Pyruvate Imaging for High Blood Pressure

Recruiting at 1 trial location

Overseen By Nadia Bragagnolo, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Claustrophobia, Low hemoglobin, Low GFR, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

112 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to better understand heart conditions like congestive heart failure (CHF). It uses a special MRI technique to create detailed pictures of heart cells' activity with hyperpolarized pyruvate, a type of contrast agent. The goal is to enhance how doctors see and manage heart issues. The trial seeks healthy volunteers and individuals with high blood pressure, heart muscle thickening, or stable heart failure. Participants should be able to identify if they have these conditions or have type 2 diabetes managed by oral medication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking investigational drugs, you must not have received them within 1 month before or after joining the study.

What prior data suggests that this imaging method is safe for humans?

Research has shown that the Hyperpolarized (13C) Pyruvate Injection is generally safe and well-tolerated. In one study, some participants reported a sweet taste after the injection, which quickly subsided. Importantly, no serious side effects occurred. Another study observed a drop in blood pressure after the injection, but the significance of this remains unclear. Overall, while minor effects exist, the treatment appears safe for humans so far. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel imaging technique using hyperpolarized (13C) pyruvate to study high blood pressure and related heart conditions. Unlike conventional imaging methods, this technique aims to provide real-time insights into heart metabolism, potentially offering a clearer picture of how high blood pressure affects heart function. This could lead to more precise diagnoses and tailored treatments, improving patient outcomes. By focusing on metabolic changes, this approach might unveil new aspects of heart disease that current methods overlook, paving the way for innovative therapeutic strategies.

What evidence suggests that this trial's imaging methods could be effective for managing congestive heart failure?

Research has shown that Hyperpolarized Carbon-13 Pyruvate Injection, which participants in this trial may receive, effectively and safely studies how the body manages diseases like heart failure. This technique uses a special MRI scan to examine how the heart uses energy. Studies indicate that this method can detect changes in energy use in heart failure patients, potentially aiding doctors in better managing the condition. Although still under investigation, this treatment has shown promise in providing doctors with detailed insights into heart health without invasive procedures. ^{1 2 4 5 6}

Who Is on the Research Team?

Charles Cunningham, PhD

Principal Investigator

Sunnybrook Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with heart enlargement or high blood pressure. Participants aged 19-50 and 30-75 are needed, depending on the group they fall into. They must have specific heart conditions like left-ventricular hypertrophy, diagnosed cardiomyopathy, stable heart failure with elevated LV mass, or type 2 diabetes with controlled HcA1c levels.

Inclusion Criteria

Written consent

Age: 19 to 50 in Arm 1, 30 to 75 in Arm 2

Group 2A and 2E participants have left-ventricular hypertrophy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Procedure

Participants undergo metabolic imaging of the heart using Hyperpolarized Pyruvate 13C Injection and standard cardiovascular MRI workup

Single visit, approximately 3 hours

1 visit (in-person)

Follow-up

Participants receive a follow-up telephone call to ascertain any study-related adverse events

1 week

1 call (virtual)

Long-term Follow-up

The entire study is expected to take about 3 years, with results known approximately six months after study completion

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Gadolinium
• Hyperpolarized (13C) Pyruvate Injection

Trial Overview The study tests a new MRI method using Hyperpolarized (13C) Pyruvate Injection to improve imaging of the cardiovascular system in patients with congestive heart failure. This could help doctors better manage CHF by visualizing biochemical reactions in heart cells more clearly.

How Is the Trial Designed?

Group I: Hypertension Hypertrophy Volunteers Experimental Treatment 2 Interventions

Arm 2 * Group 2A: patients aged 30 to 75 with hypertension and hypertrophy * Group 2B: patients aged 30 to 75 with non-obstructive hypertrophic cardiomyopathy (HCM). * Group 2C: stable outpatients with NYHA class 1-3 heart failure who have evidence of elevated LV mass (LVH), irrespective of LVEF. * Group 2D: stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents. * Group 2E: patients aged 30 to 75 with hypertrophy * Group 2F: patients aged 30 to 75 with hypertrophic cardiomyopathy (HCM). * Group 2G: stable outpatients with NYHA class 1-3 heart failure who have evidence of elevated LV mass (LVH), irrespective of LVEF. * Group 2H: stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents.

Group II: Healthy Volunteers Experimental Treatment 1 Intervention

Arm 1 * Group 1A: control male volunteers between 19 and 50 years of age. * Group 1B: control female volunteers between 19 and 50 years of age. * Group 1C: control male or female volunteers between 19 and 50 years of age, with the MRI scan performed twice * Group 1D: control male volunteers between 19 and 50 years of age. * Group 1E: control female volunteers between 19 and 50 years of age. * Group 1F: control male or female volunteers between 19 and 50 years of age, with the MRI scan performed twice

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

The study successfully measured in vivo cardiac T2∗ values of hyperpolarized [1-13 C]pyruvate and its metabolites in both rodents and humans, demonstrating the effectiveness of a new imaging technique that can capture cardiac metabolism noninvasively.

In humans, T2∗ values for [1-13 C]pyruvate were significantly higher in the ventricles (108.7 ms in the left and 129.4 ms in the right) compared to rodents, indicating differences in cardiac metabolism that could be important for future research and clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

>Cardiac T2∗ measurement of hyperpolarized 13 C metabolites using metabolite-selective multi-echo spiral imaging. Ma, J., Chen, J., Reed, GD., et al.[2022]

High-resolution hyperpolarized 13C pyruvate MRI can effectively measure cerebral perfusion in the human brain, showing significant positive correlations with traditional arterial spin labeling (ASL) methods across different brain regions.

This study, involving five healthy volunteers, demonstrates that hyperpolarized pyruvate MRI not only provides detailed spatial imaging of brain structures but also allows for simultaneous assessment of cerebral metabolism and perfusion, enhancing our understanding of brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating cerebral perfusion with high resolution hyperpolarized [1-13 C]pyruvate MRI. Hu, JY., Vaziri, S., Bøgh, N., et al.[2023]

Hyperpolarized (HP) (13)C labeled compounds, particularly HP 1-(13)C pyruvate, are effective MR contrast agents that allow for real-time investigation of metabolic pathways in vivo, with the ability to track pyruvate metabolism for nearly 2 minutes post-injection.

The technique has expanded beyond tumor metabolism to non-invasively assess physiological parameters like pH, highlighting its growing potential in medical research, especially with the increasing availability of dynamic nuclear polarization (DNP) systems for generating hyperpolarized materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13carbon MR. Rowland, IJ., Peterson, ET., Gordon, JW., et al.[2019]

A new hyperpolarization technique using parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) can produce highly hyperpolarized [1-13 C]pyruvate solutions quickly and efficiently, achieving concentrations of 70-160 mM in just 85 seconds.

In a study with 48 animals, the safety and image quality of PHIP-SAH were found to be comparable to the established dissolution dynamic nuclear polarization (d-DNP) method, suggesting that PHIP-SAH could be a practical alternative for metabolic MRI applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parahydrogen-Polarized [1-13 C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging. Nagel, L., Gierse, M., Gottwald, W., et al.[2023]

Hyperpolarized [1-13 C]pyruvate imaging is a feasible and reproducible technique for studying cardiac metabolism in large animal models, showing no adverse effects on blood pressure or ejection fraction during the study.

Infusion of glucose-insulin-potassium (GIK) enhances the conversion of pyruvate to metabolic products like lactate, alanine, and bicarbonate, although this process exhibited increased variability, indicating potential challenges in consistent metabolic modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1-13 C]pyruvate study. Hansen, ESS., Tougaard, RS., Nørlinger, TS., et al.[2018]

A stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate was successfully developed, allowing for its use in metabolic imaging studies.

In a study involving anesthetized rats, hyperpolarized [1-(13)C]-ethyl pyruvate was compared to [1-(13)C]-pyruvate, demonstrating its potential for effective uptake and metabolic imaging in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. Hurd, RE., Yen, YF., Mayer, D., et al.[2021]

Hyperpolarized carbon-13 (13C) MRI is a groundbreaking imaging technique that allows for real-time, noninvasive observation of metabolic processes in diseases like cancer and cardiovascular conditions, which were previously difficult to study.

The review highlights the promising clinical applications of HP [1-13C]pyruvate MRI, suggesting it could enhance our understanding of metabolism, improve disease diagnosis, and speed up treatment evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MRI: State of the Art and Future Directions. Wang, ZJ., Ohliger, MA., Larson, PEZ., et al.[2020]

The study successfully developed methods to prepare hyperpolarized [2-13C]pyruvate for the first human NMR studies, demonstrating its feasibility for investigating brain energy metabolism in four healthy volunteers.

Results showed that the conversion of hyperpolarized [2-13C]pyruvate to [2-13C]lactate and [5-13C]glutamate can be measured, with conversion rates comparable to previous studies using [1-13C]pyruvate, indicating the potential for this technique in metabolic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism. Chung, BT., Chen, HY., Gordon, J., et al.[2022]

This study demonstrates that using (13)C hyperpolarization enhanced MRI is a feasible method for monitoring pyruvate metabolism in the heart during ischemic episodes, allowing for real-time visualization of metabolite concentrations.

In pigs subjected to 15 and 45 minutes of artery occlusion, significant changes in bicarbonate and alanine levels were observed, indicating that this imaging technique can effectively detect metabolic alterations associated with heart ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Golman, K., Petersson, JS., Magnusson, P., et al.[2015]

The study successfully synthesized various hyperpolarized 1-13C-acetates and 1-13C-pyruvates, which can be used as effective contrast agents for molecular imaging, achieving yields of up to 70%.

Using a method called parahydrogen-induced polarization (PHIP), the researchers demonstrated that hyperpolarized 1-13C-pyruvate can be produced with a polarization of approximately 3.2%, enabling enhanced imaging capabilities in 13C magnetic resonance imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of Unsaturated Precursors for Parahydrogen-Induced Polarization and Molecular Imaging of 1-13C-Acetates and 1-13C-Pyruvates via Side Arm Hydrogenation. Chukanov, NV., Salnikov, OG., Shchepin, RV., et al.[2020]

Using hyperpolarized [1-(13)C]alanine allows for more accurate measurement of intracellular lactate-to-pyruvate ratios in vivo, showing a ratio of 4.89±0.61 in normal rat tissue, compared to a misleading ratio of 0.41±0.03 when using [1-(13)C]pyruvate.

This study highlights the limitations of using [1-(13)C]pyruvate for metabolic imaging, as it does not accurately reflect intracellular levels due to its extracellular presence, emphasizing the need for alternative agents like [1-(13)C]alanine for better insights into cellular metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine. Hu, S., Zhu, M., Yoshihara, HA., et al.[2021]

This study demonstrates the successful use of hyperpolarized 13C spectroscopy to detect metabolic products in the rat brain, specifically identifying [1-(13)C]lactate and [13C]bicarbonate after injecting [1-(13)C]pyruvate.

The research highlights the potential of using hyperpolarized [2-(13)C]pyruvate to detect [2-(13)C]lactate, although it did not reveal other metabolites, indicating that different pyruvate isotopes can yield varying insights into metabolic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo 13C spectroscopy in the rat brain using hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate. Marjańska, M., Iltis, I., Shestov, AA., et al.[2021]

Citations

1. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/13c-pyruvate-ib.pdf

Hyperpolarized Pyruvate (13C) Injection A drop in arterial blood pressure was observed after pyruvate injections. Data from administration of hypertonic and isotonic test item indicate that the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6490043/

Hyperpolarized 13C MRI: State of the Art and Future Directions Hyperpolarized carbon 13 MRI is an emerging molecular imaging technique that is actively undergoing clinical translation at multiple institutions.

3. withpower.com withpower.com/trial/phase-1-hypertrophy-3-2016-a5ea2

Pyruvate Imaging for High Blood Pressure Research shows that Hyperpolarized Carbon-13 Pyruvate Injection is effective in rapidly and non-invasively investigating metabolic processes in diseases like ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1097664724011220

13 C]pyruvate cardiovascular magnetic resonance imaging ... This study highlighted the ability of HP [1- 13 C]pyruvate CMR to detect changes in metabolism in HF. HP [1- 13 C]pyruvate CMR has the potential for metabolic ...

5. ahajournals.org ahajournals.org/doi/10.1161/circresaha.116.309769

Hyperpolarized 13C Metabolic MRI of the Human Heart During injection, there was no change in heart rate and no reported change in respiration. Noninvasive blood pressure measured before the CMR ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02648009

Metabolic Imaging of the Heart Using Hyperpolarized (13C ... For this study, the heart of control subjects and those with hypertension or hypertrophy will be imaged using Hyperpolarized Pyruvate 13C Injection. Different ...