Actively Recruiting
Effect of Insulin Lowering on Lipogenesis
Led by Columbia University · Updated on 2026-04-09
25
Participants Needed
1
Research Sites
174 weeks
Total Duration
On this page
Sponsors
C
Columbia University
Lead Sponsor
U
University of California, Berkeley
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Effect of Insulin Lowering on Lipogenesis
Who Can Participate
Eligibility Criteria
You may qualify if you...
- 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) with steatosis score S1-S3 and fibrosis score F0-F2
- Evidence of insulin resistance, including prediabetes (Hemoglobin A1c 5.7-6.4%) or impaired fasting glucose (100-125 mg/dL after at least 8-hour fast), or Homeostasis Model of Insulin Resistance (HOMA-IR) score ≥ 2.73
- Fasting hyperinsulinemia (fasting insulin level ≥ 13 µU/mL) on screening labs
- Written informed consent obtained in English or Spanish
You will not qualify if you...
- Unable to provide informed consent in English or Spanish
- Documented weight loss of ≥ 5.0% of baseline within the previous 3 months
- Abnormal blood pressure: systolic < 90 mm Hg or > 160 mm Hg, diastolic < 60 mm Hg or > 100 mm Hg
- Resting heart rate < 55 bpm or ≥ 110 bpm
- Abnormal screening electrocardiogram
- Laboratory evidence of diabetes mellitus (Hemoglobin A1c ≥ 6.5% or fasting plasma glucose ≥ 126 mg/dL)
- Positive pregnancy test in women of childbearing potential
- Liver function abnormalities: transaminases > 3.0 times the upper limit of normal or total bilirubin > 1.25 times upper limit
- Fasting triglycerides > 500 mg/dL
- Clinically significant abnormal serum electrolytes or creatinine with estimated glomerular filtration rate < 60 mL/min/1.73 m2
- Abnormal blood counts: hemoglobin < 10 g/dL, low white blood cell or platelet counts
- Uric acid level above upper limit of normal
- Women currently pregnant or breastfeeding
- History of diabetes mellitus or gestational diabetes within 5 years
- Use of antidiabetic medications except metformin within 90 days prior to screening
- Known familial lipid disorders or recent use of certain lipid-lowering medications
- History of pancreatic disease, cardiovascular disease beyond uncomplicated hypertension, chronic kidney disease stage 3 or higher, chronic liver diseases other than uncomplicated MASLD
- Gout, chronic infections (HBV, HCV, HIV), malabsorptive conditions, active seizure disorders, recent psychiatric diseases with certain treatments
- Known glucose-6-phosphate dehydrogenase deficiency or other significant endocrinopathies
- Venous thromboembolic disease or required anticoagulation
- Active malignancy except certain skin or early thyroid cancers
- Risk factors for volume overload or hypotension
- Use of certain medications within 90 days prior to screening
- History of specific bariatric surgeries within the past year
- Alcohol overuse or regular tobacco/nicotine use
- Positive urine drug screen except for prescribed medications or marijuana with agreement to abstain from alcohol
- Atypical circadian rhythm due to night shift work within 30 days
- Recent severe infection or febrile illness
- Any condition or lab value posing unacceptable risk or interfering with study data
- Known allergies or hypersensitivity to study products or related materials
- Concurrent enrollment in other clinical drug studies or recent use of biological agents
AI-Screening
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Trial Site Locations
Total: 1 location
1
Columbia University Irving Medical Center
New York, New York, United States, 10032
Actively Recruiting
Research Team
I
Ishwari Nagnur, BA
CONTACT
J
Joshua Cook
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
BASIC_SCIENCE
Number of Arms
2
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