Study on Insulin Lowering for Fatty Liver Disease
This study is looking at how lowering insulin levels might affect fat buildup in the liver for people with obesity and insulin resistance (when your body doesn't respond well to insulin). Researchers want to see if a drug called diazoxide can reduce the liver's fat production (hepatic de novo lipogenesis). You might be able to join if you are 18-65 years old, have a BMI between 30-45 kg/m2, and have metabolic dysfunction-associated steatotic liver disease (MASLD), also known as fatty liver disease. The study will compare diazoxide to a placebo (an inactive substance) over two separate one-week periods. The main goal is to measure changes in liver fat production.
- Study design
- This is a randomized, double-blinded, placebo-controlled crossover study involving 25 participants. This means you would receive both the study drug and a placebo at different times, without knowing which you are getting.
- What's involved
- You would take 14 doses of either placebo or diazoxide over 7 days, twice. You would also take 18 doses of deuterated water (heavy water) over 7 days, twice, and have blood and saliva collected after an overnight fast on four mornings.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your liver fat production will be measured at Study Days 8 and 16.
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NCT07403604
Effect of Insulin Lowering on Lipogenesis
Recruiting
PHASE1Ages 18–65InterventionalBasic scienceColumbia UniversityInvestigator-initiated
~25 participants
Updated 2026-07-06 on ClinicalTrials.gov
What's tested:PlaceboDiazoxide Oral Suspension, 2 mg per kg per doseDeuterated water (2H2O/D2O), 70%Insulin Suppression Test (IST)
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Hepatic de novo lipogenesis (absolute values)
Measured over Study Days 8 and 16
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesNew York1
Study leadership
- Joshua R Cook, MD, PhD · PRINCIPAL_INVESTIGATOR · Columbia University
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Adults aged 18-65 years
Body mass index of 30-45 kg/m2
Able to understand written and spoken English and/or Spanish
Able to have pre-randomization screening labs drawn and study protocol initiated within 60 days of eligibility determination
Presence of uncomplicated metabolic dysfunction-associated steatotic liver disease (MASLD) by vibration-controlled transient elastography (VCTE)
Steatosis score of S1-S3
Fibrosis score of F0-F2 (Note that if VCTE result is available from within past 6 months, then do not have to repeat VCTE for study purposes)
Evidence of insulin resistance, represented by any or all of the following criteria:
Meeting either of the American Diabetes Association's definitions for prediabetes or impaired fasting glucose (IFG) on screening labs:
Prediabetes: Hemoglobin A1c 5.7-6.4%
IFG: plasma glucose of 100-125 mg dL-1 after ≥ 8-h fast
Homeostasis Model of Insulin Resistance (HOMA-IR) score ≥ 2.73
Fasting hyperinsulinemia (fasting insulin level ≥ 13 μU/mL) on screening labs
Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
Exclusion
Unable to provide informed consent in English or Spanish
Concerns arising at screening visit (any of the following):
Documented weight loss of ≥ 5.0% of baseline within the previous 3 months
Abnormal blood pressure (including on treatment, if prescribed)
Systolic blood pressure (SBP) \< 90 mm Hg or \> 160 mm Hg, and/or
Diastolic blood pressure (DBP) \< 60 mm Hg or \> 100 mm Hg
Resting heart rate \< 55 bpm or ≥ 110 bpm
Abnormal screening electrocardiogram (or if on file, performed within previous 90 days)
Laboratory evidence of diabetes mellitus:
Hemoglobin A1c ≥ 6.5%, and/or
Fasting plasma glucose ≥ 126 mg/dL
Positive qualitative serum β-human chorionic gonadotropin (β-hCG, i.e., pregnancy test) in women of childbearing potential
Liver function abnormalities: transaminases (aspartate aminotransferase or alanine aminotransferase) \> 3.0 x the upper limit of normal, and/or total bilirubin \> 1.25 x the upper limit of normal
Abnormal screening fasting triglycerides \> 500 mg/dL
Abnormal screening serum electrolytes that are considered clinically significant according to the clinical judgment of the PI
Creatinine equating to estimated glomerular filtration rate \< 60 mL/min/1.73 m2
Abnormal screening blood counts (any of the following):
Hemoglobin \< 10 g/dL
White blood cell count below the lower limit of normal for sex
Platelet count below the lower limit of normal for sex
Uric acid level above the upper limit of normal
Reproductive concerns
Women currently pregnant (tested by serum and/or urine β-hCG)
Women currently breastfeeding
Concerns related to glucose metabolism
History of having met any of the American Diabetes Association's definitions of diabetes mellitus (i.e., overt diabetes):
Hemoglobin A1c ≥ 6.5%
Plasma glucose ≥ 126 mg/dL after 8-h fast
Plasma glucose of ≥ 200 mg/dL at 2 h after ingestion of a 75-g glucose load
Random plasma glucose ≥ 200 mg/dL associated with typical hyperglycemic symptoms, diabetic ketoacidosis, or hyperglycemic-hyperosmolar state
History of gestational diabetes mellitus within the previous 5 years
Use of antidiabetic medications except metformin within the 90 days prior to screening
Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)
Concerns related to lipid metabolism
Known diagnoses of familial hypercholesterolemia, familial combined hyperlipidemia, or familial hyperchylomicronemia
Use of fibrates, prescription-strength omega-3 fatty acids, or high-dose niacin within the 90 days prior to screening:
Known, documented history (i.e., not to be newly screened/tested for study purposes), at the time of screening, of any of the following medical conditions:
Pancreatic pathology, including but not limited to neoplasia, pancreatitis, pancreatectomy
Cardiovascular disease (N.B. uncomplicated hypertension is not exclusionary)
Atherosclerotic cardiovascular disease: stable or unstable angina, myocardial infarction, ischaemic or hemorrhagic stroke, or transient ischaemic attack, peripheral arterial disease (claudication), use of dual antiplatelet therapy (aspirin + P2Y12 inhibitor), history of percutaneous coronary intervention
Heart rhythm abnormalities
Congestive heart failure of any New York Heart Association class
Symptomatic valvular heart disease (e.g., aortic stenosis)
Pulmonary hypertension
Chronic kidney disease, Stage 3 or higher (estimated glomerular filtration rate \< 60 mL/min/ 1.73 m2), of any cause
Chronic liver disease other than uncomplicated MASLD, including but not limited to:
Advanced liver fibrosis, as determined by non-invasive testing, including fibrosis scores of F3-F4 on VCTE
Cirrhosis of any etiology
Autoimmune hepatitis or other rheumatologic disorder affecting the liver
Biliopathy (e.g., progressive sclerosing cholangitis, primary biliary cholangitis)
Chronic liver infection (e.g., viral hepatitis, parasitic infestation)
Hepatocellular carcinoma
Infiltrative disorders (e.g., sarcoidosis, hemochromatosis, Wilson disease)
Gout
Chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
Malabsorptive conditions
Active seizure disorder (including controlled with antiepileptic drugs)
Psychiatric diseases that are or have been decompensated within 1 year of screening, and/or require use of antipsychotic drugs associated with significant weight gain/metabolic dysfunction (e.g., clozapine, olanzapine), monoamine oxidase inhibitors, tricyclic antidepressants, or lithium
Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
Other clinically significant endocrinopathies
Venous thromboembolic disease (deep vein thrombosis or pulmonary embolism) or any required use of therapeutic anticoagulation
Active malignancy, or hormonally active benign neoplasm, except allowances for non-melanoma skin cancer and differentiated thyroid cancer (Stage I only)
Clinical concern for increased risk of volume overload or hypotension (SBP \<90 and/or DBP \<60 mm Hg), including due to medications and/or heart/liver/kidney problems, as listed above
Clinical concern for increased risk of volume overload or hypotension (SBP \<90 and/or DBP \<60 mm Hg), including due to medications and/or heart/liver/kidney problems, as listed above
Use of certain medications currently or within 90 d prior to screening:
Prescribed medications used for any of the indications in the preceding list of excluded conditions, or their use within 90 d prior to screening, except allowances for:
Statins for primary prevention of cardiovascular disease
Use of drugs prescribed for indications other than the exclusionary diagnoses/purposes listed above (e.g., non-hydantoin antiepileptic drugs used for non-seizure indications, angiotensin converting enzyme inhibitor/angiotensin receptor blocker used for uncomplicated hypertension rather than for congestive heart failure, etc.)
Vasodilating drugs for any indication: hydralazine, nitrates, phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil), minoxidil (oral)
Phenytoin or fosphenytoin for any indication
Oral or parenteral corticosteroids (at greater than prednisone 5 mg daily, or equivalent) for more than 3 days within the previous 90 days; topical and inhaled formulations are permitted
History of certain weight-loss (bariatric) surgeries, including:
Roux-en-Y gastric bypass
Biliopancreatic diversion
Restrictive procedures (lap band, sleeve gastrectomy) performed within past year
Clinical concern for alcohol overuse, including based on chart review and/or by participant's report of consuming more than 14 standard drinks per week for males or more than 7 standard drinks per week for females
Regular use of tobacco, either daily or an average of at least 1 cigarette per day, and/or nicotine vaping more than 1 day per week
Positive urine drug screen, except for lawfully prescribed medications or marijuana/tetrahydrocannabinol positivity, provided that the participant agrees not to use it during the same period that they will abstain from alcohol)
Atypical circadian rhythm, such as due to night shift work, within 30 days of screening or expected within 30 days of each treatment period
History of severe infection or ongoing febrile illness within 14 days of screening
Any other disease or condition or laboratory value that, in the opinion of the investigator, would place the participant at an unacceptable risk and/or interfere with the analysis of study data.
Known allergy/hypersensitivity to any component of the medicinal product formulations (including sulfa drugs), other biologics, intravenous (IV) infusion equipment, plastics, adhesive or silicone, history of infusion site reactions with IV administration of other medicines, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
Concurrent enrollment in another clinical study of any investigational drug therapy or use of any biologicals within 5 half-lives of an investigational agent or biologic
What this trial measures
- Hepatic de novo lipogenesis (absolute values)Study Days 8 and 16
Percent incorporation of newly synthesized fatty acids into serum or very low-density lipoprotein (VLDL) triglyceride (TG) (units: %)
- Hepatic de novo lipogenesis (relative/change)Study Days 8 and 16
Percent incorporation of newly synthesized fatty acids into serum or VLDL TG (units: fold difference and/or ∆%)