<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04461938</url>
  </required_header>
  <id_info>
    <org_study_id>ERGO3</org_study_id>
    <nct_id>NCT04461938</nct_id>
  </id_info>
  <brief_title>Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)</brief_title>
  <acronym>ERGO3</acronym>
  <official_title>Characterization of Metabolic Changes in the Glioma Tumor Tissue Induced by Transient Fasting (ERGO3)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Goethe University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Goethe University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Nutritional interventions such as ketogenic diet (KD) or fasting are currently under&#xD;
      evaluation as anti-cancer treatment. In glioma patient cohorts, the feasibility and safety of&#xD;
      fasting in addition to antitumor treatment has been shown. However, it is still unclear&#xD;
      whether fasting exerts effects on the glioma tumor tissue at all, and whether fasting causes&#xD;
      metabolic or immunological changes in the glioma microenvironment that could be exploited&#xD;
      therapeutically. Therefore, the central contribution of this study is to characterize&#xD;
      metabolic and immunological changes in the glioma tumor tissue induced by a fasting cycle of&#xD;
      72 hours prior to biopsy or resection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 19, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in metabolism - induction of ketosis</measure>
    <time_frame>5 days</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>General metabolic changes</measure>
    <time_frame>5 days</time_frame>
    <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.&#xD;
Tumor tissue will be analysed by metabolome and proteome analysis and RNA sequencing.&#xD;
Patient serum will be analysed by proteome analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunological changes</measure>
    <time_frame>5 days</time_frame>
    <description>Flow cytometry including T- and B-lymphocytes natural killer (NK) cells in blood samples.&#xD;
Analysis of gut microbiome prior to and following fasting.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Alterations in electric brain activity</measure>
    <time_frame>5 days</time_frame>
    <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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intake of fluids and calories reported by dietary diary</measure>
    <time_frame>5 days</time_frame>
    <description>Patients will be asked keep a dietary diary for days 0 to 4 reporting on their intake of fluids and/or calories.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment to measure the tolerability of the diet by questionnaire</measure>
    <time_frame>5 days</time_frame>
    <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 &quot;1&quot; is defined as &quot;not at all&quot; and 5 as &quot;very relevant&quot; for daily life.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Glioma, Mixed</condition>
  <arm_group>
    <arm_group_label>Fasting</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All study participants follow the same dietary intervention; thus, no randomization will take place.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fasting</intervention_name>
    <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.</description>
    <arm_group_label>Fasting</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  suspicion of glioma World Health Organization (WHO) grade II, III or IV as assessed by&#xD;
             cerebral imaging (MRI)&#xD;
&#xD;
          -  MRI-suspected relapse of previously diagnosed glioma&#xD;
&#xD;
          -  interdisciplinary recommendation for resection or biopsy&#xD;
&#xD;
          -  karnofsky performance status &gt;= 60, Eastern Cooperative Oncology Group Performance&#xD;
             Status (ECOG) &lt;= 2&#xD;
&#xD;
          -  creatinine &lt;= 2,0 mg/dl, urea &lt;= 100 mg/dl&#xD;
&#xD;
          -  alanine aminotransferase (ALAT), alanine aminotransferase aspartate transaminase&#xD;
             (ASAT) &lt;= 7x upper normal limit&#xD;
&#xD;
          -  international normalized ratio (INR) ≤ 1,5, thrombocytes &gt; 100000/µl, leukocytes &gt;&#xD;
             3000/µl&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  bowel obstruction, subileus&#xD;
&#xD;
          -  insulin-dependent diabetes&#xD;
&#xD;
          -  dexamethasone &gt;4mg/day&#xD;
&#xD;
          -  decompensated heart failure (NYHA &gt; 2)&#xD;
&#xD;
          -  myocardial infarction within the last 6 months, symptomatic atrial fibrillation&#xD;
&#xD;
          -  severe acute infection or clinically relevant immunosuppression (HIV infection,&#xD;
             granulocytopenia &lt;1000/ µl, lymphocytopenia &lt;500/ µl&#xD;
&#xD;
          -  malnutrition, cachexia (BMI &lt;18)&#xD;
&#xD;
          -  other medical conditions that might increase the risk of the dietary intervention&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  uncontrolled thyroid function&#xD;
&#xD;
          -  pancreatic insufficiency&#xD;
&#xD;
          -  dementia or other clinically relevant alterations of the mental status which could&#xD;
             impair the ability of the patient to apply to the diet or understand the informed&#xD;
             consent of the study&#xD;
&#xD;
          -  major contraindications to MRI scanning (e.g. presence of implanted MRI-incompatible&#xD;
             cardiac devices)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael W Ronellenfitsch, PD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Goethe University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Goethe University/Dr. Senckenbergischen Instituts für Neuroonkologie</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>March 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Goethe University</investigator_affiliation>
    <investigator_full_name>Michael Ronellenfitsch</investigator_full_name>
    <investigator_title>Princial Investigator</investigator_title>
  </responsible_party>
  <keyword>metabolism-nutritional intervention-ketogenic diet-fasting</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04461938
org study id: ERGO3
nct id: NCT04461938
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Changes in metabolism - induction of ketosis
time frame: 5 days
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.
measure: General metabolic changes
time frame: 5 days
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.
measure: Immunological changes
time frame: 5 days
description: Flow cytometry including T- and B-lymphocytes natural killer (NK) cells in blood samples.
Analysis of gut microbiome prior to and following fasting.
measure: Alterations in electric brain activity
time frame: 5 days
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).
measure: Intake of fluids and calories reported by dietary diary
time frame: 5 days
description: Patients will be asked keep a dietary diary for days 0 to 4 reporting on their intake of fluids and/or calories.
measure: Assessment to measure the tolerability of the diet by questionnaire
time frame: 5 days
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.
arm group label: Fasting
arm group type: Other
description: All study participants follow the same dietary intervention; thus, no randomization will take place.
intervention type: Other
intervention name: Fasting
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.
arm group label: Fasting
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael W Ronellenfitsch, PD
role: Principal Investigator
affiliation: Goethe University
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Goethe University
investigator full name: Michael Ronellenfitsch
investigator title: Princial Investigator
mesh term: Glioma