Diabetic Cardiomyopathy and Heart Failure

Not Applicable

Withdrawn

• Conditions: Heart Failure; Diabetic Cardiomyopathies
• Interventions: Dietary Supplement: Probiotic

• Registration Number: NCT05571865
• Lead Sponsor: University of Louisville

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 Description

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) Gαs 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 Gαs, 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.

Study Timeline

• Study First Submitted: 2022-09-16
• Study First Submitted QC: 2022-10-05
• Study First Posted: 2022-10-07
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-28
• Last Update Posted: 2025-01-31
• Study Start: 2025-07
• Primary Completion: 2026-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

-Diabetic subjects with high blood glucose levels

Exclusion Criteria

• Comorbidities affecting glucose levels and cardiac function

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Diabetic Subjects	Probiotic	Diabetic subjects: 10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic)
Control subjects (non-diabetic).	Probiotic	Control subjects (non-diabetic): 10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic)

Primary Outcome Measures

Name	Time	Method
Primary Outcome Measure-II	4 years	Cardiac function evaluation by electrocardiogram
Primary Outcome Measure-I	4 years	Levels of glucose in blood and urine

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome Measure-I	4 years	Biochemical estimation of biomarkers from blood samples

Trial Locations

Locations (1)

University of Louisville School of Medicine; 🇺🇸 Louisville, Kentucky, United States