NCT03502967

Imaging of Traumatic Brain Injury Metabolism Using Hyperpolarized Carbon-13 Pyruvate

• Status: Enrolling By Invitation
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

This project is to evaluate sensitivity and specificity of hyperpolarized 13C-pyruvate as imaging agents of altered cerebral glycolysis and mitochondrial dysfunction and assess pyruvate utilization in mitochondria in Traumatic Brain Injury (TBI) patients.

Detailed description

Aim 1: Investigators will quantify changes in \[1-13C\]lactate and H13CO3- labeling following a bolus injection of hyperpolarized \[1-13C\]pyruvate during the time window of secondary injury to assess upregulated glycolysis. Due to heterogeneous presence and severity of damage by TBI, defining the injured brain region can be difficult. Therefore, the metabolite ratio maps (\[product\]/\[pyruvate\]) of TBI patients (n = 5) will be compared with those of healthy-controls (n = 3). Hyperpolarized \[2-13C\]pyruvate will be examined in a separate group of TBI cohorts (n = 5) and healthy controls (n = 3), and \[5-13C\]glutamate, \[1-13C\]acetyl-carnitine, \[1-13C\]acetoacetate, and \[1-13C\]citrate from \[2-13C\]pyruvate will be quantified for assessing the altered mitochondrial metabolism. Imaging procedure with \[2-13C\]pyruvate is the same as the imaging with hyperpolarized \[1-13C\]pyruvate. For both \[1-13C\]pyruvate and \[2-13C\]pyruvate studies, each subject will be imaged twice with a 45min interval for confirming the reproducibility of the methods and/or averaging to enhance the signal-to-noise ratios of 13C-metabolite maps. Aim 2: After the feasibility study (aim1) is completed, an intra-subject comparison study of \[1-13C\]pyruvate and \[2-13C\]pyruvate will be performed. Similar to the aim1, patients with post-TBI neurological disorders having normal or near-normal CT results (n = 6 patients) as well as normal brains of age/gender-matching healthy volunteers (n = 3) will be recruited. Each patient will be imaged twice (one with \[1-13C\]pyruvate and one with \[2-13C\]pyruvate with a 45min interval). PDH activity and the TCA cycling will be assessed from measured H13CO3- from hyperpolarized \[1-13C\]pyruvate and \[5-13C\]glutamate from \[2-13C\]pyruvate, respectively. The comparison of \[1-13C\]pyruvate and \[2-13C\]pyruvate will identify the detailed information of how pyruvate (and converted acetyl-CoA) is utilized in the mitochondria, and assess the utility and necessity of imaging hyperpolarized \[2-13C\]pyruvate in TBI, providing critical data for future grant applications and larger clinical trials.

Conditions

• Traumatic Brain Injury

Interventions

Type	Name	Description
DRUG	Hyperpolarized [1-13C] Pyruvate	Bolus injection of study drug
DRUG	Hyperpolarized [2-13C] Pyruvate	Bolus injection of study drug

Timeline

• Start date: 2018-06-01
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2018-04-19
• Last updated: 2025-08-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study