Digoxin In NASH (CODIN)

Launched by YALE UNIVERSITY · Sep 6, 2024

Keywords

ClinConnect Summary

The clinical trial titled "Digoxin In NASH (CODIN)" is studying the use of digoxin, a medication typically used for heart problems, to see if it can help patients with nonalcoholic steatohepatitis (NASH), a serious liver condition. NASH is a more severe form of nonalcoholic fatty liver disease that affects many people, and currently, there are limited treatment options. The researchers hope that digoxin can reduce liver inflammation and improve liver health in patients who have confirmed NASH and some degree of liver scarring (fibrosis).

To participate in this trial, individuals must be between the ages of 65 and 74 and have been diagnosed with NASH through a liver biopsy in the last six months. They also need to have stable body weight and specific scores on their liver biopsy indicating the severity of their condition. Participants will undergo additional liver biopsies at the start of the study and again after 24 weeks to assess their progress. It’s important to note that certain health conditions and recent treatments may exclude individuals from joining the trial. This study is still in the planning stages and hasn't started recruiting participants yet.

Gender

ALL

Eligibility criteria

• • Inclusion Criteria
• • 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
• • 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