Inflammatory ResponsePhase 1NCT03559868
Inhibition of Sterile Inflammation by Digoxin
A Phase 1 study testing Digoxin in people with Inflammatory Response, run by Yale University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Response
- What is being tested?
- Digoxin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2021to 5 May 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age >18 y ≤ 70 years
- subjects with normal serum creatinine, normal EKG and currently not taking any medication.
Who cannot join
- Autoimmune liver disease (ANA > 1/320)
- Chronic viral hepatitis
- Hepatocellular carcinoma
- Complete portal vein thrombosis
- Extrahepatic terminal disease
- Pregnancy
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Centre of Clinical Investigation
New Haven, Connecticut, 06520
About this study
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.
Read the 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 how human peripheral blood immune cells change their inflammatory responses after exposure to digoxin in vitro.
- Conditions
- Inflammatory Response
- Being tested
- Digoxin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DigoxinDrug
Participants will receive 3 mcg/Kg/day doses of oral digoxin
PlaceboOther
Oral placebo
DigoxinDrug
Participants will receive 0.15 mcg/Kg/day doses of oral digoxin
| Study group | Role | What they receive |
|---|---|---|
| Digoxin 3 mcg/Kg/day | Active comparator | Patients receiving oral digoxin 3 mcg/Kg/day Receives: Drug: Digoxin |
| Digoxin 0.15 mcg | Active comparator | Patients receiving oral digoxin 0.15 mcg/Kg/day Receives: Drug: Digoxin |
| Placebo | Placebo comparator | oral placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2018
- Study start1 Mar 2021
- Primary completion5 May 2023
- Study completion5 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Inflammatory ResponseStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Wajahat Mehal, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03559868
- Sponsor's protocol ID
- 2000025289
- Other IDs
- 1U01AA026962-01
- Status last verified
- Jul 2024
- First submitted
- 6 Jun 2018
- Last updated
- 12 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibition of Sterile Inflammation by Digoxin
- ClinicalTrials.gov ID
- NCT03559868
- Acronym / sponsor ID
- 2000025289
- Conditions
- Inflammatory Response
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 5 May 2023 (actual)
- Study completion
- 5 May 2023 (actual)
- First posted
- 18 Jun 2018 (actual)
- Results
- Posted 12 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 how human peripheral blood immune cells change their inflammatory responses after exposure to digoxin in vitro.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Digoxin 3 mcg/Kg/day | Active comparator | Drug: DigoxinPatients receiving oral digoxin 3 mcg/Kg/day |
| Digoxin 0.15 mcg | Active comparator | Drug: DigoxinPatients receiving oral digoxin 0.15 mcg/Kg/day |
| Placebo | Placebo comparator | Other: Placebooral placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age >18 y ≤ 70 years
- subjects with normal serum creatinine, normal EKG and currently not taking any medication.
Key exclusion criteria (13 listed)
- Autoimmune liver disease (ANA > 1/320)
- Chronic viral hepatitis
- Hepatocellular carcinoma
- Complete portal vein thrombosis
- Extrahepatic terminal disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DigoxinParticipants will receive 3 mcg/Kg/day doses of oral digoxin | Drug | Digoxin 3 mcg/Kg/day |
| PlaceboOral placebo | Other | Placebo |
| DigoxinParticipants will receive 0.15 mcg/Kg/day doses of oral digoxin | Drug | Digoxin 0.15 mcg |
Primary outcome
Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production
Time frame: after starting digoxin
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.
Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production
Time frame: 1 week after starting digoxin
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.
Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production
Time frame: 2 weeks after starting digoxin
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.
Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production
Time frame: 3 weeks after starting digoxin
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 secondary outcome
Investigation of How Human Peripheral Blood Immune Cells Change Their Inflammatory Responses After Exposure to Digoxin in Vitro
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wajahat Mehal, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Digoxin in people with Inflammatory Response, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lower Levels of Spontaneous Reactive Oxygen Species (ROS) Production (time frame: after starting digoxin). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2024.