Hyperpolarized Carbon Metabolic Imaging in Multiple Sclerosis

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.

Conditions

• Multiple Sclerosis
• RRMS
• Relapsing Remitting MS

Interventions

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 In \[1-13C\] pyruvate, the C-1 carbonyl has been replaced by a 13C-nucleus.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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• Ari Green

  lead OTHER

Principal Investigators

• Ari Green, MD · University of California, San Francisco

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-04-01

Primary Completion

2029-12-01

Completion

2029-12-01

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations