Ignite Creation Date:
2024-05-06 @ 8:22 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06354088
Status:
RECRUITING
Last Update Posted:
2024-04-29
First Post:
2024-04-03
Brief Title:
Human Models of Selective Insulin Resistance Alpelisib Part I
Sponsor:
Columbia University
Organization:
Columbia University
Study Overview
Official Title:
Human Models of Selective Insulin Resistance Alpelisib Part I
Status:
RECRUITING
Status Verified Date:
2024-04
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 understand how the blood sugar-lowering hormone insulin works in healthy adults versus those who are at risk for type 2 diabetes The study will use a drug called alpelisib which interferes with insulins actions in the body to answer the studys main question does the liver continue to respond to insulins stimulation of fat production even when it loses the ability to stop making glucose sugar in response to insulin Researchers will compare the impact of single doses of both alpelisib and placebo inert non-drug in random order like flipping a coin in study participants Participants will be asked to stay twice overnight in the hospital take single doses of alpelisib and placebo one or the other on each of the two hospital stays and receive intravenous into the vein infusions of non-radioactive tracer molecules that allow researchers to measure the production of glucose sugar and fats by the liver Measurements will be done both overnight while participants are asleep and fasting not eating or drinking other than water and while consuming a standardized diet of nutritional beverages during the following day
The objective is to evaluate the effect of lowering insulin levels while maintaining constant mild hyperglycemia on plasma glucose and lipid levels
The objective is to evaluate the effect of lowering insulin levels while maintaining constant mild hyperglycemia on plasma glucose and lipid levels
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 mechanisms linking IR to unhealthy fat accumulation in liver remains unclear Pure IR would be expected to disinhibit hepatic glucose production while dampening hepatic triglyceride TG biosynthesis but the excessive hepatic de novo lipogenesis DNL of IR-associated MASLD suggests that hepatic IR is selective However the concept of IR selectivity is controversial and because of clinical heterogeneity lead-time discrepancies co-morbidities and medication effects parsing out this pathophysiologic conundrum in humans is challenging The investigators plan to test whether the multifactorial IR in patients at risk of T2DMMASLD is selective by determining if inducing a discrete pure form of IR via pharmacologic inhibition of phosphoinositide-3-kinase PI3K with alpelisib versus placebo attenuates excessive DNL Investigators will also study this question in healthy insulin-sensitive IS volunteers
Participants in this randomized crossover trial will be admitted twice to the inpatient clinical research unit During each admission they will take a dose of either alpelisib or placebo in randomized order in the evening and receive infusions of 13C sodium acetate and 2H D-glucose to measure DNL and endogenous glucose production EGP respectively during an overnight fast DNL measurement will then continue during the following day during 8 hours of standardized mixed-meal feedings Blood will be drawn at defined intervals for determining levels of glucose insulin lipids including triglycerides and free fatty acids and tracertracee enrichments for the stable-isotope tracers There will be a 2-8-week hiatus for drug washout between the two inpatient study admissions
Participants in this randomized crossover trial will be admitted twice to the inpatient clinical research unit During each admission they will take a dose of either alpelisib or placebo in randomized order in the evening and receive infusions of 13C sodium acetate and 2H D-glucose to measure DNL and endogenous glucose production EGP respectively during an overnight fast DNL measurement will then continue during the following day during 8 hours of standardized mixed-meal feedings Blood will be drawn at defined intervals for determining levels of glucose insulin lipids including triglycerides and free fatty acids and tracertracee enrichments for the stable-isotope tracers There will be a 2-8-week hiatus for drug washout between the two inpatient study admissions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None