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NASHPhase 2CODINNCT06588699

Digoxin In NASH (CODIN)

A Phase 2 study testing Digoxin in people with NASH and NAFLD, run by Yale University at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Nonalcoholic steatohepatitis (NASH) is a severe subtype of nonalcoholic fatty liver disease (NAFLD) which affects 1 in 3 Americans. The mainstay of treatment for NASH, which was recently renamed metabolic associated steatohepatitis (MASH), involves lifestyle interventions to promote weight loss and to treat… Read more about this study

Who is it for?
Ages 18 to 75 years
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
144 participants
Where
2 sitesUnited States
Study dates
5 Jun 2025to Jan 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Stable body weight (≤ 5% self-reported change in body weight) in the 30 days prior to screening
  • Biopsy-confirmed non-alcoholic steatohepatitis (NASH) as defined by the NASH clinical research network (NASH CRN) histological scoring system, with non-alcoholic fatty liver disease score (NAS) ≥4 and with a score ≥1 for each of the three components (steatosis, hepatocellular ballooning, and lobular inflammation) on a liver biopsy performed within 6 months of screening
  • Histological fibrosis stage 2 or 3 based on pathologist evaluation of a liver biopsy performed up to 6 months before screening
  • Agrees to have a liver biopsy performed to assess baseline histology if one has not been performed up to 6 months before screening, and at 24 weeks after randomization Exclusion Criteria
  • Liver-related:
  • Documented causes of chronic liver disease other than NASH
Show all 38Show fewer
  • History or clinical evidence of cirrhosis or portal hypertension
  • History of positive HBsAg, positive anti-HIV, positive HCV-RNA
  • AST or ALT > 5 times upper limit of normal (ULN) at screening
  • Total bilirubin > 1.5 mg/dL at screening unless conjugated bilirubin is < 1.5 × ULN
  • International normalized ratio (INR) > 1.3 at screening
  • Known or suspected alcohol use > 20 g/day for women or > 30 g/day for men
  • Treatment initiation or dose adjustment of vitamin E, pioglitazone, GLP-1RA, or SGLT-2 inhibitors within 30 days of signing the informed consent or 30 days prior to liver biopsy
  • Treatment initiation or anticipated treatment (>14 consecutive days) with medications known to affect steatosis (e.g., systemic corticosteroids, tamoxifen, valproic acid, methotrexate, tetracycline or amiodarone) within 30 days of signing the informed consent or 30 days prior to liver biopsy
  • Cardiac related:
  • Heart rate less than 60 bpm at screening (visit 1) or at baseline (visit 2)
  • Current diagnosis of severe aortic valve disease
  • History of Accessory arterio-ventricular pathway (e.g., Wolf-Parkinson-White syndrome)
  • History of complete heart block or second degree arterio-ventricular block without pacemaker or implantable cardiac device
  • Current diagnosis of permanent atrial fibrillation
  • Any of the following within the previous 6 months of signing informed consent: myocardial infarction, percutaneous intervention, pacemaker/implantable cardiac device implantation, cardiac surgery, or stroke
  • Current use of the following medications: inotropic drugs such as (dopamine, dobutamine, noradrenaline, milrinone), anti-arrhythmics (amiodarone, dofetilide, sotalol, dronedarone, digoxin), parathyroid hormone analog (teriparatide), sympathomimetics (epinephrine, norepinephrine, dopamine), neuromuscular blocking agents (succinylcholine), calcium supplement, nondihydropyridine calcium channel blockers, ivabradine, and disulfiram.
  • Obesity related:
  • Treatment initiation (in the 30 days prior to signing the informed consent or 30 days prior to liver biopsy) with orlistat, zonisamide, topiramate, phentermine, bupropion, and naltrexone alone or in combination or any other medication that could promote weight loss in the opinion of the investigator
  • Participation (in the 30 days prior to signing the informed consent or 30 days prior to liver biopsy) in an organized diet-based weight reduction program (e.g., WeightWatchers, Optifast)
  • Recent surgical treatment (<6 months of signing informed consent) for obesity
  • General safety related:
  • Presence or history of malignant neoplasms (in the past 5 years prior to screening), except basal and squamous cell skin cancer and any carcinoma in-situ
  • Surgery scheduled or anticipated during the trial period, except for minor surgical procedures, in the opinion of the investigator
  • Language barrier, mental incapacity, unwillingness, or inability to adequately understand or comply with study procedures
  • Known or suspected hypersensitivity to the trial product or related products including allergy to milk, egg, soy, peanuts, and sulfites
  • Recent participation (within 90 days prior to signing the informed consent) in any clinical trial of an approved or non-approved investigational medicinal product
  • Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method
  • Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR < 30 ml/min/1.73 m2
  • TSH > 6 mIU/L or < 0.4 mIU/L at screening
  • Current use of the following medications: calcium supplementation, parathyroid hormone analog (teriparatide), neuromuscular blocking agents (succinylcholine) and disulfiram.
  • Claustrophobia to an extent that would prevent tolerance of MRI
  • Metallic implant that would prevent MRI examination including, metallic foreign body, aneurysm clips, vascular grafts or cardiac implants, neural stimulator, cochlear implant, metallic contraceptive device, body piercing that cannot be removed, cochlear implant, or any other contraindication to MRI

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Tara McPartland contact

tara.mcpartland@yale.edu

United States2 sites, 2 recruiting
  • Yale New Haven Health

    New Haven, Connecticut, 06510

    Bubu Banini, MD, bubu.banini@yale.edu

    Aida Rodriguez Murillo, aida.rodriguezmurillo@yale.edu

    Recruiting
  • Yale New Haven Hospital

    New Haven, Connecticut, 06510

    Bubu Banini, MD, bubu.banini@yale.edu

    Aida Rodriguez Murillo, aida.rodriguezmurillo@yale.edu

    Recruiting

Other trials in United States

About this study

Official title: Clinical Trial of Oral Digoxin In NASH (CODIN)

Nonalcoholic steatohepatitis (NASH) is a severe subtype of nonalcoholic fatty liver disease (NAFLD) which affects 1 in 3 Americans. The mainstay of treatment for NASH, which was recently renamed metabolic associated steatohepatitis (MASH), involves lifestyle interventions to promote weight loss and to treat comorbidities such as hypertension, hyperlipidemia, and diabetes mellitus. There is thus, a substantial unmet need for pharmacological therapies that are effective for treatment of NASH, especially in those with fibrosis which is the main predictor of disease progression and mortality among NASH patients. The repurposing of presently available drugs would help expedite the search for agents effective in treating NASH. The cardiac glycoside digoxin is currently used in the management of heart failure and supraventricular tachyarrhythmias. The investigators and other groups have demonstrated that digoxin protects the liver from various forms of acute and chronic liver injury. The investigators preliminary data in healthy human subject indicate an immunomodulatory effect of low dose oral digoxin with no adverse side effects. This study proposes to demonstrate the clinical benefits of digoxin on NASH and on liver fibrosis, thus supporting the repurposing of digoxin as treatment for NASH.

Read the detailed description

Prospective, randomized, double-blind, placebo-controlled, single center trial of digoxin in patients with nonalcoholic steatohepatitis (NASH).

Primary objective:

To compare the effect of digoxin oral, administered once daily (QD) either as titration-based or weight-based dose, versus placebo on histologic resolution of NASH

Key secondary objectives:

To investigate the effect of digoxin oral, administered once daily (QD) either as titration-based or weight-based dose, compared to placebo on histologic, imaging, and biochemical markers of NASH, and to assess the safety and tolerability of digoxin compared to placebo

Being tested
Digoxin, Placebo
Keywords
NASH, MASH, Metabolic dysfunction associated steatohepatitis, Digoxin, Drug repurposing, Liver fibrosis, Fatty liver disease, NAFLD
Medical subject headings
Non-alcoholic Fatty Liver Disease, Liver Cirrhosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DigoxinDrug

    Taken orally once daily

  • PlaceboDrug

    Matched Placebo taken orally once daily

Study groups in NCT06588699
Study groupRoleWhat they receive
Digoxin (titration-based)ExperimentalDigoxin (titration-based) taken orally once daily. In this arm, the intervention will be administered dosed by weight and renal function using a well-studied digoxin nomogram.
Receives: Drug: Digoxin
Digoxin (weight-based)ExperimentalDigoxin (weight-based) taken orally once daily. In the weight-based digoxin arm, the intervention will be oral digoxin 0.15mcg/kg/day.
Receives: Drug: Digoxin
PlaceboPlacebo comparatorPlacebo, taken orally once daily
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Resolution of nonalcoholic steatohepatitis (NASH) without worsening of fibrosis

    Proportion of participants who achieve resolution of NASH (defined by the NASH Clinical research network [CRN] as a score of 0-1 for inflammation, 0 for hepatocyte ballooning, and any value for steatosis) with no worsening of fibrosis (yes/no).

    Measured: 24 weeks

Secondary outcomes (9)
  1. Improvement in liver fibrosis without worsening of NASH

    Proportion of participants with improvement in liver fibrosis by ≥ 1 stage with no worsening of NASH (yes/no). Worsening of NASH is defined as ≥ 1 increase in lobular inflammation or hepatocyte ballooning according to criteria by the NASH clinical research network (NASH CRN)

    Measured: 24 weeks

  2. Improvement in NAS without worsening of fibrosis

    Proportion of participants with improvement in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 2 with no worsening of fibrosis after 24 weeks (yes/no)

    Measured: 24 weeks

  3. Change in enhanced liver fibrosis (ELF) score

    Change in Enhanced Liver Fibrosis (ELF) score.

    Measured: 24 weeks

  4. Change in alanine aminotransferase (ALT)

    Change in serum alanine aminotransferase (ALT) concentration (pg/ml)

    Measured: 24 weeks

  5. Change in aspartate aminotransferase (AST)

    Change in serum aspartate aminotransferase (AST) concentration (pg/ml)

    Measured: 24 weeks

  6. Change in gamma glutamyl transferase (GGT)

    Change in serum gamma glutamyl transferase (GGT) concentration (pg/ml)

    Measured: 24 weeks

  7. Change in liver stiffness measure (LSM) and controlled attenuation parameter (CAP)

    Change in liver stiffness measure (LSM) and controlled attenuation parameter (CAP) from baseline as measured by transient elastography.

    Measured: 24 weeks

  8. Change in magnetic resonance imaging proton density fat fraction (MRI-PDFF)

    Change in magnetic resonance imaging proton density fat fraction (MRI-PDFF)

    Measured: 24 weeks

  9. Change in Magnetic resonance elastography (MRE)

    Change from baseline in magnetic resonance elastography (MRE)

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2024
  2. Study start5 Jun 2025
  3. Primary completionJan 2029 (estimated)
  4. Study completionJan 2029 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A centrally administered randomization strategy will be used to randomize patients.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
144 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06588699
Sponsor's protocol ID
2000038275
Other IDs
1R01DK134624-01A1
Acronym
CODIN
Status last verified
Mar 2026
First submitted
6 Sep 2024
Last updated
26 May 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.

Publications

  • Jamshed F, Dashti F, Ouyang X, Mehal WZ, Banini BA. New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. World J Gastroenterol. 2023 Mar 28;29(12):1824-1837. doi: 10.3748/wjg.v29.i12.1824.

    PubMed 37032732
  • Dashti F, Jamshed F, Ouyang X, Mehal WZ, Banini BA. Digoxin as an emerging therapy in noncardiac diseases. Trends Pharmacol Sci. 2023 Apr;44(4):199-203. doi: 10.1016/j.tips.2022.10.002. Epub 2022 Nov 14.

    PubMed 36396496
  • Agyapong G, Dashti F, Banini BA. Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies. Ann N Y Acad Sci. 2023 Aug;1526(1):16-29. doi: 10.1111/nyas.15012. Epub 2023 Jul 3.

    PubMed 37400359
  • Ilagan-Ying YC, Banini BA, Do A, Lam R, Lim JK. Screening, Diagnosis, and Staging of Non-Alcoholic Fatty Liver Disease (NAFLD): Application of Society Guidelines to Clinical Practice. Curr Gastroenterol Rep. 2023 Oct;25(10):213-224. doi: 10.1007/s11894-023-00883-8. Epub 2023 Sep 28.

    PubMed 37768417

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Digoxin in people with NASH and NAFLD, run by Yale University at 2 sites 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 38 inclusion and 0 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: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bubu Banini, MD, PhD (203-737-6063 or 203-215-7749, bubu.banini@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Resolution of nonalcoholic steatohepatitis (NASH) without worsening of fibrosis (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06588699, which also lists 4 linked publications.

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 26 May 2026.

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