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Inhibition of Sterile Inflammation by Digoxin

Primary Purpose

Inflammatory Response

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Digoxin
Placebo
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Inflammatory Response

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Yale Centre of Clinical InvestigationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Digoxin 3 mcg/Kg/day

Digoxin 0.15 mcg

Placebo

Arm Description

Patients receiving oral digoxin 3 mcg/Kg/day

Patients receiving oral digoxin 0.15 mcg/Kg/day

oral placebo

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 6, 2018
Last Updated
June 23, 2023
Sponsor
Yale University
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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1. Study Identification

Unique Protocol Identification Number
NCT03559868
Brief Title
Inhibition of Sterile Inflammation by Digoxin
Official Title
Inhibition of Sterile Inflammation by Digoxin
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
July 18, 2023 (Anticipated)
Study Completion Date
July 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Response

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Digoxin 3 mcg/Kg/day
Arm Type
Active Comparator
Arm Description
Patients receiving oral digoxin 3 mcg/Kg/day
Arm Title
Digoxin 0.15 mcg
Arm Type
Active Comparator
Arm Description
Patients receiving oral digoxin 0.15 mcg/Kg/day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
oral placebo
Intervention Type
Drug
Intervention Name(s)
Digoxin
Intervention Description
Different doses of oral digoxin to test if digoxin has an effect on the immune response of peripheral blood levels (PBLs).
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Oral placebo
Primary Outcome Measure Information:
Title
Lower levels of spontaneous reactive oxygen species (ROS) production
Description
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.
Time Frame
after starting digoxin
Title
Lower levels of spontaneous reactive oxygen species (ROS) production
Description
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.
Time Frame
1 week after starting digoxin
Title
Lower levels of spontaneous reactive oxygen species (ROS) production
Description
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.
Time Frame
2 weeks after starting digoxin
Title
Lower levels of spontaneous reactive oxygen species (ROS) production
Description
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.
Time Frame
3 weeks after starting digoxin
Secondary Outcome Measure Information:
Title
Investigation of how human peripheral blood immune cells change their inflammatory responses after exposure to digoxin in vitro
Description
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.
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria Age >18 y ≤ 70 years subjects with normal serum creatinine, normal EKG and currently not taking any medication. Exclusion criteria Autoimmune liver disease (ANA > 1/320) Chronic viral hepatitis Hepatocellular carcinoma Complete portal vein thrombosis Extrahepatic terminal disease Pregnancy Treatment with prednisolone or pentoxifyllin for more than 3 days prior to inclusion/start date 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wajahat Mehal, MD
Phone
203-785-3411
Email
wajahat.mehal@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Fatima Jamshed, MD
Phone
224-213-9276
Email
fatima.jamshed@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wajahat Mehal, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale Centre of Clinical Investigation
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelly Anastasio
Phone
203-737-6845
First Name & Middle Initial & Last Name & Degree
Wajahat Z Mehal, MD, D.Phil

12. IPD Sharing Statement

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Inhibition of Sterile Inflammation by Digoxin

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