Diabetic Cardiomyopathy and Heart Failure

Heart Failure Clinical Trial

Official title:

Preventing Diabetic Cardiomyopathy and Heart Failure by Ketone Bodies

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05571865
• Other study ID #: 00002
• Secondary ID: PA-20-190
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2023
• Est. completion date: June 2026

Study information

• Verified date: October 2022
• Source: University of Louisville
• Contact: Mahavir Singh, DVM, MS, PhD
• Phone: (502) 403-4125
• Email: mahavir.singh[@]louisville.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

-Diabetic subjects with high blood glucose levels

Exclusion Criteria:

• Comorbidities affecting glucose levels and cardiac function

Related Conditions & MeSH terms

• Cardiomyopathies
• Diabetic Cardiomyopathies
• Heart Failure

Intervention

Dietary Supplement:
• Probiotic
Oral administration of a probiotic

Locations

Country	Name	City	State
United States	University of Louisville School of Medicine	Louisville	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Mahavir Singh, DVM, MS, PhD	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Mishra SP, Wang S, Nagpal R, Miller B, Singh R, Taraphder S, Yadav H. Probiotics and Prebiotics for the Amelioration of Type 1 Diabetes: Present and Future Perspectives. Microorganisms. 2019 Mar 2;7(3). pii: E67. doi: 10.3390/microorganisms7030067. Review — View Citation

Wang CH, Yen HR, Lu WL, Ho HH, Lin WY, Kuo YW, Huang YY, Tsai SY, Lin HC. Adjuvant Probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammato — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Outcome Measure-I	Levels of glucose in blood and urine	4 years
Primary	Primary Outcome Measure-II	Cardiac function evaluation by electrocardiogram	4 years
Secondary	Secondary Outcome Measure-I	Biochemical estimation of biomarkers from blood samples	4 years