Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-04-06 @ 5:24 AM
Study NCT ID:
NCT07403604
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-11
First Post:
2026-02-04
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Insulin Lowering on Lipogenesis
Sponsor:
Columbia University
Organization:
Study Overview
Official Title:
Human Models of Selective Insulin Resistance: Diazoxide, Part I
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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). 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.
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, and will undergo formal assessment of insulin resistance by the insulin suppression test (IST) at the end of each study period.
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, and will undergo formal assessment of insulin resistance by the insulin suppression test (IST) at the end of each study period.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| K23DK140614 | NIH | None | https://reporter.nih.gov/quic… | View |