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

Official 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.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 40 participants

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 In \[1-13C\] pyruvate, the C-1 carbonyl has been replaced by a 13C-nucleus.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
• DEVICE: MRI Scanner — MRI Brain scan

Primary Outcomes

• To determine the percent changes in MS lesions, white matter, and whole brain HP 13C pyruvate metabolism measures between the pre-treatment scan and the scan obtained 1.5-months following treatment initiation. (From study initiation to up to 15 months after enrollment of last subject.)

Secondary Outcomes

• To determine the percent changes in MS lesions, white matter, and whole brain HP 13C pyruvate metabolism measures between the pre-treatment scan and the scan obtained 3-months and one year following treatment initiation. (From study initiation to up to 15 months after enrollment of last subject.)
• To determine the repeatability of HP 13C pyruvate metabolism measures in the MS lesions in patients with same-day repeated dose. (From study initiation to 15 months after enrollment of last subject.)
• To determine the repeatability of HP 13C pyruvate metabolism measures in the MS lesions in patients with same-day repeated dose. (From study initiation to 15 months after enrollment of last subject.)

Trial Locations

• Byers Hall, San Francisco, California, United States

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