Trial Outcomes & Findings for Inhibition of Sterile Inflammation by Digoxin (NCT NCT03559868)

NCT ID: NCT03559868

Last Updated: 2024-07-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 45 participants
• Primary outcome timeframe: after starting digoxin
• Results posted on: 2024-07-12

Participant Flow

3 participants were consented but never started.

Participant milestones

Measure	Digoxin 3 mcg/Kg/Day Patients receiving oral digoxin 3 mcg/Kg/day Digoxin: Participants will receive 3 mcg/Kg/day doses of oral digoxin	Digoxin 0.15 mcg Patients receiving oral digoxin 0.15 mcg/Kg/day Digoxin: Participants will receive 0.15 mcg/Kg/day doses of oral digoxin	Placebo oral placebo Placebo: Oral placebo
Overall Study STARTED	14	14	14
Overall Study COMPLETED	6	6	7
Overall Study NOT COMPLETED	8	8	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Inhibition of Sterile Inflammation by Digoxin

Baseline characteristics by cohort

Measure	Digoxin 3 mcg/Kg/Day n=6 Participants Patients receiving oral digoxin 3 mcg/Kg/day Digoxin: Participants will receive 3 mcg/Kg/day doses of oral digoxin	Digoxin 0.15 mcg n=6 Participants Patients receiving oral digoxin 0.15 mcg/Kg/day Digoxin: Participants will receive 0.15 mcg/Kg/day doses of oral digoxin	Placebo n=7 Participants oral placebo Placebo: Oral placebo	Total n=19 Participants Total of all reporting groups
Age, Continuous	39.1 years STANDARD_DEVIATION 9 • n=5 Participants	31.3 years STANDARD_DEVIATION 15 • n=7 Participants	37.7 years STANDARD_DEVIATION 12 • n=5 Participants	36.1 years STANDARD_DEVIATION 12 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	19 participants n=4 Participants

PRIMARY outcome

Timeframe: after starting digoxin

Population: No data for this outcome was collected.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 1 week after starting digoxin

Population: No data for this outcome was collected.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 2 weeks after starting digoxin

Population: No data for this outcome was collected.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 3 weeks after starting digoxin

Population: No data for this outcome was collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks

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. Data presented here are the mean concentrations.

Outcome measures

Measure	Digoxin 3 mcg/Kg/Day n=6 Participants Patients receiving oral digoxin 3 mcg/Kg/day Digoxin: Participants will receive 3 mcg/Kg/day doses of oral digoxin	Digoxin 0.15 mcg n=6 Participants Patients receiving oral digoxin 0.15 mcg/Kg/day Digoxin: Participants will receive 0.15 mcg/Kg/day doses of oral digoxin	Placebo n=7 Participants oral placebo Placebo: Oral placebo
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro CCL2	697 pg/ml Standard Deviation 237	1351 pg/ml Standard Deviation 483	5790 pg/ml Standard Deviation 2442
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro CCL4	1205 pg/ml Standard Deviation 569	12180 pg/ml Standard Deviation 9763	22328 pg/ml Standard Deviation 7251
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro CCL20	894 pg/ml Standard Deviation 490	1205 pg/ml Standard Deviation 569	1761 pg/ml Standard Deviation 471
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro CXCL1	312 pg/ml Standard Deviation 232	1437 pg/ml Standard Deviation 340	2909 pg/ml Standard Deviation 725
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro CXCL10	366 pg/ml Standard Deviation 293	2472 pg/ml Standard Deviation 886	4452 pg/ml Standard Deviation 1549
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro G-CSF	35 pg/ml Standard Deviation 19	211 pg/ml Standard Deviation 80	323 pg/ml Standard Deviation 129
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro GM-CSF	42 pg/ml Standard Deviation 15	142 pg/ml Standard Deviation 39	231 pg/ml Standard Deviation 60
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro Granzyme B	182 pg/ml Standard Deviation 60	1117 pg/ml Standard Deviation 684	2734 pg/ml Standard Deviation 1582
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro IFN Alpha	26 pg/ml Standard Deviation 31	97 pg/ml Standard Deviation 61	174 pg/ml Standard Deviation 109
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro IFN Gamma	27 pg/ml Standard Deviation 9	103 pg/ml Standard Deviation 82	229 pg/ml Standard Deviation 99
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro IL-RA	1074 pg/ml Standard Deviation 290	6040 pg/ml Standard Deviation 1785	12618 pg/ml Standard Deviation 3485
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro IL-6	1064 pg/ml Standard Deviation 427	2797 pg/ml Standard Deviation 831	5006 pg/ml Standard Deviation 1171
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro PDGF AA	238 pg/ml Standard Deviation 294	1519 pg/ml Standard Deviation 773	2848 pg/ml Standard Deviation 135
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro PDGF AB/BB	128 pg/ml Standard Deviation 75	908 pg/ml Standard Deviation 539	1038 pg/ml Standard Deviation 587
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro TNF Alpha	173 pg/ml Standard Deviation 92	2786 pg/ml Standard Deviation 956	4040 pg/ml Standard Deviation 1004
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro IL-8	117 pg/ml Standard Deviation 41	306 pg/ml Standard Deviation 52	420 pg/ml Standard Deviation 24
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro Galactin 9	11977 pg/ml Standard Deviation 4287	20623 pg/ml Standard Deviation 5876	25999 pg/ml Standard Deviation 2645
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro IL10	26069 pg/ml Standard Deviation 6793	17528 pg/ml Standard Deviation 9660	2300 pg/ml Standard Deviation 2230

Adverse Events

Digoxin 3 mcg/Kg/Day

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Digoxin 0.15 mcg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Mehal Wajahat MD, DPhil

Yale University, Yale School of Medicine

Phone: 877.925.3637

Email: wajahat.mehal@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place