Clinical Trial: Diabetic Cardiomyopathy and Heart Failure

Study Status: NOT_YET_RECRUITING
Recruit Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL

Official Title: Preventing Diabetic Cardiomyopathy and Heart Failure by Ketone Bodies

Brief Summary: This study will demonstrate the beneficial effects of ketone bodies in type 1 diabetes (T1D) patients and will have significant translational applications to prevent serious metabolic conditions such as T1D induced diabetic cardiomyopathy (DCM).

Detailed Summary: T1D remains the primary cause of DCM.
The long-term goal is to understand the mechanism of T1D leading to DCM.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in degrading the low-density lipoprotein receptors (LDLRs) and that increases the circulating LDL cholesterol (LDL-C).
Further, PCSK9 increases duringT1D and that, in turn, decreases mitochondrial bioenergetics, transcription factor- mitochondrial (TFAM), and the mitochondrial numbers thus creates an oxidative stress.
These changes lead to oxidation of high-density lipoprotein paraoxonase-1 (HDL-Pon1).
Because Pon1 hydrolyzes homocysteine (Hcy), the oxidized Pon1 thus causes accumulation of Hcy (i.e.
hyperhomocysteinemia; HHcy).
Also, the 'metabolic memory' is associated with epigenetic modification (methylation) of genes encoding proteins such as thioredoxin interacting protein (TXNIP).
Since methylation/epigenetics inhibits genes, this phenomenon generates even more amounts of Hcy.
Investigators have shown that HHcy decreases G-protein coupled receptor (GPCR) G?s subunit, protein kinase-B (AKT), focal adhesion kinase (FAK) but increases calpain-1, inflammasome and oxidative stress.
The central hypothesis is that an increase in PCSK9 causes oxidative stress and decreases TXNIP thus causing oxidation of HDL-Pon1 and subsequent accumulation of Hcy.
These alterations lead to decrease in G?s, AKT, FAK and concomitant increase in PCSK9 and calpain-1 causing metabolic, diastolic, and systolic cardiac dysfunction.
Treatment with ketone bodies (the food for mitochondria) will mitigate these changes.
Sponsor: Mahavir Singh, DVM, MS, PhD

Current Primary Outcome: Levels of glucose in blood and urine

Original Primary Outcome: Levels of glucose in blood and urine

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Louisville

Dates:
Date Received: September 16, 2022
Date Started: July 01, 2023
Date Completion: July 01, 2023
Last Updated: October 05, 2022
Last Verified: October 01, 2022