Hyperpolarized Carbon-13 Pyruvate Imaging for Traumatic Brain Injury

(HPTBI Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Illicit drugs

Disqualifiers: Schizophrenia, Bipolar, Stroke, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to observe changes in brain energy use after a traumatic brain injury (TBI). The study examines two types of a special imaging agent, hyperpolarized pyruvate (specifically, Hyperpolarized [1-13C] Pyruvate and Hyperpolarized [2-13C] Pyruvate), to detect changes in brain energy processing. It aims to enhance brain scans for individuals who have experienced a TBI. This trial suits those who have had a TBI within the last 30 days and underwent a head CT scan upon hospital admission. As an Early Phase 1 trial, this research focuses on understanding how the imaging agents function in people, offering participants a chance to contribute to groundbreaking advancements in brain injury diagnostics.

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 using illicit drugs that alter brain function, you cannot participate in the trial.

What prior data suggests that hyperpolarized carbon-13 pyruvate imaging is safe for traumatic brain injury patients?

Research has shown that hyperpolarized [1-13C] pyruvate is promising as a safe imaging agent. Studies have tested its use in the brain after injuries and found it to be safe and well-tolerated. One study examined its use after head trauma and reported no major safety concerns.

Similarly, researchers have tested hyperpolarized [2-13C] pyruvate in healthy individuals and those with brain injuries, finding it safe in these groups. Safety data supports its use without significant risks.

As this is an early phase study, the primary focus is on the safety of these treatments. Early phase trials often identify serious issues, but findings so far suggest these treatments are safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using hyperpolarized carbon-13 pyruvate imaging for traumatic brain injury (TBI) because it offers a novel way to assess brain metabolism in real-time. Unlike current treatment options for TBI, which often focus on managing symptoms and preventing further injury, these hyperpolarized pyruvate compounds allow for a detailed view of metabolic changes in the brain during an MRI scan. This approach could lead to more precise and timely interventions by providing crucial insights into the brain's energy use after injury. The two types of hyperpolarized pyruvate, [1-13C] and [2-13C], offer slightly different views of metabolic pathways, potentially providing complementary information to better understand and treat TBI.

What evidence suggests that this trial's treatments could be effective for Traumatic Brain Injury?

This trial will compare two forms of hyperpolarized pyruvate imaging for traumatic brain injury. Research has shown that hyperpolarized [1-13C] pyruvate, which participants in this trial may receive, can help identify changes in brain activity after a traumatic brain injury (TBI). Studies have found that patients exhibit different pyruvate metabolism, which relates to how the brain uses energy. This imaging method might help detect and predict TBI outcomes that were previously overlooked.

Similarly, another form, hyperpolarized [2-13C] pyruvate, is also being tested in this trial. It showed promise in early research by helping observe how the brain responds to injury through tracking changes in metabolism. Early findings suggest this approach could improve understanding of how TBI affects brain function. Both methods aim to enhance brain injury imaging by highlighting changes in metabolism. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with a confirmed traumatic brain injury (TBI) based on specific criteria, including Glascow coma scale scores and CT scans. Participants must have had the injury within the last 30 days and be able to consent in English or Spanish. Excluded are those with non-TBI related brain abnormalities, metal in their head that affects MRI, severe mental health issues, drug influence at scanning time, or any MRI contraindications.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent

My traumatic brain injury happened less than 30 days ago.

You have a documented and confirmed traumatic brain injury with a Glasgow Coma Scale score of 10-15 or loss of consciousness for more than 10 minutes.

Exclusion Criteria

Any contraindication per MRI Screening Form including implants contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillator (ICD), claustrophobia

Medically unstable including heart failure, severe left ventricular outflow tract (LVOT) obstruction, unstable angina, pregnancy, lactating

Subjects who are receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Procedure

Participants undergo imaging with hyperpolarized [1-13C] and [2-13C] pyruvate to assess cerebral glycolysis and mitochondrial dysfunction

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized [1-13C] Pyruvate
• Hyperpolarized [2-13C] Pyruvate

Trial Overview The study tests how well hyperpolarized carbon-13 pyruvate compounds work as imaging agents to show changes in brain metabolism after TBI. It aims to assess mitochondrial dysfunction and cerebral glycolysis using advanced imaging techniques in patients who've recently suffered from TBI.

How Is the Trial Designed?

Group I: Hyperpolarized [2-13C] Pyruvate Experimental Treatment 1 Intervention

Injection with hyperpolarized \[2-13C\] Pyruvate during MRI.

Group II: Hyperpolarized [1-13C] Pyruvate Experimental Treatment 1 Intervention

Injection with hyperpolarized \[1-13C\] Pyruvate during MRI.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

A new method for normalizing hyperpolarized [1-13 C]pyruvate MRI signals using expired 13 CO2 significantly reduces variability in metabolic measurements, improving the accuracy of metabolic imaging in clinical settings.

In a study involving 11 pigs with induced renal hypoperfusion, this normalization technique led to a 25% reduction in variance for certain metabolic ratios, enhancing the specificity of the imaging results without significantly affecting other ratios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considering whole-body metabolism in hyperpolarized MRI through 13 C breath analysis-An alternative way to quantification and normalization? Sejersen, S., Rasmussen, CW., Bøgh, N., et al.[2023]

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]

Using multi-resolution hyperpolarized 13C pyruvate MRI in 6 subjects improved the measurement of kinetic conversion rates in the human brain, particularly by enhancing spatial resolution and reducing partial volume effects.

Higher resolution images (7.5 × 7.5 mm2) led to more accurate calculations of pyruvate-to-lactate conversion rates, especially in areas near blood vessels, indicating that finer resolution can significantly enhance metabolic data quality in brain imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism. Hu, JY., Kim, Y., Autry, AW., et al.[2023]

The study monitored mitochondrial metabolism in male Wistar rats after traumatic brain injury (TBI) by measuring [13C]bicarbonate production from hyperpolarized [1-13C]pyruvate, revealing significantly reduced bicarbonate levels at the injury site, indicating impaired mitochondrial function.

Bicarbonate production peaked at 24 hours post-injury and returned to normal by day 10, suggesting that [13C]bicarbonate could serve as a sensitive in-vivo biomarker for assessing secondary injury processes following TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of mitochondrial dysfunction in acute traumatic brain injury using hyperpolarized [1-13 C]pyruvate. Hackett, EP., Chen, J., Ingle, L., et al.[2023]

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]

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 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7736977/

Imaging Acute Metabolic Changes in Patients with Mild ... Patients were imaged with hyperpolarized [1-13C]pyruvate MRSI 1 or 6 days after head trauma. Both patients showed significantly reduced ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06103201

Hyperpolarized 13C-pyruvate Metabolic MRI With ... The purpose of this study is to examine the safety and feasibility of using hyperpolarized metabolic MRI to study early brain metabolism changes.

3. elifesciences.org elifesciences.org/reviewed-preprints/106736

Hyperpolarized 13 C metabolic imaging detects long ... This study presents a valuable finding on the perturbed pyruvate metabolism in models of repetitive traumatic brain injury.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10462249/

Hyperpolarized 13C metabolic imaging detects long- ... Our study demonstrates the potential of metabolic imaging to improve detection, classification and outcome prediction of previously undetected rTBI.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03502967

Imaging of Traumatic Brain Injury Metabolism Using ... This project is to evaluate sensitivity and specificity of hyperpolarized 13C-pyruvate as imaging agents of altered cerebral glycolysis and mitochondrial ...

6. nature.com nature.com/articles/s41598-017-17758-4

In vivo metabolic imaging of Traumatic Brain Injury Our results demonstrate that HP [1- 13 C] pyruvate has great potential for in vivo non-invasive detection of cerebral metabolism post-TBI.

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

Hyperpolarized Pyruvate (13C) Injection Imaging of Traumatic Brain Injury. Metabolism Using Hyperpolarized Carbon-. 13 ... was stated as one of the likely key mechanisms of ischemic brain injury.