이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

MR 분광법을 사용하여 2-하이드록시글루타레이트(2-HG)의 세로 관찰을 통해 IDH 돌연변이 신경교종의 생물학 연구

2026년 11월 5일 업데이트: National Cancer Institute (NCI)

MR 분광법을 사용하여 2-Hydroxyglutarate(2-HG)의 세로 관찰을 통해 IDH 돌연변이 신경교종의 생물학 연구

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.

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (실제)

42

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 미국
    • Maryland
      • Bethesda, Maryland, 미국, 20892
        • National Institutes of Health Clinical Center

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

  • INCLUSION CRITERIA:
  • 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

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 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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 특수 증상
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 1/Arm 1

Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) -- THIS ARM IS NOW CLOSED
장치: 3T MRI scanner

Research proton MRS (1H-MRS) followed by DW-MRI
실험적: 2/Arm 2

Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS) and HP 13C pyruvate MRSI
장치: 3T MRI scanner

Research proton MRS (1H-MRS) followed by DW-MRI
실험적: 3/Arms 3

Monitoring of quantitative levels of 2-hydroxyglutarate (2-HG) via proton magnetic resonance spectroscopy (1H-MRS)
장치: 3T MRI scanner

Research proton MRS (1H-MRS) followed by DW-MRI

의약품: HP 13C Pyruvate

Contrast agent used with magnetic resonance spectroscopic imaging (MRSI)

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
To monitor the quantitative levels of 2-hydroxyglutarate (2-HG) longitudinally in patients with IDH mutant gliomas via proton magnetic resonance spectroscopy (1H-MRS)
기간: 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
5 years

2차 결과 측정

결과 측정
측정값 설명
기간
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...
기간: at clinical disease recurrence

Usefulness of 2-HG detection and its correlation with high grade transformation and HMP
at clinical disease recurrence

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Cancer Institute (NCI)

수사관

  • 수석 연구원: Jing Wu, M.D., National Cancer Institute (NCI)

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

유용한 링크

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2019년 10월 16일

기본 완료 (실제)

2026년 10월 28일

연구 완료 (실제)

2026년 10월 28일

연구 등록 날짜

최초 제출

2019년 5월 15일

QC 기준을 충족하는 최초 제출

2019년 5월 15일

처음 게시됨 (실제)

2019년 5월 16일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 11월 6일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 11월 5일

마지막으로 확인됨

2026년 11월 4일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 190096
  • 19-C-0096

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

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.

IPD 공유 기간

BTRIS: Clinical data available during the study and indefinitely.@@@@@@dbGaP: Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.

IPD 공유 액세스 기준

BTRIS: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@dbGaP: Genomic data are made available via dbGaP through requests to the data custodians.

IPD 공유 지원 정보 유형

  • 연구_프로토콜
  • 수액
  • ICF

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다