GliomaPhase 2NCT03952598
Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy
A Phase 2 study testing HP 13C Pyruvate and 3T MRI scanner in people with Glioma and Gliomas, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Glioma, Gliomas, High Grade Glioma
- What is being tested?
- HP 13C Pyruvate and 3T MRI scanner
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Oct 2019to 28 Oct 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have histologically confirmed diffuse glioma with documented IDH1 or IDH2 mutation, confirmed by DNA sequencing the exception will be participants with brain lesions that are not safe for biopsy but clinically suspected to be diffuse glioma are allowed to enroll to the study to receive imaging study as part of the exploratory study
- 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
Show all 13Show fewer
- 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.
Who cannot join
- Participants who have contraindication to MRI examination, including, but not limited to, unable to receive gadolinium, medical instability, or any contraindication on MR Screening Form. Pregnant individuals are excluded because MRI contrast, planned to be used on this study, may be dangerous for the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to using of MRI contrast, breastfeeding should be discontinued for 72 hours following study imaging.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Studying the Biology of Higher-Grade Transformation in IDH-mutant Gliomas Via Longitudinal Observation of Tumor Metabolic Reprogramming Using Non-invasive Metabolic Imaging
Background:
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.
Read more
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.
Read the detailed description
Background:
- 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
- Glioma, Gliomas, High Grade Glioma, Malignant Glioma, Low Grade Glioma
- Being tested
- HP 13C Pyruvate, 3T MRI scanner
- Keywords
- Imaging, Higher-Grade Transformation, Biomarker for Cancer, High Grade Gliomas
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HP 13C PyruvateDrug
Contrast agent used with magnetic resonance spectroscopic imaging (MRSI)
3T MRI scannerDevice
Research proton MRS (1H-MRS) followed by DW-MRI
| Study group | Role | What they receive |
|---|---|---|
| 1/Arm 1 | Experimental | Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) -- THIS ARM IS NOW CLOSED Receives: Device: 3T MRI scanner |
| 2/Arm 2 | Experimental | Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) and HP 13C pyruvate MRSI Receives: Device: 3T MRI scanner |
| 3/Arms 3 | Experimental | Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) Receives: Drug: HP 13C Pyruvate; Device: 3T MRI scanner |
What is being measured
The primary outcome is the main question the study is designed to answer.
To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS)
Changes in the level of 2-HG correlate with the occurrence of higher-grade transformation (HT) and/or development of hypermutator phenotype (HMP) in patients with IDH-mutant gliomas
Measured: 5 years
Secondary outcomes (1)
Determine the utility of 2-HG detection by 1H-MRS to predict higher-grade transformation (HT) and hypermutator phenotype (HMP) by correlating the 2-HG level with pathological diagnosis and tumor mutational load of the tumor tissue at time of rec...
Usefulness of 2-HG detection and its correlation with high grade transformation and HMP
Measured: at clinical disease recurrence
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start16 Oct 2019
- Primary completion28 Oct 2026
- Study completion28 Oct 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jing Wu, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03952598
- Sponsor's protocol ID
- 190096
- Other IDs
- 19-C-0096
- Status last verified
- 4 Nov 2026
- First submitted
- 15 May 2019
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: BTRIS: All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@dbGaP: All large scale genomic sequencing data will be shared with subscribers to dbGaP.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studying the Biology of Higher-Grade Transformation in IDH-mutant Gliomas Via Longitudinal Observation of Tumor Metabolic Reprogramming Using Non-invasive Metabolic Imaging
- ClinicalTrials.gov ID
- NCT03952598
- Acronym / sponsor ID
- 190096
- Conditions
- Glioma, Gliomas, High Grade Glioma, Malignant Glioma, Low Grade Glioma
- Keywords
- Imaging, Higher-Grade Transformation, Biomarker for Cancer, High Grade Gliomas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 16 Oct 2019 (actual)
- Primary completion
- 28 Oct 2026 (actual)
- Study completion
- 28 Oct 2026 (actual)
- First posted
- 16 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
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
Background:
- 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1/Arm 1 | Experimental | Device: 3T MRI scannerMonitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) -- THIS ARM IS NOW CLOSED |
| 2/Arm 2 | Experimental | Device: 3T MRI scannerMonitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) and HP 13C pyruvate MRSI |
| 3/Arms 3 | Experimental | Drug: HP 13C Pyruvate, Device: 3T MRI scannerMonitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participants must have histologically confirmed diffuse glioma with documented IDH1 or IDH2 mutation, confirmed by DNA sequencing the exception will be participants with brain lesions that are not safe for biopsy but clinically suspected to be diffuse glioma are allowed to enroll to the study to receive imaging study as part of the exploratory study
- 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:
Key exclusion criteria (6 listed)
- Participants who have contraindication to MRI examination, including, but not limited to, unable to receive gadolinium, medical instability, or any contraindication on MR Screening Form. Pregnant individuals are excluded because MRI contrast, planned to be used on this study, may be dangerous for the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to using of MRI contrast, breastfeeding should be discontinued for 72 hours following study imaging.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HP 13C PyruvateContrast agent used with magnetic resonance spectroscopic imaging (MRSI) | Drug | 3/Arms 3 |
| 3T MRI scannerResearch proton MRS (1H-MRS) followed by DW-MRI | Device | 1/Arm 1, 2/Arm 2, 3/Arms 3 |
Primary outcome
To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS)
Time frame: 5 years
Changes in the level of 2-HG correlate with the occurrence of higher-grade transformation (HT) and/or development of hypermutator phenotype (HMP) in patients with IDH-mutant gliomas
1 secondary outcome
Determine the utility of 2-HG detection by 1H-MRS to predict higher-grade transformation (HT) and hypermutator phenotype (HMP) by correlating the 2-HG level with pathological diagnosis and tumor mutational load of the tumor tissue at time of rec...
Time frame: at clinical disease recurrence
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. BTRIS: All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@dbGaP: All large scale genomic sequencing data will be shared with subscribers to dbGaP.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jing Wu, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HP 13C Pyruvate and 3T MRI scanner in people with Glioma and Gliomas, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.