Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)

Study Overview
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Brief Summary
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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.

Official Title
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Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)

Conditions
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Glioma, Mixed

Intervention / Treatment
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* Other: Fasting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Fasting<br>All study participants follow the same dietary intervention; thus, no randomization will take place. | Other: Fasting<br>* The study intervention consists of one fasting cycle of 72 hours prior to biopsy/resection. Depending on clinical condition, patients can be hospitalized during the course of the study (e.g. need for medical assistance due to immobilization). Patients in good clinical condition will be admitted on day 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in metabolism - induction of ketosis | 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. | 5 days | 
| General metabolic changes | 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. | 5 days | 
| Immunological changes | Flow cytometry including T- and B-lymphocytes natural killer (NK) cells in blood samples. Analysis of gut microbiome prior to and following fasting. | 5 days | 
| Alterations in electric brain activity | 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). | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intake of fluids and calories reported by dietary diary | Patients will be asked keep a dietary diary for days 0 to 4 reporting on their intake of fluids and/or calories. | 5 days | 
| Assessment to measure the tolerability of the diet by questionnaire | A short questionnaire of 8 aspects concerning the tolerability of the diet will be handed out. The patients will be asked to grade their consensus to each statement by 1 to 5 where 1 is defined as not at all and 5 as very relevant for daily life. | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolism-nutritional intervention-ketogenic diet-fasting