Hyperpolarized Carbon Imaging for Multiple Sclerosis

(MIIMS Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ari Green

Must be taking: Anti-CD20 therapy

Must not be taking: Corticosteroids

Disqualifiers: Pregnancy, Hypertension, Heart failure, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

Ari Green, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Inclusion Criteria

Patients enrolled will be screened for at least one MS lesion with a 10mm diameter in one plane.

I am 18 years old or older.

I have relapsing remitting MS and haven't used disease-modifying drugs for at least 2 years.

Exclusion Criteria

Breastfeeding/chestfeeding individuals.

My EDSS score is higher than 6.5.

I have taken corticosteroids in the past 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Optimization

8 patients will be imaged once to optimize HP 13C MR parameters for improved spatial and temporal resolution

1 session

1 visit (in-person)

Baseline Imaging

32 RRMS patients will undergo a baseline anatomic and HP 13C pyruvate MRI scan prior to receiving treatment

1 session

1 visit (in-person)

Treatment and Monitoring

Participants will undergo two more HP 13C pyruvate MRI scans and one standard MRI over the span of approximately one year

12 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• HP 13C pyruvate injection

How Is the Trial Designed?

Group I: HP13C MRI Experimental Treatment 2 Interventions

8 patients will be imaged once to optimize HP 13C MR parameters for improved spatial and temporal resolution. This group will receive HP 13C pyruvate injection at a dosage of 0.43 mL/kg body weight. 32 RRMS patients who will undergo anatomic and HP 13C pyruvate MRI scans at timepoints of baseline, 1.5 months, 3 months, 12 months. This group will receive HP 13C pyruvate injection at a dosage of 0.43 mL/kg body weight.

Who Is Running the Clinical Trial?

Ari Green

Lead Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+