Calorie-restricted, Ketogenic Diet and Transient Fasting During Reirradiation for Patients With Recurrent Glioblastoma (ERGO2)

Calorie-restricted, Ketogenic Diet and Transient Fasting vs. Standard Nutrition During Reirradiation for Patients With Recurrent Glioblastoma: the ERGO2 Study

Increased glucose metabolism is characteristic for solid tumors. Thereby, glucose is important for the generation of ATP, supply of anabolic substrates and defense against reactive oxygen species in tumor cells. In preclinical models, restricting glucose availability using a ketogenic diet, calorie-restriction or transient fasting inhibits tumor growth.

Therefore, the purpose of the study is to evaluate whether a calorie-restricted, ketogenic diet and transient fasting can enhance the efficacy of reirradiation in patients with recurrent glioblastoma.

Study Overview

• Status: Completed
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Dietary supplement: calorie-restricted ketogenic diet and transient fasting; Dietary supplement: standard nutrition

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Frankfurt, Germany
    • Dr. Senckenberg Institute of Neurooncology
  • Tuebingen, Germany
    • University of Tuebingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age >= 18 years
• recurrence of a histologically confirmed glioblastoma or gliosarcoma
• at least 6 months after first surgery
• at least 6 months after first radiotherapy
• interdisciplinary recommendation for reirradiation
• karnofsky performance status >= 60, ECOG <= 2
• creatinine <= 2,0 mg/dl, urea <= 100 mg/dl
• ALAT, ASAT <= 7x upper normal limit

Exclusion Criteria:

• bowel obstruction, subileus
• insulin-dependent diabetes
• decompensated heart failure (NYHA > 2)
• myocardial infarction within the last 6 months, symptomatic atrial fibrillation
• severe acute infection
• malnutrition, cachexia
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ketogenic diet and transient fasting; Calorie-restricted, ketogenic diet and transient fasting during reirradiation	Dietary supplement: calorie-restricted ketogenic diet and transient fasting; On day 1-3 and day 7-9, restriction of carbohydrates to < 60 g and of calories to 21-23 kcal/kg per day, on day 4-6 fasting. On day 1-3 and 7-9, restriction of carbohydrates can be supported by the use of drinks provided by "Tavarlin".
Active Comparator: standard nutrition; nutrition according to recommendations of the German society for nutrition during reirradiation	Dietary supplement: standard nutrition; nutrition as recommended by the german society for nutrition, 30 kcal/kg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free-survival	Progression-free-survival rates 6 months after reirradiation based on response assessment in neuro-oncology criteria (RANO)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Measured as Median Number of Days on Diet Per Patient and Average Calorie and Carbohydrate Intake Per Day During Day 1-9	Feasibility of the calorie-restricted, ketogenic diet and the transient fasting measured as median number of days on diet per patient and average calorie and carbohydrate intake per day during day 1-9	day 1-12
Safety and Tolerability as Defined as Number of Patients With Adverse Events	Safety and tolerability of the calorie-restricted, ketogenic diet and the transient fasting as defined as number of patients with adverse events	day 1-12
Progression-free-survival	progression-free-survival rates 1 month and 3 month after reirradiation	1 month, 3 months
Overall Survival	overall survival after the reirradiation	12 months
Frequency of Seizures	frequency of seizures at day 1-12	day 1-12
Ketosis	urine and blood ketosis and metabolic parameters (glucose, insulin, IGF-1) during day 1-12	day 1-12
Quality of Life as Measured by the EORTC Quality of Life Questionnaire	Quality of life at day 1-12 as measured by the EORTC Quality of Life Questionnaire	day 1-12
Depression	depression as measured by SCL-90 at day 1-12	day 1-12
Attention	attention as measured by d2-testing at day 1-12	day 1-12
Response	response assessment 1 month after reirradiation	1 month

Collaborators and Investigators

• Sponsor: Johann Wolfgang Goethe University Hospital
• Collaborators: TAVARLIN (Darmstadt, Germany)

Publications and helpful links

General Publications

• Allaf M, Elghazaly H, Mohamed OG, Fareen MFK, Zaman S, Salmasi AM, Tsilidis K, Dehghan A. Intermittent fasting for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2021 Jan 29;1(1):CD013496. doi: 10.1002/14651858.CD013496.pub2.
• Voss M, Wenger KJ, von Mettenheim N, Bojunga J, Vetter M, Diehl B, Franz K, Gerlach R, Ronellenfitsch MW, Harter PN, Hattingen E, Steinbach JP, Rodel C, Rieger J. Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial. Eur J Nutr. 2022 Feb;61(1):477-487. doi: 10.1007/s00394-021-02666-1. Epub 2021 Sep 6.
• Voss M, Wagner M, von Mettenheim N, Harter PN, Wenger KJ, Franz K, Bojunga J, Vetter M, Gerlach R, Glatzel M, Paulsen F, Hattingen E, Baehr O, Ronellenfitsch MW, Fokas E, Imhoff D, Steinbach JP, Rodel C, Rieger J. ERGO2: A Prospective, Randomized Trial of Calorie-Restricted Ketogenic Diet and Fasting in Addition to Reirradiation for Malignant Glioma. Int J Radiat Oncol Biol Phys. 2020 Nov 15;108(4):987-995. doi: 10.1016/j.ijrobp.2020.06.021. Epub 2020 Jun 30.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (Estimate): December 21, 2012

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 30, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: nutrition; glioma; ketogenic diet; fasting; reirradiation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: ERGO2