with alcoholic hepatitis
• Lack of signed informed consent.
• Known hypersensitivity to digoxin or other forms of digitalis, ventricular fibrillation.
• Any significant medical conditions, any electrolyte abnormalities, over the counter medications, natural products and prescription drugs.

Sponsors & Collaborators

• Yale University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Yale Centre of Clinical Investigation

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Interventions

Digoxin

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Results Point of Contact

• Title: Mehal Wajahat MD, DPhil
• Organization: Yale University, Yale School of Medicine

wajahat.mehal@yale.edu

877.925.3637

Study Officials

• Wajahat Mehal, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: June 18, 2018
• Study Start: March 1, 2021
• Primary Completion: May 5, 2023
• Study Completion: May 5, 2023
• Last Updated: July 12, 2024
• Results First Posted: July 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)