Ignite Creation Date:
2025-12-25 @ 12:54 AM
Ignite Modification Date:
2026-01-02 @ 6:16 PM
Study NCT ID:
NCT03502967
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2025-08-26
First Post:
2018-04-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Imaging of Traumatic Brain Injury Metabolism Using Hyperpolarized Carbon-13 Pyruvate
Sponsor:
University of Texas Southwestern Medical Center
Organization:
Study Overview
Official Title:
Imaging of Traumatic Brain Injury Metabolism Using Hyperpolarized Carbon-13 Pyruvate
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HPTBI
Brief 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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: