Hyperpolarized MRSI in Ischemic Heart Disease: A Metabolic Investigation of the Heart Muscle

NCT ID: NCT06054516

Last Updated: 2023-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

15 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-10-13

Study Completion Date

2025-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study aims to investigate the potential of using hyperpolarized \[1-13C\]-pyruvate magnetic resonance imaging (MRI) to assess metabolic alterations in patients with ischemic heart disease (IHD). Altered myocardial metabolism is recognized as a crucial factor in heart failure and IHD, and modulating cardiac metabolism offers a new approach to treatment. However, current diagnostic modalities use ionizing radiation and have shown limited prognostic value.

Hyperpolarization through dynamic nuclear polarization (DNP) enables highly sensitive in vivo detection of metabolic processes. Hyperpolarized \[1-13C\]-pyruvate allows visualization of glycolysis-related metabolism, providing insights into the breakdown of glucose and its derivatives. By using this technique, the study aims to differentiate viable from non-viable myocardium in patients with IHD.

The objectives include implementing hyperpolarized \[1-13C\]-pyruvate cardiac MRI to image metabolic flux in the human heart and investigating the potential of this method to distinguish viable from non-viable myocardium in patients with IHD. The study endpoints involve assessing metabolic flux through the pyruvate dehydrogenase complex (PDC) and analyzing ratios of different metabolites, which can indicate the extent of pyruvate oxidation and lactate production.

A cross-sectional study design involving patients with CHF and ischemic heart disease will be used. Patients will undergo hyperpolarized \[1-13C\]-pyruvate MRI, PET imaging, late gadolinium enhancement (LGE) MRI, and cardiac magnetic resonance imaging (CMR). The study will compare \[1-13C\]-pyruvate MRI findings with PET results, allowing for a correlation between metabolic data and traditional imaging techniques. This innovative approach could provide valuable insights into the metabolic changes associated with ischemic heart disease

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Ischemic Heart Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ischemic heart disease

13C-enriched pyruvate

Intervention Type DIAGNOSTIC_TEST

Before starting the hyperpolarization injection procedure, the patient will be scanned using the standard MR imaging defined in the clinical protocol and 13C prescriptions and a pre-scan will be completed. The clinical investigator will mount the administration syringe in the MR compatible power-injector with pre-adjusted injection volume calculated according to body weight (0.43 ml /kg bw). This setting is checked by the scanning operator and clinical investigator. The injection valve is set for agent delivery, and agent injected at a rate of 5 ml/s. The timings are monitored using a stopwatch on the SPINLAB. Following injection of hyperpolarized \[1-13C\]-Pyruvate , 20 ml of sterile saline in a separate syringe, already attached to the patient line, will be used to flush the IV line at the same injection rate (5 ml/s).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

13C-enriched pyruvate

Before starting the hyperpolarization injection procedure, the patient will be scanned using the standard MR imaging defined in the clinical protocol and 13C prescriptions and a pre-scan will be completed. The clinical investigator will mount the administration syringe in the MR compatible power-injector with pre-adjusted injection volume calculated according to body weight (0.43 ml /kg bw). This setting is checked by the scanning operator and clinical investigator. The injection valve is set for agent delivery, and agent injected at a rate of 5 ml/s. The timings are monitored using a stopwatch on the SPINLAB. Following injection of hyperpolarized \[1-13C\]-Pyruvate , 20 ml of sterile saline in a separate syringe, already attached to the patient line, will be used to flush the IV line at the same injection rate (5 ml/s).

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Chronic heart failure
* \>18 years of age
* Left ventricular Ejection Fraction (LVEF) of 10 - 60 %
* Adequate hematologic and organ function.
* Women who are not postmenopausal or surgically sterile must have a negative serum or urine pregnancy test performed at time of inclusion in the study.
* Safe and highly effective contraception must be used throughout the study meaning either hormonal anti-conception or an anti-fertility intrauterine device. If the partner is non fertile or the patient has no sexual activities, this is also accepted.
* Non-insulin dependent Diabetes mellitus is allowed
* Danish speaking
* Able and willing to comply after informed consent
* Ischemic heart disease and referral to viability testing at the Department of Clinical Physiology and Nuclear Medicine at Aarhus University Hospital.

Exclusion Criteria

* Not able or willing to receive heart failure therapy
* Patients not willing to participate
* Uncontrolled serious medical condition, such as uncontrolled heart disease, uncontrolled diabetes, intestinal obstruction, uncontrolled hypertension, or recent cerebral ischemia
* Estimated Glomerular Filtration Rate (eGFR) \<30 mL/min
* Insulin dependent Diabetes Mellitus
* Intolerance to Pyruvate
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Henrik Wiggers

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Henrik Wiggers

Professor, PhD, DMSc

Responsibility Role SPONSOR_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Aarhus University Hospital

Aarhus, Central Jutland, Denmark

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Denmark

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Niels A. Jespersen, MD

Role: CONTACT

+4522950990

Henrik Wiggers, Professor

Role: CONTACT

+4522753202

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Niels A. Jespersen, MD

Role: primary

+4522950990

Henrik Wiggers, Professor

Role: backup

+4522753202

References

Explore related publications, articles, or registry entries linked to this study.

Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007 Mar 15;356(11):1140-51. doi: 10.1056/NEJMra063052. No abstract available.

Reference Type BACKGROUND
PMID: 17360992 (View on PubMed)

Rider OJ, Tyler DJ. Clinical implications of cardiac hyperpolarized magnetic resonance imaging. J Cardiovasc Magn Reson. 2013 Oct 8;15(1):93. doi: 10.1186/1532-429X-15-93.

Reference Type BACKGROUND
PMID: 24103786 (View on PubMed)

Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K. Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10158-63. doi: 10.1073/pnas.1733835100. Epub 2003 Aug 20.

Reference Type BACKGROUND
PMID: 12930897 (View on PubMed)

Golman K, Petersson JS, Magnusson P, Johansson E, Akeson P, Chai CM, Hansson G, Mansson S. Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med. 2008 May;59(5):1005-13. doi: 10.1002/mrm.21460.

Reference Type BACKGROUND
PMID: 18429038 (View on PubMed)

Schroeder MA, Lau AZ, Chen AP, Gu Y, Nagendran J, Barry J, Hu X, Dyck JR, Tyler DJ, Clarke K, Connelly KA, Wright GA, Cunningham CH. Hyperpolarized (13)C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart. Eur J Heart Fail. 2013 Feb;15(2):130-40. doi: 10.1093/eurjhf/hfs192. Epub 2012 Dec 19.

Reference Type BACKGROUND
PMID: 23258802 (View on PubMed)

Cunningham CH, Lau JY, Chen AP, Geraghty BJ, Perks WJ, Roifman I, Wright GA, Connelly KA. Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience. Circ Res. 2016 Nov 11;119(11):1177-1182. doi: 10.1161/CIRCRESAHA.116.309769. Epub 2016 Sep 15.

Reference Type BACKGROUND
PMID: 27635086 (View on PubMed)

Hansen ESS, Tougaard RS, Norlinger TS, Mikkelsen E, Nielsen PM, Bertelsen LB, Botker HE, Jorgensen HS, Laustsen C. Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1-13 C]pyruvate study. NMR Biomed. 2017 Jun;30(6). doi: 10.1002/nbm.3702. Epub 2017 Feb 10.

Reference Type BACKGROUND
PMID: 28186677 (View on PubMed)

Apps A, Lau JYC, Miller JJJJ, Tyler A, Young LAJ, Lewis AJM, Barnes G, Trumper C, Neubauer S, Rider OJ, Tyler DJ. Proof-of-Principle Demonstration of Direct Metabolic Imaging Following Myocardial Infarction Using Hyperpolarized 13C CMR. JACC Cardiovasc Imaging. 2021 Jun;14(6):1285-1288. doi: 10.1016/j.jcmg.2020.12.023. Epub 2021 Feb 10. No abstract available.

Reference Type BACKGROUND
PMID: 33582059 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

65424

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.