Diabetic Cardiomyopathy and Heart Failure

January 28, 2025 updated by: University of Louisville

Preventing Diabetic Cardiomyopathy and Heart Failure by Ketone Bodies

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).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

-Diabetic subjects with high blood glucose levels

Exclusion Criteria:

- Comorbidities affecting glucose levels and cardiac function

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Control subjects (non-diabetic).

Control subjects (non-diabetic):

10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic)
Dietary supplement: Probiotic
Oral administration of a probiotic
Other: Diabetic Subjects

Diabetic subjects:

10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic)
Dietary supplement: Probiotic
Oral administration of a probiotic

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Outcome Measure-I
Time Frame: 4 years
Biochemical estimation of biomarkers from blood samples
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Louisville

Collaborators

National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Mahavir Singh, DVM, MS, PhD, University of Louisville School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2025

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

September 16, 2022

First Submitted That Met QC Criteria

October 5, 2022

First Posted (Actual)

October 7, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 28, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00002
  • PA-20-190 (Other Identifier: NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Outcomes of the probiotic intervention in diabetic patients for the prevention of cardiomyopathy.

IPD Sharing Time Frame

As soon as the data is collected, and fully analyzed.

IPD Sharing Access Criteria

Via personal meetings, national and international conferences.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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