Hyperpolarized Carbon Metabolic Imaging in Multiple Sclerosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAri Green
About 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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
HP 13C pyruvate injection
DrugEach 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.
MRI Scanner
DeviceMRI Brain scan
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: HP13C MRIOther 2 interventions
Trial outcomes
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.
Time frame
From study initiation to up to 15 months after enrollment of last subject.Secondary 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 3-months and one year following treatment initiation.
Percent changes in lesion HP 13C pyruvate metabolism measures. The following metabolism measures will be assessed at baseline and at 3-months and one year 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
Time frame
From study initiation to up to 15 months after enrollment of last subject.2
To determine the repeatability of HP 13C pyruvate metabolism measures in the MS lesions in patients with same-day repeated dose.
Repeatability of HP 13C pyruvate metabolism measures in the MS lesions The following metabolism measures will be assessed as repeat measures: * 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
Time frame
From study initiation to 15 months after enrollment of last subject.3
To determine the repeatability of HP 13C pyruvate metabolism measures in the MS lesions in patients with same-day repeated dose.
Repeatability of HP 13C pyruvate metabolism measures in the MS lesions The following metabolism measures will be assessed as repeat measures: * Peak HP 13C lactate/pyruvate and bicarbonate/pyruvate ratio * HP 13C lactate/pyruvate and bicarbonate/pyruvate AUC ratio * Metabolic rate constants kPL and kPB in inverse seconds
Time frame
From study initiation to 15 months after enrollment of last subject.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Ari Green
Lead sponsor
University of California, San Francisco
Sponsor institution
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
Source ClinicalTrials.gov