Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3) (ERGO3)
Primary Purpose
Glioma, Mixed
Status
Active
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Fasting
Sponsored by
About this trial
This is an interventional basic science trial for Glioma, Mixed focused on measuring metabolism-nutritional intervention-ketogenic diet-fasting
Eligibility Criteria
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)
Sites / Locations
- Goethe University/Dr. Senckenbergischen Instituts für Neuroonkologie
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Fasting
Arm Description
All study participants follow the same dietary intervention; thus, no randomization will take place.
Outcomes
Primary Outcome Measures
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.
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.
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.
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).
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04461938
Brief Title
Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)
Acronym
ERGO3
Official Title
Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 19, 2020 (Actual)
Primary Completion Date
December 31, 2022 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Goethe University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma, Mixed
Keywords
metabolism-nutritional intervention-ketogenic diet-fasting
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fasting
Arm Type
Other
Arm Description
All study participants follow the same dietary intervention; thus, no randomization will take place.
Intervention Type
Other
Intervention Name(s)
Fasting
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in metabolism - induction of ketosis
Description
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.
Time Frame
5 days
Title
General metabolic changes
Description
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.
Time Frame
5 days
Title
Immunological changes
Description
Flow cytometry including T- and B-lymphocytes natural killer (NK) cells in blood samples.
Analysis of gut microbiome prior to and following fasting.
Time Frame
5 days
Title
Alterations in electric brain activity
Description
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).
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Intake of fluids and calories reported by dietary diary
Description
Patients will be asked keep a dietary diary for days 0 to 4 reporting on their intake of fluids and/or calories.
Time Frame
5 days
Title
Assessment to measure the tolerability of the diet by questionnaire
Description
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.
Time Frame
5 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael W Ronellenfitsch, PD
Organizational Affiliation
Goethe University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Goethe University/Dr. Senckenbergischen Instituts für Neuroonkologie
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
12. IPD Sharing Statement
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Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)
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