Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Immunological changes
研究概览
简要总结
Nutritional interventions such as ketogenic diet (KD) or fasting are currently under evaluation as anti-cancer treatment. In glioma patient cohorts, the feasibility and safety of fasting in addition to antitumor treatment has been shown. However, it is still unclear whether fasting exerts effects on the glioma tumor tissue at all, and whether fasting causes metabolic or immunological changes in the glioma microenvironment that could be exploited therapeutically. Therefore, the central contribution of this study is to characterize metabolic and immunological changes in the glioma tumor tissue induced by a fasting cycle of 72 hours prior to biopsy or resection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •suspicion of glioma World Health Organization (WHO) grade II, III or IV as assessed by cerebral imaging (MRI)
- •MRI-suspected relapse of previously diagnosed glioma
- •interdisciplinary recommendation for resection or biopsy
- •karnofsky performance status >= 60, Eastern Cooperative Oncology Group Performance Status (ECOG) <= 2
- •creatinine <= 2,0 mg/dl, urea <= 100 mg/dl
- •alanine aminotransferase (ALAT), alanine aminotransferase aspartate transaminase (ASAT) <= 7x upper normal limit
- •international normalized ratio (INR) ≤ 1,5, thrombocytes > 100000/µl, leukocytes > 3000/µl
排除标准
- •bowel obstruction, subileus
- •insulin-dependent diabetes
- •dexamethasone >4mg/day
- •decompensated heart failure (NYHA > 2)
- •myocardial infarction within the last 6 months, symptomatic atrial fibrillation
- •severe acute infection or clinically relevant immunosuppression (HIV infection, granulocytopenia <1000/ µl, lymphocytopenia <500/ µl
- •malnutrition, cachexia (BMI <18)
- •other medical conditions that might increase the risk of the dietary intervention
- •pregnancy
- •uncontrolled thyroid function
- •pancreatic insufficiency
- •dementia or other clinically relevant alterations of the mental status which could impair the ability of the patient to apply to the diet or understand the informed consent of the study
- •major contraindications to MRI scanning (e.g. presence of implanted MRI-incompatible cardiac devices)
结局指标
主要结局
Immunological changes
时间窗: 5 days
Flow cytometry including T- and B-lymphocytes natural killer (NK) cells in blood samples. Analysis of gut microbiome prior to and following fasting.
General metabolic changes
时间窗: 5 days
Main target parameters of MR spectroscopic imaging are detection of intracerebral ketone bodies (acetone, acetoacetate, beta-hydroxybutyrate), changes in lactate and adenosine triphosphate / adenosine diphosphate (ATP/ADP) concentrations and changes in intracellular pH (pHi) as determined from the chemical shift difference between inorganic phosphate (Pi) and phosphocreatine (PCr). Tumor tissue and healthy appearing normal white matter of the contralateral hemisphere will be examined. Tumor tissue will be analysed by metabolome and proteome analysis and RNA sequencing. Patient serum will be analysed by proteome analysis.
Alterations in electric brain activity
时间窗: 5 days
Non-invasive electroencephalography (EEG) will be performed prior to and following fasting. It will be assessed with regard to chief frequencies and the presence of epilepsy-associated manifestations (e.g. epileptiform discharges, seizures).
Changes in metabolism - induction of ketosis
时间窗: 5 days
The presence of ketone bodies in patient blood will be assessed by capillary sampling from a finger or an ear lobe. The presence of ketone bodies in urine will be assessed by urine test strips.
次要结局
- Assessment to measure the tolerability of the diet by questionnaire(5 days)
- Intake of fluids and calories reported by dietary diary(5 days)
研究者
Michael Ronellenfitsch
Princial Investigator
Goethe University