NCT07510607 · Ari Green
Hyperpolarized Carbon Metabolic Imaging in Multiple Sclerosis
(MIIMS)
What this study is about
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.
View original scientific description
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.
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 In \[1-13C\] pyruvate, the C-1 carbonyl has been replaced by a 13C-nucleus.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
Primary outcome measures
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.
Time frame: From study initiation to up to 15 months after enrollment of last subject.
Percent changes in lesion HP 13C pyruvate metabolism measures. The following metabolism measures will be assessed at baseline and at 1.5-months following treatment initiation * Peak HP 13C lactate/pyruvate and bicarbonate/pyruvate signal-to-noise ratio * HP 13C lactate/pyruvate and bicarbonate/pyruvate AUC ratio * Metabolic rate constants kPL and kPB in inverse seconds.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Subjects must be 18 years or older.
- Relapsing remitting MS, naïve to DMTs for the past two years minimum
- Patients must be naive to anti-CD20 therapy with plans to begin the therapy as part of their physician's multiple sclerosis treatment plan. The patients must remain on a form of anti-CD20 therapy for the entirety of their enrollment in the study.
- Patients enrolled will be screened for at least one MS lesion with a 10mm diameter in one plane.
Exclusion criteria
- Treatment with corticosteroids within 30 days prior to screening.
- Patients unwilling or unable to undergo MR imaging, including patients with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- Poorly controlled hypertension, defined as either systolic \>160 or diastolic \>110. The addition of anti-hypertensives to control blood pressure is allowed for eligibility determination.
- Congestive Heart Failure ≥ NYHA Class II.
- History of clinically significant EKG abnormalities, including QT prolongation or a family history of prolonged QT syndrome.
- Myocardial infarction within 6 months of study entry.
- Individuals who are pregnant. Individuals of childbearing potential (defined below) must agree to undergo a urine pregnancy test prior to participating in the study scans. Pregnant individuals are excluded because there is an unknown but potential risk for adverse effects in the unborn child secondary to administration of HP 13C pyruvate to the study participant. A female is considered to not be of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), if they meet either of the following two criteria: (1) has reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy for removal of uterus and/or ovaries).
- Individuals who are breastfeeding/chestfeeding. Breastfeeding/chestfeeding individuals are excluded because there is an unknown but potential risk for adverse effects in the unborn/nursing child secondary to administration of HP 13C pyruvate to the study participant. Breastfeeding/chestfeeding should be discontinued before administration of HP 13C pyruvate.
- Known hypersensitivity to HP 13C pyruvate or any of its excipients.
- History of cancer within five years of enrollment date and/or history of chemotherapy within two years of enrollment date.
- Any dental braces or permanent or undetachable metals in the jaw or face.
- Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases that in the PI's judgment may affect the interpretation of study results or patient safety.
- Individuals with any condition or social circumstance that, in the opinion of the investigator, would impair the participant's ability to comply with study procedures.
- Glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m² on baseline visit or subsequent study visits, history of kidney disease or history of hypersensitivity to gadolinium contrast agent.
- Baseline EDSS \>6.5
Where
- San Francisco, California
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 8, 2026 · Source of record for eligibility and locations