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

NCT04461938 | Active Not Recruiting

• 1 other identifier: ERGO3
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioma, Mixed

Keywords

metabolism-nutritional intervention-ketogenic diet-fasting

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Intake of fluids and calories reported by dietary diary

  5 days

• Assessment to measure the tolerability of the diet by questionnaire

  5 days

Study Arms (1)

Fasting

OTHER

All study participants follow the same dietary intervention; thus, no randomization will take place.

Other: Fasting

Interventions

Fasting OTHER

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.

Fasting

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Goethe University: lead

Study Sites (1)

Dr. Senckenberg Institute of Neurooncology, University Medicine Fankfurt, Goethe-University

Frankfurt am Main, Hesse, 60590, Germany

Location

Related Publications (1)

• Alcicek S, Dive I, Thomas DC, Prinz V, Forster MT, Czabanka M, Weber KJ, Steinbach JP, Ronellenfitsch MW, Hattingen E, Pilatus U, Wenger KJ. 2D 1H sLASER Long-TE and 3D 31P Chemical Shift Imaging at 3 T for Monitoring Fasting-Induced Changes in Brain Tumor Tissue. J Magn Reson Imaging. 2025 Jan;61(1):426-438. doi: 10.1002/jmri.29422. Epub 2024 May 9.

  PMID: 38722043 RESULT

MeSH Terms

Conditions

Glioma

Interventions

Angptl4 protein, mouse

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Michael W. Ronellenfitsch, Prof. Dr. Dr.

  Goethe University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Princial Investigator

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: July 8, 2020
• Study Start: August 19, 2020
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2025
• Last Updated: October 17, 2024

Record last verified: 2024-10

Locations

DE (1)