Hyperpolarized Carbon Metabolic Imaging in Multiple Sclerosis

NCT07510607 | Recruiting Phase 2 FDA Drug FDA Device

• 2 other identifiers: 25-44242R01NS102156
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Hyperpolarized Carbon; Multiple Sclerosis; Anti-CD20; Ocrevus; RRMS; MS; Metabolic Imaging; Hyperpolarized Pyruvate; MRI; Magnetic Resonance Imaging; UCSF; Ari Green; Relapsing Remitting MS; ocrelizumab; Jeremy Gordon; MS biomarker; MS prognosis

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  From study initiation to up to 15 months after enrollment of last subject.

Secondary Outcomes (3)

• 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.

Study Arms (1)

HP13C MRI

OTHER

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.

Drug: HP 13C pyruvate injection; Device: MRI Scanner

Interventions

HP 13C pyruvate injection DRUG

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.

HP13C MRI

MRI Scanner DEVICE

MRI Brain scan

HP13C MRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ari Green: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Byers Hall

San Francisco, California, 94158, United States

RECRUITING

Related Publications (6)

• Ohl K, Tenbrock K, Kipp M. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp Neurol. 2016 Mar;277:58-67. doi: 10.1016/j.expneurol.2015.11.010. Epub 2015 Nov 26.

  PMID: 26626971 BACKGROUND

• Golman K, in 't Zandt R, Thaning M. Real-time metabolic imaging. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11270-5. doi: 10.1073/pnas.0601319103. Epub 2006 Jul 12.

  PMID: 16837573 BACKGROUND

• Nelson SJ, Kurhanewicz J, Vigneron DB, Larson PE, Harzstark AL, Ferrone M, van Criekinge M, Chang JW, Bok R, Park I, Reed G, Carvajal L, Small EJ, Munster P, Weinberg VK, Ardenkjaer-Larsen JH, Chen AP, Hurd RE, Odegardstuen LI, Robb FJ, Tropp J, Murray JA. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate. Sci Transl Med. 2013 Aug 14;5(198):198ra108. doi: 10.1126/scitranslmed.3006070.

  PMID: 23946197 BACKGROUND

• Tang S, Meng MV, Slater JB, Gordon JW, Vigneron DB, Stohr BA, Larson PEZ, Wang ZJ. Metabolic imaging with hyperpolarized 13 C pyruvate magnetic resonance imaging in patients with renal tumors-Initial experience. Cancer. 2021 Aug 1;127(15):2693-2704. doi: 10.1002/cncr.33554. Epub 2021 Apr 12.

  PMID: 33844280 BACKGROUND

• Park I, Larson PEZ, Gordon JW, Carvajal L, Chen HY, Bok R, Van Criekinge M, Ferrone M, Slater JB, Xu D, Kurhanewicz J, Vigneron DB, Chang S, Nelson SJ. Development of methods and feasibility of using hyperpolarized carbon-13 imaging data for evaluating brain metabolism in patient studies. Magn Reson Med. 2018 Sep;80(3):864-873. doi: 10.1002/mrm.27077. Epub 2018 Jan 10.

  PMID: 29322616 BACKGROUND

• Gordon JW, Chen HY, Nickles T, Lee PM, Bok R, Ohliger MA, Okamoto K, Ko AH, Larson PEZ, Wang ZJ. Hyperpolarized 13C Metabolic MRI of Patients with Pancreatic Ductal Adenocarcinoma. J Magn Reson Imaging. 2024 Aug;60(2):741-749. doi: 10.1002/jmri.29162. Epub 2023 Dec 2.

  PMID: 38041836 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Ari Green, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology, Chief of the Division of Neuroimmunology and Glial Biology

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 3, 2026
• Study Start: June 3, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 9-36 months following publication.
• Access Criteria: Proposals should be directed to the Principal Investigator; to gain access, data requestors will need to sign a data access agreement.

Locations

US (1)