Nonalcoholic SteatohepatitisPhase 2NCT04216693
Digoxin for Patients With Non-alcoholic Steatohepatitis (NASH)
A Phase 2 study testing Digoxin tablet in people with Nonalcoholic Steatohepatitis, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
Trial summary
The purpose of this study is to assess if digoxin is safe and efficacious in treating patients with non-alcoholic steatohepatitis (NASH) within the approved target range of 0.7 to 1 ng/ml. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis
- What is being tested?
- Digoxin tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2020to 1 Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization.
- Males or females between 18-70 years old with a clinically confirmed diagnosis of NASH within the last 12 months of Screening Visit.
- BMI between 25 and 45 kg/m2.
- Negative urine drugs-of-abuse screen.
- Negative alcohol screen.
- Negative urine pregnancy test and agree to use a medically acceptable method of contraception throughout the study and for 1 month after completing the study. Medically acceptable methods of contraception that may be used by the subject and/or partner include, but are not limited to: abstinence, oral contraception, NuvaRing® or transdermal systems, diaphragm with vaginal spermicide, intra uterine device, condom and partner using vaginal spermicide, at least 6 months after surgical sterilization, progestin implant or injection, or postmenopausal female (no menstrual period for > 2 years) or vasectomy (>6 months).
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- Normal EKG.
- Deemed normal age-adjusted creatinine level.
- NAS score greater than 5.
- Steatosis greater than 8% on liver biopsy. Able and willing to comply with the protocol and available for all scheduled clinic visits and telephone calls.
Who cannot join
- Known cardiovascular disease
- Subjects who have previously received digoxin or who have history of hypersensitivity, allergy, intolerance or contraindication to digoxin.
- Requiring any of the following medications during the duration of the study:
- Potassium-depleting diuretics
- Calcium, particularly if administered rapidly by the intravenous route
- Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, erythromycin, clarithromycin (and possibly other macrolide antibiotics), tetracycline, propantheline, diphenoxylate, antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, metoclopramide, rifampin, quinine, penicillamine, thyroid hormone, sympathomimetics. Succinylcholine, calcium channel blockers, beta-blockers, carvedilol, and any drug that may cause a significant deterioration in renal function.
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- History of cirrhosis based on imaging or clinical criteria and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.
- Platelet count < 100,000/ul
- Albumin below 3.5 g/dl
- Serum ferritin > 800 ng/mL
- Anti-neutrophil antibody above 1: 160
- International normalized ratio (INR) > 1.2History of liver transplantation
- History of hepatocellular carcinoma (HCC)
- History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous carcinoma at the time of Screening visit
- Active, serious infections that requires parenteral antibiotic or antifungal therapy within 30 days prior to Screening visit.
- Any ≥Grade 3 laboratory abnormality as defined by Toxicity Grading Scale, with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:
- Subjects with pre-existing diabetes or with asymptomatic glucose ≥Grade 3 elevations;
- Subjects with asymptomatic triglyceride or cholesterol ≥Grade 3 elevations;
- Subjects with asymptomatic ALT and/or AST > 4 time above normal
- Females who are pregnant or breastfeeding.
- Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents and immunomodulating agents (such as systemic corticosteroids, interleukins, interferons).
- Use of any experimental medications within the last 6 months of Screening Visit.
- Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements.
- Familial dyslipidemia.
- Weight loss of >5% within 6 months prior to Screening, based on subject's reporting
- Currently or participated in a weight loss program within the last 6 months.
- Any history of bariatric surgery.
- Diabetes mellitus Type I
- Daily alcohol intake >20 ml (2 units)/day for women and 30 ml (3 units)/day for men (on average), as per Alcohol Use Disorders Identification Test (AUDIT) questionnaire at Screening and plan to consume the same alcohol amount referenced above during the trial.
- Hemoglobin A1c >9.0%
- Treatment initiation or dose change within 3 months of Screening with Vitamin E, or any of the following anti- diabetic medications: DPP-4 inhibitor, GLP-1 receptor agonists (such as Januvia [sitagliptin], Byetta [incretin], etc.), pioglitazone, or SGLT2 inhibitors ("gliflozin" drugs), Metformin, fibrates, statins, insulin, Vitamin D, or sulfonylurea.
- Use of any immunosuppressive medication, anti-inflammatory monoclonal antibody treatment, or chronic systemic corticosteroids >10 mg prednisone-equivalent concurrently or within 1 year prior to Screening.
- Uncontrolled or clinically unstable thyroid disease, in the judgment of the Principal Investigator.
- History or presence of hepatitis B or C or human immunodeficiency virus (HIV).
- Uncontrolled arterial hypertension
- Any severe, acute, or chronic medical or psychiatric condition that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the subject inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
China1 site
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008
About this study
Official title: Efficacy and Safety of Digoxin in the Treatment of Adults Patients With Non-alcoholic Steatohepatitis: a Multi-center, Randomized, Placebo-controlled Trial
The purpose of this study is to assess if digoxin is safe and efficacious in treating patients with non-alcoholic steatohepatitis (NASH) within the approved target range of 0.7 to 1 ng/ml.
Read the detailed description
This study is a phase II, open labeled, multi-center, prospective, randomized, placebo controlled clinical trial to evaluate the efficacy and safety of digoxin in the treatment of nonalcoholic steatohepatitis. The participants will take study drug digoxin, which is approved by FDA for the treatment of congestive heart failure (CHF), orally daily based on the body weight, titrated to the level of 0.7 to 1 ng/ml for total of 6 cycles (4 weeks/cycle). A liver biopsy will be performed at the beginning of the study and 24 weeks after randomization to evaluate the efficacy of digoxin in the treatment of nonalcoholic steatohepatitis.
- Conditions
- Nonalcoholic Steatohepatitis
- Being tested
- Digoxin tablet, Placebo
- Keywords
- Nonalcoholic Steatohepatitis, Digoxin, Non-Alcoholic Fatty Liver Disease
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Digoxin tabletDrug
The NASH patients in experimental group will take digoxin tablets orally with the goal of achieving a serum digoxin concentration of 0.7-1 ng/ml for 24 weeks.
PlaceboOther
The control group will receive the digoxin-like placebo treatment.
| Study group | Role | What they receive |
|---|---|---|
| Digoxin tablet | Experimental | Patients will be given digoxin orally daily for 24 weeks. The initial dose will be selected with the goal of achieving a serum digoxin concentration of 0.7-1 ng/ml, a dose range recommended for heart failure patients. A dose of 0.0625, 0.125 or 0.25 mg daily will be selected based on a normogram. Receives: Drug: Digoxin tablet |
| Placebo | Placebo comparator | Digoxin-like oral placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Two point change in histological NAFLD activity score (NAS)
Non-alcoholic fatty liver disease score (NAS) is a histological classification to assess the severity of liver steatosis, lobular inflammation and ballooning in the liver biopsy, which ranges from 0-8 with the increase in number representing a worse outcome. Therefore, the efficacy improvement was to be at least 2 points in lowering the score.
Measured: Baseline, 24 weeks
Proportion of subjects with at least a 30% change in % steatosis relative to screening
Liver steatosis is graded based on the percentage of fat within the hepatocytes: grade 0 (healthy, <5%), grade 1 (mild, 5%-33%), grade 2 (moderate, 34%-66%), and grade 3 (severe, >66%). the efficacy improvement was to be proportion of subjects with at least a 30% decrease in % steatosis relative to screening.
Measured: Baseline, 24 weeks
Secondary outcomes (3)
Change in the mean concentration of serum aspartate aminotransferase (AST)
Measured: 0, 2, 4, 6, 11, 24 weeks
Change in the mean concentration of serum alanine aminotransferase (ALT)
Measured: 0, 2, 4, 6, 11, 24 weeks
Change in liver histological fibrosis staging
Fibrosis staging was measured as following criteria: 0=none, 1=perisinusoidal or periportal fibrosis, 2=perisinusoidal and portal/periportal fibrosis, 3=bridging fibrosis, and 4=cirrhosis.the definition of fibrosis stages improvement requires at least one stage.
Measured: Baseline, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2020
- Study start1 Jun 2020 (estimated)
- Primary completion1 Dec 2022 (estimated)
- Study completion1 Jun 2023 (estimated)
Why it stopped: Administrative decision to terminate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Yale University
- Responsible party
- Principal investigator, Beicheng Sun, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04216693
- Sponsor's protocol ID
- v1.0 20200101
- Status last verified
- Jul 2022
- First submitted
- 31 Dec 2019
- Last updated
- 22 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Starkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1alpha Transactivation in Steatohepatitis. Cell Metab. 2018 Feb 6;27(2):339-350.e3. doi: 10.1016/j.cmet.2018.01.007.
PubMed 29414684
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Digoxin in the Treatment of Adults Patients With Non-alcoholic Steatohepatitis: a Multi-center, Randomized, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT04216693
- Acronym / sponsor ID
- v1.0 20200101
- Conditions
- Nonalcoholic Steatohepatitis
- Keywords
- Nonalcoholic Steatohepatitis, Digoxin, Non-Alcoholic Fatty Liver Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Administrative decision to terminate.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolUniversity, hospital or other
- Collaborators
- Yale University
- Study start
- 1 Jun 2020 (estimated)
- Primary completion
- 1 Dec 2022 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 3 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess if digoxin is safe and efficacious in treating patients with non-alcoholic steatohepatitis (NASH) within the approved target range of 0.7 to 1 ng/ml.
Detailed description
This study is a phase II, open labeled, multi-center, prospective, randomized, placebo controlled clinical trial to evaluate the efficacy and safety of digoxin in the treatment of nonalcoholic steatohepatitis. The participants will take study drug digoxin, which is approved by FDA for the treatment of congestive heart failure (CHF), orally daily based on the body weight, titrated to the level of 0.7 to 1 ng/ml for total of 6 cycles (4 weeks/cycle). A liver biopsy will be performed at the beginning of the study and 24 weeks after randomization to evaluate the efficacy of digoxin in the treatment of nonalcoholic steatohepatitis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Digoxin tablet | Experimental | Drug: Digoxin tabletPatients will be given digoxin orally daily for 24 weeks. The initial dose will be selected with the goal of achieving a serum digoxin concentration of 0.7-1 ng/ml, a dose range recommended for heart failure patients. A dose of 0.0625, 0.125 or 0.25 mg daily will be selected based on a normogram. |
| Placebo | Placebo comparator | Other: PlaceboDigoxin-like oral placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization.
- Males or females between 18-70 years old with a clinically confirmed diagnosis of NASH within the last 12 months of Screening Visit.
- BMI between 25 and 45 kg/m2.
- Negative urine drugs-of-abuse screen.
- Negative alcohol screen.
Key exclusion criteria (36 listed)
- Known cardiovascular disease
- Subjects who have previously received digoxin or who have history of hypersensitivity, allergy, intolerance or contraindication to digoxin.
- Requiring any of the following medications during the duration of the study:
- History of cirrhosis based on imaging or clinical criteria and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.
- Platelet count < 100,000/ul
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 |
|---|---|---|
| Digoxin tabletThe NASH patients in experimental group will take digoxin tablets orally with the goal of achieving a serum digoxin concentration of 0.7-1 ng/ml for 24 weeks. | Drug | Digoxin tablet |
| PlaceboThe control group will receive the digoxin-like placebo treatment. | Other | Placebo |
Primary outcome
Two point change in histological NAFLD activity score (NAS)
Time frame: Baseline, 24 weeks
Non-alcoholic fatty liver disease score (NAS) is a histological classification to assess the severity of liver steatosis, lobular inflammation and ballooning in the liver biopsy, which ranges from 0-8 with the increase in number representing a worse outcome. Therefore, the efficacy improvement was to be at least 2 points in lowering the score.
Proportion of subjects with at least a 30% change in % steatosis relative to screening
Time frame: Baseline, 24 weeks
Liver steatosis is graded based on the percentage of fat within the hepatocytes: grade 0 (healthy, <5%), grade 1 (mild, 5%-33%), grade 2 (moderate, 34%-66%), and grade 3 (severe, >66%). the efficacy improvement was to be proportion of subjects with at least a 30% decrease in % steatosis relative to screening.
3 secondary outcomes
Change in the mean concentration of serum aspartate aminotransferase (AST)
Time frame: 0, 2, 4, 6, 11, 24 weeks
Change in the mean concentration of serum alanine aminotransferase (ALT)
Time frame: 0, 2, 4, 6, 11, 24 weeks
Change in liver histological fibrosis staging
Time frame: Baseline, 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
- Results publication: PubMed 29414684Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Starkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1alpha Transactivation in Steatohepatitis. Cell Metab. 2018 Feb 6;27(2):339-350.e3. doi: 10.1016/j.cmet.2018.01.007.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Digoxin tablet in people with Nonalcoholic Steatohepatitis, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
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 10 inclusion and 36 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: withdrawn, as of the sponsor's last update on 22 Feb 2023. 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 China. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Two point change in histological NAFLD activity score (NAS) (time frame: Baseline, 24 weeks). The study lists 2 primary outcomes in all. 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 NCT04216693, which also lists 1 linked publication.
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 22 Feb 2023.