Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy
NCT ID: NCT03952598
Last Updated: 2025-12-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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SUSPENDED
PHASE2
42 participants
INTERVENTIONAL
2019-10-16
2025-12-31
Brief Summary
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Glioma is a type of brain cancer. Some of these tumors have gene mutations. These mutations can cause a substance called 2-HG to build up in the brain. This makes the tumors more aggressive. Researchers want to better understand 2-HG buildup in the brain. They hope this can help them design better ways to test for gliomas.
Objective:
To monitor the level of 2-HG in the brains of people with gliomas that have mutations in the IDH1 or IDH2 genes.
Eligibility:
People ages 18 and older with gliomas with mutations in the IDH1 or IDH2 genes
Design:
Participants will be screened with:
Medical and cancer history
Physical exam
Reviews of their symptoms and ability to perform normal activities
Blood and urine tests
MRI scan
Samples of their tumor from a past surgery
Documentation of their diagnosis and mutation status
Participants will have an initial evaluation. This will include repeats of screening tests. It will also include:
Neurological exam
MRS and MRI scans of the brain: Participants will lie on a table that slides into a metal cylinder. A coil or soft padding will be placed around their head. They will have a contrast agent injected into a vein. Pictures will be taken of the brain.
Participants will have follow-up visits every 2-6 month for the rest of their life. Visits will include scans.
...
Detailed Description
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* Glioma is the most common malignant brain tumor. Genes coding for isocitrate dehydrogenase (IDH), a metabolic enzyme, are frequently mutated in gliomas, particularly lower-grade gliomas (LGGs). IDH mutation causes a unique tumor biology, including the accumulation of 2-hydroxyglutarate (2-HG), an oncometabolite, which in turn causes genomic hypermethylation and tumorigenesis.
* Despite having a better prognosis compared to their IDH WT counterparts, IDH-mutant LGGs undergo a slow but unremitting higher-grade transformation (HT) and eventually become high grade gliomas (HGGs). A subset of patients with transformed HGGs develop a hypermutator phenotype (HMP), possibly related to previous treatment with alkylating agents. The timeline for the development of HT and HMP is unpredictable and there is no known way to prevent them from happening, largely due to a lack of understanding their biological mechanisms and lack of a non-invasive approach for potential early detection.
* Metabolic imaging, including proton magnetic resonance spectroscopy (MRS) and hyperpolarized (HP) 13C-Pyruvate MRSI, can safely detect the in vivo metabolic changes in humans.
* This clinical study will allow a longitudinal monitoring of participants with IDH-mutant gliomas for detection of disease progression, which is associated with metabolic alterations, provide an unprecedented opportunity for biopsy of the tumor for diagnostic confirmation and interrogation of the mechanisms of HT and HMP, and potentially providing a specific treatment approach for HMP which has been refractory to conventional brain tumor treatments.
Objective:
To detect and monitor the quantitative levels of 2-HG and lactate/pyruvate ratio longitudinally in participants with IDH-mutant gliomas via proton MRS and HP 13C pyruvate MRSI, respectively
Eligibility:
* Participant has glioma harboring IDH1 or IDH2 mutation confirmed by DNA sequencing.
* Age \>=18 years, KPS \>= 70%
Design:
* This is a prospective observational study. We will recruit up to 270 eligible participants in the next 5 years.
* The relationship between the occurrence of HT and the changes in 2-HG level and the ratio of lactate/pyruvate will be evaluated using the proportional hazard model with the latter as the time-dependent covariates.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
DIAGNOSTIC
NONE
Study Groups
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1/Arm 1
Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) -- THIS ARM IS NOW CLOSED
3T MRI scanner
Research proton MRS (1H-MRS) followed by DW-MRI
2/Arm 2
Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) and HP 13C pyruvate MRSI
3T MRI scanner
Research proton MRS (1H-MRS) followed by DW-MRI
3/Arms 3
Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS)
HP 13C Pyruvate
Contrast agent used with magnetic resonance spectroscopic imaging (MRSI)
3T MRI scanner
Research proton MRS (1H-MRS) followed by DW-MRI
Interventions
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HP 13C Pyruvate
Contrast agent used with magnetic resonance spectroscopic imaging (MRSI)
3T MRI scanner
Research proton MRS (1H-MRS) followed by DW-MRI
Eligibility Criteria
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Inclusion Criteria
* Participants must have measurable disease.
* Age \>=18 years. Tumor biology of IDH-mutant gliomas are different in pediatric tumors. Therefore, children will be excluded from the study.
* Karnofsky performance \>= 70%.
* Participants must have documented normal kidney function as defined below:
Creatinine within normal institutional limits
OR
Creatinine clearance \>60 mL/min/1.73 m2 for Participants with creatinine levels above institutional normal (Measured or calculated creatinine clearance
-Participants must have adequate liver function as defined below:
total bilirubin \<=2x ULN (ULN 1.3 mg/dl) except for participants with Gilbert Syndrome
AST \< 3x ULN (ULN 34U/L)
ALT \< 3x ULN (ULN 55U/L)
-Ability of participants to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of this study, and that this is not a therapeutic clinical trial.
Exclusion Criteria
* Participants weighing \> 350 lbs. (weight limit for scanner table), or unable to fit within the imaging gantry
* Poorly controlled hypertension, with blood pressure \>150/90 mmHg.
* Congestive heart failure with New York Heart Association (NYHA) status \> 2.
* A medical history of clinically significant EKG abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction (MI) less than 1 year ago with ensuing unstable EKG.
* Ongoing acute or chronic pulmonary bronchospastic disease, including a history of chronic obstructive pulmonary disease or asthma with an exacerbation within the past year.
18 Years
120 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Jing Wu, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)
Locations
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National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Countries
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Related Links
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NIH Clinical Center Detailed Web Page
Other Identifiers
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19-C-0096
Identifier Type: -
Identifier Source: secondary_id
190096
Identifier Type: -
Identifier Source: org_study_id