Mitochondrial Substrate Utilization in the Diabetic Human Heart

NCT05958706 | Recruiting

• 1 other identifier: 2022-1962
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes can lead to heart failure independently, but the underlying causes remain incompletely understood. The main aim of this study is to identify differential regulation of mitochondrial substrate utilization and complex activity in heart failure and type 2 diabetes mellitus (T2DM). For this, we will conduct a prospective, observational study to examine myocardial mitochondrial oxidative function and related metabolic parameters, gene expression, histological markers, and inflammation in cardiac tissue from patients with heart failure or patients after heart transplantation. We will further assess cardiac function using cardiac magnetic resonance imaging with and without stress protocols and magnetic resonance spectroscopy. Glycemic control/T2DM will be characterized by oral glucose tolerance tests. The results of this project will help to better understand the cellular mechanisms of the development of diabetic cardiomyopathy and contribute to the development of early diagnostic, as well as therapeutic approaches for the prevention and treatment of diabetic cardiomyopathy.

Conditions

Type2diabetes; Insulin Resistance; Diabetic Cardiomyopathies; Heart Failure; Mitochondrial Diseases

Keywords

mitochondrial function; respirometry; heart failure; type 2 diabetes mellitus; insulin resistance; mitochondrial disease; diabetic cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• Substrate-specific JVO2 of ventricular myocardial mitochondrial oxidative capacity

  measured in (pmol/s\*mg)

  at time of the endomyocardial biopsy procedure

Secondary Outcomes (10)

• Markers of cardiac function and structure

  1 day before or after endomyocardial biopsy

• Markers of cardiac function

  1 day before or after endomyocardial biopsy

• Cardiac substrate utilization

  1 day before or after endomyocardial biopsy

• Patterns in the myocardial transcriptome and systemic metabolome

  at time of the endomyocardial biopsy procedure

• non-fatal myocardial infarction

  up to 5 years (follow-up in clinical routine)

Study Arms (3)

patients with manifest heart failure

patients with manifest heart failure and T2DM or patients with manifest heart failure without T2DM

patients with terminal heart failure

patients with terminal heart failure and T2DM or patients with terminal heart failure without T2DM

patients after heart transplantation

patients after heart transplantation and T2DM or patients after heart transplantation without T2DM

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with heart failure with or without T2DM undergoing endomyocardial biopsy for clinical reasons (WP1), patients with terminal heart failure with or without T2DM undergoing left ventricular assist device surgery or heart transplantation (WP2), and patients after heart transplantation with and without T2DM undergoing endomyocardial biopsy for clinical reasons (post-transplant surveillance).

You may qualify if:

• Age ≥ 20 and ≤ 85 years
• Male and female patients with manifest heart failure (NYHA II-IV) and clinical indication for myocardial biopsy or after transplantation and clinical indication for myocardial biopsy with or without type II diabetes mellitus or terminal (NYHA IV) heart failure with or without type II diabetes mellitus.
• Written informed consent

You may not qualify if:

• Acute infectious diseases within the last 2 weeks before the examination
• Autoimmune diseases or acute immunocompromising diseases (leukocytes \< 5000/μl)
• Pregnancy
• Use of alcohol or drugs (addiction), psychiatric diseases
• Suspected or manifest AIDS (HIV); hepatitis B or C.
• Liver disease not attributed to the presence of nonalcoholic fatty liver hepatitis or congestive hepatopathy in heart failure
• Malignant cancer
• Lack of capacity to give informed consent or lack of consent to participate in the study
• For MRI study with drug stress: contraindications to the use of regadenoson, specifically: a) Hypersensitivity to the active ingredient or any of the other ingredients mentioned. b) Second- or third-degree atrioventricular (AV) block or sinus node dysfunction, unless these patients have a functioning pacemaker. c) Unstable angina that has not been stabilized with medication. d) Severe hypotension. e) Decompensated stages of heart failure.

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead

Study Sites (1)

University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine

Düsseldorf, 40225, Germany

RECRUITING

MeSH Terms

Conditions

Heart Failure; Insulin Resistance; Mitochondrial Diseases; Diabetic Cardiomyopathies; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Cardiomyopathies; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Malte Kelm, Prof.

  Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf

  STUDY CHAIR

• Elric Zweck, MD

  Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elric Zweck, MD

CONTACT

+492118118800; elric.zweck@med.uni-duesseldorf.de

Amin Polzin, MD

CONTACT

+49211811800; amin.polzin@med.uni-duesseldorf.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: July 25, 2023
• Study Start: December 1, 2021
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2035
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)