NCT07510607

Hyperpolarized Carbon Metabolic Imaging in Multiple Sclerosis

Assessing Metabolic Changes in Multiple Sclerosis Using Hyper-polarized Carbon 13 MRI

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Ari Green · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The main purpose of this study is to assess whether hyperpolarized carbon imaging in relapsing remitting multiple sclerosis (MS) patients can be used to predict response to anti-CD20 disease modifying therapy. Study procedures will include magnetic resonance imaging (MRI) assessments with a hyperpolarized pyruvate sequence, clinical assessment as well as blood markers of disease progression. This method of imaging utilizes the Warburg effect, where innate immune cells utilize a metabolic shift to glycolysis instead of oxidative phosphorylation. In pre-clinical data, increased hyperpolarized lactate production has been found to be associated with increased microglial/macrophage infiltration in the brain. Although hyperpolarized carbon imaging in humans has been established and used in the field of oncology, this will be one of the first applications of hyperpolarized carbon the study of neuroinflammation in humans. We predict that hyperpolarized carbon imaging may have the potential to monitor and evaluate neuroinflammation in MS, and in particular the innate immune activation state that plays a role in MS progression. This imaging method may provide non-invasive monitoring of disease progression and therapy response for MS patients.

Detailed description

This is a prospective investigational study to evaluate the utility of HP 13C pyruvate MRI for assessing metabolism in MS lesions and monitoring response to treatment. A total of 40 relapse-remitting (RRMS) patients naïve to DMT and starting on an anti-CD20 therapy as part of their routine MS clinical care will be recruited. In a preliminary cohort, 8 patients will be imaged once to optimize HP 13C MR parameters for improved spatial and temporal resolution. Using these sequence parameters, we will then image 32 RRMS patients who will undergo a baseline anatomic and HP 13C pyruvate MRI scan prior to receiving treatment. These participants will undergo two more HP 13C pyruvate MRI scans and one standard MRI over the span of approximately one year. Participants will have blood draws for blood-based biomarkers of disease activity and will undergo standard MS clinical assessments. Multiple Sclerosis (MS) is the most prevalent chronic inflammatory disease of the central nervous system (CNS) among adults, characterized by demyelinating lesions linked to motor and cognitive impairments and permanent disabilities. Presently, MRI is used to assess active/inactive CNS lesions. Although informative for diagnosis, such measures do not correlate well with clinical symptoms or with MS progression. Given the importance of inflammation and oxidative stress in MS1, new non-ionizing imaging methods providing insights on these pathogenic processes would improve patient management and treatment. Hyperpolarization increases the MR signal of 13C probes by \>50,000, overcoming the inherently limited sensitivity of endogenous 13C and enables the monitoring of metabolic reactions in the brain in real time in vivo. HP 13C MR was first developed for oncology2,3, and in the last decade, has improved the non-invasive detection of neoplasms through monitoring of increased HP \[1-13C\]pyruvate to lactate conversion in preclinical models and in the clinic.4-6 A phase I study to assess the safety and tolerability of HP 13C pyruvate injection in healthy volunteers was completed in December 2007, as well as a second safety study in patients over the age of 60 with the majority of subjects tolerating the injection well and the only serious adverse effect being "flushing" with changes in systolic and diastolic blood pressure, thought to be secondary to a baroreflex response. Throughout the study, data on serum biochemistry variables and post-dosing changes were unremarkable, and no notable changes in vital signs, hematology, urinalysis, electrocardiogram (EKG) variables or other safety variables were registered. This has further been validated in men with localized prostate cancer in a UCSF phase I study. In the present study, each subject will receive HP 13C pyruvate injection at a dosage of 0.43 mL/kg body weight, which was the administered dose in the prior UCSF phase I study in prostate cancer (NCT01229618). Over 1,000 patients have been safely scanned with HP 13C pyruvate injection before March 2026.

Conditions

• Multiple Sclerosis
• RRMS
• Relapsing Remitting MS

Interventions

Type	Name	Description
DRUG	HP 13C pyruvate injection	Each participant will receive HP 13C pyruvate injection at a dosage of 0.43 mL/kg body weight during the MRI scan. A subset of subjects will undergo a repeatability study with a second HP 13C pyruvate injection at the same dosage. 13C is a stable, non-radioactive isotope of carbon with approximately 1% natural abundance. \[1-13C\] pyruvate has the same chemical characteristics as pyruvate. In \[1-13C\] pyruvate, the C-1 carbonyl has been replaced by a 13C-nucleus. These enriched isotopes have a magnetic moment and can be hyperpolarized in the presence of an EPA, i.e., AH111501 sodium salt (a stable trityl radical) by dynamic nuclear polarization (DNP) technique. As \[1-13C\] pyruvate has the same chemical characteristics as pyruvate, it is metabolized the same way. The polarization procedure allows MR imaging to rapidly detect the hyperpolarized 13C-label in \[1-13C\] pyruvate and its metabolites, \[1-13C\] lactate, \[1-13C\] alanine, and \[13C\] bicarbonate.
DEVICE	MRI Scanner	MRI Brain scan

Timeline

• Start date: 2026-04-01
• Primary completion: 2029-12-01
• Completion: 2029-12-01
• First posted: 2026-04-03
• Last updated: 2026-04-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study