Metabolic Characteristics of Brain Tumors Using Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopic Imaging (MRSI) (HPCIM)

Investigating Metabolic Characteristics of Intracranial Malignancy In Vivo Using Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopic Imaging (MRSI)

This is a non-randomized, purely observational, feasibility study to detect metabolic changes in patients with brain malignancy using a novel hyperpolarized [1-13C]pyruvate MRSI.

Study Overview

• Status: Recruiting
• Conditions: Brain Tumor Adult
• Intervention / Treatment: Drug: Hyperpolarized 13C-Pyruvate; Drug: Gadolinium

Detailed Description

The aim of this pilot study is to test the hypothesis that patients with brain malignancy present altered [1-13C]lactate and 13C-bicarbonate production from infused hyperpolarized [1-13C]pyruvate in tumor as compared to in normal-appearing brain regions. To achieve this aim investigators will assess metabolic phenotype in cancer patients with brain tumors (n = 20). Total target enrollment will be set at 25 subjects to account for attrition and screening failures.

During each imaging session, following localization of the tumor in brain, tissue characteristics and morphological changes will be evaluated with 1H MRI. Then, cerebral metabolism will be assessed utilizing 13C MRSI after an intravenous injection with hyperpolarized [1-13C]pyruvate. Finally, contrast-enhanced 1H MRI will be acquired. The study agent, hyperpolarized [1-13C]pyruvate, will be administered under a Food and Drug Administration (FDA) Investigational New Drug (IND), which was approved on 1/3/2017 (IND# 133229).

Preliminary data in human are essential to secure larger scale funding required for clinical studies. The investigators believe the ability to measure such metabolic shifts in vivo could have major significance in assessing the efficacy of multiple anti-tumor therapies currently under development that target reversing the Warburg effect as a means of controlling tumor growth. Brain tumor applications at the Advanced Imaging Research Center, Harold C. Simmons Comprehensive Cancer Center and the Neuro-Oncology Program of the Development of Neurological Surgery at the UT Southwestern Medical Center offer today a unique opportunity to lead globally the translational scientific efforts in this field.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Jeannie D Baxter, RN; Phone Number: 214-645-2726; Email: jeannie.baxter@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Jae Mo Park, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

20 Brain Tumor Patients

Description

Inclusion Criteria:

• Definitive diagnosis of brain tumors by imaging which demonstrates all kinds of brain malignancy, including glioma, meningioma, and brain metastases prior to any chemotherapy or radiation treatment.
• 18-70 years of age
• Ability to understand and the willingness to sign a written informed consent.
• All races and ethnicities will be included; subjects must be able to read and speak the English language. Once the protocol is established, Spanish-speaking participants will be included.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

Exclusion Criteria:

• Subjects who are receiving any other investigational agents.
• Previous or current treatment by radiation or chemotherapy.
• Concurrent illness including, but not limited to, ongoing or active infection, uncontrolled chronic diseases such as hypertension, lung disease, liver disease, kidney disease, diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects who have a history of alcohol abuse or illicit drug use.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• Subjects who have contraindication to contrast enhanced MRI examination

Contraindications to MRI examination include:

• Medically unstable

  • Heart failure
  • Severe LVOT outflow obstruction
  • Unstable angina
  • Child bearing
  • Lactating

• Any contraindication per MRI Screening Form including

  • Implants contraindicated at 3T, pacemakers
  • Implantable Cardioverter Defibrillator (ICD)
  • Claustrophobia

• Since each subject may be receiving a gadolinium-based contrast agent intravenously:

  • eGFR ≤ 30 mL/min/1.73m2
  • Sickle cell disease
  • Hemolytic anemia

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Brain Tumor Patients; Brain Tumor patients will receive a bolus of Hyperpolarized 13C-pyruvate during MRSI.	Drug: Hyperpolarized 13C-Pyruvate; Hyperpolarized 13C-pyruvate IV bolus followed by brain MRSI.; Other Names: HP [1-13C]pyruvate; Drug: Gadolinium; Brain MRI performed with and without gadolinium-based contrast.; Other Names: Gadavist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
13C-pyruvate Metabolic Product Ratio	Measurement of the ratio of metabolic products, [1-13C]lactate and 13C-bicarbonate, from hyperpolarized [1-13C]pyruvate will be used as an index of metabolic balance between glycolytic pathway and mitochondrial oxidative phosphorylation.	Screening (Baseline) and 1 day of Study Visit

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Jae Mo Park, PhD, UT Southwestern

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 23, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: STU 012017-070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No