HyperinsulinemiaPhase 1NCT07403604
Effect of Insulin Lowering on Lipogenesis
A Phase 1 study testing Diazoxide Oral Suspension, 2 mg per kg per dose, Deuterated water (2H2O/D2O), 70% and Insulin Suppression Test (IST) in people with Hyperinsulinemia and Insulin Resistance, run by Columbia University at 1 site in United States.
Trial summary
The goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hyperinsulinemia, Insulin Resistance, Non-Alcoholic Fatty Liver Disease
- What is being tested?
- Diazoxide Oral Suspension, 2 mg per kg per dose, Deuterated water (2H2O/D2O), 70% and Insulin Suppression Test (IST)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2026to 30 Sep 2029
- Phase
- Phase 1
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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.
Who cannot join
- 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
Show all 83Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10032
Joshua R. Cook, MD, PhD, 212-305-6289, jrc2175@cumc.columbia.edu
Joshua R Cook, MD, PhD
About this study
Official title: Human Models of Selective Insulin Resistance: Diazoxide, Part I
The goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). The main question it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects hepatic de novo lipogenesis, a major contributor to MASLD pathophysiology.
Participants will:
Read more
- Take 14 doses of placebo over 7 days, followed 4-12 weeks later by either 14 doses of diazoxide (at 2 mg per kg of body weight per dose [mpk]) or another 14 doses of placebo, over 7 days
- Take 18 doses of heavy (deuterated) water (50 mL each) over 7 days, twice
- Have blood drawn and saliva collected after an overnight fast on four mornings over the course of the study
- Undergo insulin suppression tests (IST) to assess the degree of insulin resistance at the end of each 1-week study period
- Consume their total calculated daily caloric needs as divided into three meals per day
Researchers will compare blood tests at the beginning and end of each 1-week study period in participants randomized (like the flip of a coin) to receive either placebo followed by diazoxide or placebo followed by placebo, to see how the drug treatment affects de novo lipogenesis, serum insulin, plasma glucose, and other serum lipid parameters (triglycerides, free fatty acids), among others.
Read the detailed description
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an under-appreciated complication of lipid dysmetabolism in type 2 diabetes (T2DM). Although it appears that insulin resistance (IR) is a mechanism common to both, the pathophysiology of its connection to unhealthy fat accumulation in the liver remains unclear. The investigators propose that the hyperinsulinemia that accompanies IR drives the excess hepatic de novo lipogenesis (DNL) that characterizes IR-associated MASLD. In other words, hepatic IR may be "selective," such that DNL is more sensitive to stimulation by insulin than is suppression of endogenous glucose production. As such, despite its potential impact on glucose metabolism, lowering insulin levels might attenuate the pro-steatotic drive in patients with IR. The investigators' objective, therefore, is to blunt endogenous insulin secretion using the insulin anti-secretagogue diazoxide in order to assess the impact on DNL.
This is a single-center, randomized, double-blinded, placebo-controlled, crossover clinical trial to determine the lipogenic impact of hyperinsulinemia reduction with diazoxide oral suspension in participants with obesity and insulin resistance (prediabetic state or elevated Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score, + fasting hyperinsulinemia) who are diagnosed with MASLD. Participants will be randomized to one of two groups. Both groups will receive 14 doses of placebo over 7 days. Then, 4-12 weeks later, one group will cross over to receive 14 doses of diazoxide 2 mg per kg of body weight for 7 days, while the other group will receive a second 1-week course of placebo. Participants will consume heavy (deuterated) water for a total of 18 doses of 50 ml over each 1-week study period to measure de novo lipogenesis. They will present for outpatient blood draws and saliva collections after an overnight fast at the start and conclusion of each study period (Study Days 1, 8, 9 and 16), and will undergo formal assessment of insulin resistance by the insulin suppression test (IST) at the end of each study period (Days 8 and 16).
- Conditions
- Hyperinsulinemia, Insulin Resistance, Non-Alcoholic Fatty Liver Disease, Prediabetic State, Obesity
- Being tested
- Placebo, Diazoxide Oral Suspension, 2 mg per kg per dose, Deuterated water (2H2O/D2O), 70%, Insulin Suppression Test (IST)
- Keywords
- Hyperinsulinemia, Insulin Resistance, Metabolic Dysfunction-Associated Steatotic Liver Disease, Non-Alcoholic Fatty Liver Disease, Triglycerides
- Medical subject headings
- Hyperinsulinism, Insulin Resistance, Non-alcoholic Fatty Liver Disease, Prediabetic State, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called Placebo solution
Flavor-approximate placebo consisting of peppermint extract in diet tonic water, thickened with xanthan gum, provided in label-obscured single-use oral syringes at 40 µL per kg per dose. 80% of participants will receive placebo (14 doses over 7 days) during the first 1-week study period, while 20% of participants will receive an additional 14 doses of placebo over 7 days during the second study period, 4-12 weeks later.
Diazoxide Oral Suspension, 2 mg per kg per doseDrug
Also called Proglycem
Eighty percent of participants will ingest diazoxide oral suspension at 2 mg per kg body weight per dose (14 doses over 7 days) during the study's second 1-week treatment period. Blinding will occur by completely covering single-dose oral syringes with labels.
Deuterated water (2H2O/D2O), 70%Drug
Also called Heavy water
All participants will consume 18 aliquots of deuterated water (2H2O/D2O) 50 mL over 7 days during both study periods to assess hepatic de novo lipogenesis. Tracer enrichment will be determined in blood and saliva.
Insulin Suppression Test (IST)Diagnostic test
Participants receive intravenous infusions of regular insulin (32 milliunits [mU] per square meter [m2] per minute [min]), octreotide acetate (25 µg bolus + 0.27 µg/m2/min continuous infusion), and dextrose 20% in water (267 mg/m2/min continuous infusion) for 3 hours. Insulin resistance is reflected as the steady-state plasma glucose (SSPG) during the final 30 minutes of the procedure. IST is performed at the end of both study periods to determine the impact of placebo versus diazoxide on insulin sensitivity.
| Study group | Role | What they receive |
|---|---|---|
| Placebo first, then Diazoxide | Experimental | During the first 1-week study period, participants will ingest a placebo solution at 14 doses over 7 days. During the second 1-week study period, 4-12 weeks later, participants will ingest diazoxide oral suspension at 2 mg per kg body weight per dose (14 doses over 7 days). Blinding will occur by completely covering single-dose oral syringes with labels. 80% of participants will be randomized to this arm. Receives: Drug: Placebo; Drug: Diazoxide Oral Suspension, 2 mg per kg per dose; Drug: Deuterated water (2H2O/D2O), 70%; Diagnostic Test: Insulin Suppression Test (IST) |
| Placebo / Placebo | Placebo comparator | During the first 1-week study period, participants will ingest a placebo solution at 14 doses over 7 days. During the second 1-week study period, 4-12 weeks later, participants will again ingest placebo solution (14 doses over 7 days). Blinding will occur by completely covering single-dose oral syringes with labels. 20% of participants will be randomized to this arm. Receives: Drug: Placebo; Drug: Deuterated water (2H2O/D2O), 70%; Diagnostic Test: Insulin Suppression Test (IST) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic de novo lipogenesis (absolute values)
Percent incorporation of newly synthesized fatty acids into serum or very low-density lipoprotein (VLDL) triglyceride (TG) (units: %)
Measured: Study Days 8 and 16
Hepatic de novo lipogenesis (relative/change)
Percent incorporation of newly synthesized fatty acids into serum or VLDL TG (units: fold difference and/or ∆%)
Measured: Study Days 8 and 16
Secondary outcomes (6)
Fasting plasma/serum insulin (absolute values)
Measurement of fasting endogenous insulin levels during treatment with diazoxide 2 mpk vs. placebo (units: micro-international units [µIU] per mL).
Measured: Study Days 8 and 16
Fasting plasma/serum insulin (relative/change)
Measurement of fasting endogenous insulin levels during treatment with diazoxide 2 mpk vs. placebo (units: fold difference and/or change in µIU/mL).
Measured: Study Days 8 and 16
Fasting plasma glucose
Measurement of fasting plasma glucose levels during treatment with diazoxide 2 mpk vs. placebo (units: mg/dL).
Measured: Study Days 8 and 16
Fasting serum or plasma triglycerides
Measurement of fasting plasma or serum triglyceride levels during treatment with diazoxide 2 mpk vs. placebo (units: mg/dL).
Measured: Study Days 8 and 16
Fasting plasma free fatty acids
Measurement of fasting plasma free fatty acid levels during treatment with diazoxide 2 mpk vs. placebo (units: mmol/L).
Measured: Study Days 8 and 16
Steady state plasma glucose (SSPG) during IST
Measurement of plasma glucose at 10-minute intervals during 30-minute steady-state period at the end of each IST (units: mg/dL)
Measured: At time points of 150, 160, 170, and 180 minutes during each 3-hour IST protocol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start1 Jul 2026
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperinsulinemiaStudies of the same condition, open and under way.
- More trials run by Columbia 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
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will be randomized into one of two study groups. All participants will receive a 1-week placebo treatment, while 4-12 weeks later, one group will receive diazoxide for 1 week while the other will receive a second week of placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Berkeley, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Heidelberg University
- Responsible party
- Principal investigator, Joshua Cook, Columbia University
- Investigators
- Joshua R Cook, MD, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07403604
- Sponsor's protocol ID
- AAAV7588
- Other IDs
- K23DK140614
- Status last verified
- Jul 2026
- First submitted
- 4 Feb 2026
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Models of Selective Insulin Resistance: Diazoxide, Part I
- ClinicalTrials.gov ID
- NCT07403604
- Acronym / sponsor ID
- AAAV7588
- Conditions
- Hyperinsulinemia, Insulin Resistance, Non-Alcoholic Fatty Liver Disease, Prediabetic State, Obesity
- Keywords
- Hyperinsulinemia, Insulin Resistance, Metabolic Dysfunction-Associated Steatotic Liver Disease, Non-Alcoholic Fatty Liver Disease, Triglycerides
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- University of California, Berkeley, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Heidelberg University
- Study start
- 1 Jul 2026 (actual)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 11 Feb 2026 (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 goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). The main question it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects hepatic de novo lipogenesis, a major contributor to MASLD pathophysiology.
Participants will:
- Take 14 doses of placebo over 7 days, followed 4-12 weeks later by either 14 doses of diazoxide (at 2 mg per kg of body weight per dose [mpk]) or another 14 doses of placebo, over 7 days
- Take 18 doses of heavy (deuterated) water (50 mL each) over 7 days, twice
- Have blood drawn and saliva collected after an overnight fast on four mornings over the course of the study
- Undergo insulin suppression tests (IST) to assess the degree of insulin resistance at the end of each 1-week study period
- Consume their total calculated daily caloric needs as divided into three meals per day
Researchers will compare blood tests at the beginning and end of each 1-week study period in participants randomized (like the flip of a coin) to receive either placebo followed by diazoxide or placebo followed by placebo, to see how the drug treatment affects de novo lipogenesis, serum insulin, plasma glucose, and other serum lipid parameters (triglycerides, free fatty acids), among others.
Detailed description
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an under-appreciated complication of lipid dysmetabolism in type 2 diabetes (T2DM). Although it appears that insulin resistance (IR) is a mechanism common to both, the pathophysiology of its connection to unhealthy fat accumulation in the liver remains unclear. The investigators propose that the hyperinsulinemia that accompanies IR drives the excess hepatic de novo lipogenesis (DNL) that characterizes IR-associated MASLD. In other words, hepatic IR may be "selective," such that DNL is more sensitive to stimulation by insulin than is suppression of endogenous glucose production. As such, despite its potential impact on glucose metabolism, lowering insulin levels might attenuate the pro-steatotic drive in patients with IR. The investigators' objective, therefore, is to blunt endogenous insulin secretion using the insulin anti-secretagogue diazoxide in order to assess the impact on DNL.
This is a single-center, randomized, double-blinded, placebo-controlled, crossover clinical trial to determine the lipogenic impact of hyperinsulinemia reduction with diazoxide oral suspension in participants with obesity and insulin resistance (prediabetic state or elevated Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score, + fasting hyperinsulinemia) who are diagnosed with MASLD. Participants will be randomized to one of two groups. Both groups will receive 14 doses of placebo over 7 days. Then, 4-12 weeks later, one group will cross over to receive 14 doses of diazoxide 2 mg per kg of body weight for 7 days, while the other group will receive a second 1-week course of placebo. Participants will consume heavy (deuterated) water for a total of 18 doses of 50 ml over each 1-week study period to measure de novo lipogenesis. They will present for outpatient blood draws and saliva collections after an overnight fast at the start and conclusion of each study period (Study Days 1, 8, 9 and 16), and will undergo formal assessment of insulin resistance by the insulin suppression test (IST) at the end of each study period (Days 8 and 16).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomized into one of two study groups. All participants will receive a 1-week placebo treatment, while 4-12 weeks later, one group will receive diazoxide for 1 week while the other will receive a second week of placebo.
| Arm | Type | Receives |
|---|---|---|
| Placebo first, then Diazoxide | Experimental | Drug: Placebo, Drug: Diazoxide Oral Suspension, 2 mg per kg per dose, Drug: Deuterated water (2H2O/D2O), 70%, Diagnostic Test: Insulin Suppression Test (IST)During the first 1-week study period, participants will ingest a placebo solution at 14 doses over 7 days. During the second 1-week study period, 4-12 weeks later, participants will ingest diazoxide oral suspension at 2 mg per kg body weight per dose (14 doses over 7 days). Blinding will occur by completely covering single-dose oral syringes with labels. 80% of participants will be randomized to this arm. |
| Placebo / Placebo | Placebo comparator | Drug: Placebo, Drug: Deuterated water (2H2O/D2O), 70%, Diagnostic Test: Insulin Suppression Test (IST)During the first 1-week study period, participants will ingest a placebo solution at 14 doses over 7 days. During the second 1-week study period, 4-12 weeks later, participants will again ingest placebo solution (14 doses over 7 days). Blinding will occur by completely covering single-dose oral syringes with labels. 20% of participants will be randomized to this arm. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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)
Key exclusion criteria (83 listed)
- Unable to provide informed consent in English or Spanish
- Concerns arising at screening visit (any of the following):
- Reproductive concerns
- Concerns related to glucose metabolism
- Concerns related to lipid metabolism
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 |
|---|---|---|
| PlaceboAlso: Placebo solutionFlavor-approximate placebo consisting of peppermint extract in diet tonic water, thickened with xanthan gum, provided in label-obscured single-use oral syringes at 40 µL per kg per dose. 80% of participants will receive placebo (14 doses over 7 days) during the first 1-week study period, while 20% of participants will receive an additional 14 doses of placebo over 7 days during the second study period, 4-12 weeks later. | Drug | Placebo / Placebo, Placebo first, then Diazoxide |
| Diazoxide Oral Suspension, 2 mg per kg per doseAlso: ProglycemEighty percent of participants will ingest diazoxide oral suspension at 2 mg per kg body weight per dose (14 doses over 7 days) during the study's second 1-week treatment period. Blinding will occur by completely covering single-dose oral syringes with labels. | Drug | Placebo first, then Diazoxide |
| Deuterated water (2H2O/D2O), 70%Also: Heavy waterAll participants will consume 18 aliquots of deuterated water (2H2O/D2O) 50 mL over 7 days during both study periods to assess hepatic de novo lipogenesis. Tracer enrichment will be determined in blood and saliva. | Drug | Placebo / Placebo, Placebo first, then Diazoxide |
| Insulin Suppression Test (IST)Participants receive intravenous infusions of regular insulin (32 milliunits [mU] per square meter [m2] per minute [min]), octreotide acetate (25 µg bolus + 0.27 µg/m2/min continuous infusion), and dextrose 20% in water (267 mg/m2/min continuous infusion) for 3 hours. Insulin resistance is reflected as the steady-state plasma glucose (SSPG) during the final 30 minutes of the procedure. IST is performed at the end of both study periods to determine the impact of placebo versus diazoxide on insulin sensitivity. | Diagnostic test | Placebo / Placebo, Placebo first, then Diazoxide |
Primary outcome
Hepatic de novo lipogenesis (absolute values)
Time frame: 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)
Time frame: Study Days 8 and 16
Percent incorporation of newly synthesized fatty acids into serum or VLDL TG (units: fold difference and/or ∆%)
6 secondary outcomes
Fasting plasma/serum insulin (absolute values)
Time frame: Study Days 8 and 16
Fasting plasma/serum insulin (relative/change)
Time frame: Study Days 8 and 16
Fasting plasma glucose
Time frame: Study Days 8 and 16
Fasting serum or plasma triglycerides
Time frame: Study Days 8 and 16
Fasting plasma free fatty acids
Time frame: Study Days 8 and 16
Steady state plasma glucose (SSPG) during IST
Time frame: At time points of 150, 160, 170, and 180 minutes during each 3-hour IST protocol
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- Individual participant dataSharing planned: Yes
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Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Not yet recruitingPhase 2
Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity
Insulin Resistance, Obesity
Recruiting
Effects of Urolithin A Supplementation on Glucose Metabolism in Healthy Adults 55 >= Years Old: A Randomized Triple-Masked Controlled Clinical Trial
Healthy Volunteer
Not yet recruitingPhase 2
Effects of Meal Macronutrients on Postprandial Lipids
Nephrotic Syndrome, Lipodystrophy
RecruitingObservational study
Food-i-Sense Analytics: Integrating AI Into Continuous Glucose Monitoring Data Analysis for Precision Nutrition.
Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Artificial Intelligence Mobile Application
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.
Joshua R Cook, MD, PhD principal investigator
Columbia 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 Diazoxide Oral Suspension, 2 mg per kg per dose, Deuterated water (2H2O/D2O), 70% and Insulin Suppression Test (IST) in people with Hyperinsulinemia and Insulin Resistance, run by Columbia 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 14 inclusion and 83 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 6 Jul 2026. 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?
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 Ishwari Nagnur, BA (2123059336, imn2113@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic de novo lipogenesis (absolute values) (time frame: Study Days 8 and 16). 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?
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 6 Jul 2026.