Inhibition of Sterile Inflammation by Digoxin

Yale University

Status and phase: Completed; Phase 1

Conditions: Inflammatory Response

Treatments: Drug: Digoxin; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03559868

1U01AA026962-01 (U.S. NIH Grant/Contract)

2000025289

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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45 participants in 3 patient groups, including a placebo group

Digoxin 3 mcg/Kg/day

Active Comparator group

Description:

Patients receiving oral digoxin 3 mcg/Kg/day

Treatment:

Drug: Digoxin

Drug: Digoxin

Digoxin 0.15 mcg

Active Comparator group

Description:

Patients receiving oral digoxin 0.15 mcg/Kg/day

Treatment:

Drug: Digoxin

Drug: Digoxin

Placebo

Placebo Comparator group

Description:

oral placebo

Treatment:

Other: Placebo