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

Glioma, Mixed Clinical Trial

— ERGO3  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04461938
• Other study ID #: ERGO3
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 19, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2023
• Source: Goethe University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Glioma
• Glioma, Mixed

Intervention

Other:
• Fasting
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.

Locations

Country	Name	City	State
Germany	Goethe University/Dr. Senckenbergischen Instituts für Neuroonkologie	Frankfurt	Hessen

Sponsors (1)

Lead Sponsor	Collaborator
Goethe University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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