<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/NCT02999152</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0901</org_study_id>
    <secondary_id>2016-A01446-45</secondary_id>
    <nct_id>NCT02999152</nct_id>
  </id_info>
  <brief_title>Validation of Radio-induced Damage Biomarkers</brief_title>
  <acronym>BIOM-DRI</acronym>
  <official_title>Validation of Radio-induced Damage Biomarkers : BIOM-DRI Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Saint Etienne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut de Recherche Biomedicale des Armees</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut de Cancérologie de la Loire</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Saint Etienne</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>
      The aim of this study is to confirm in humans the relevance and the kinetics of radio-induced&#xD;
      bio-markers in plasma and urines, previously described at the preclinical stage.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The nuclear and radiologic risks monitoring is a major preoccupation for our society. During&#xD;
      an accident, it is primordial to define the biologic dosimetry. The dose and distribution&#xD;
      knowledge is crucial for the medical care. Indeed, Total Body Irradiation (TBI) and Partial&#xD;
      Body Irradiation (PBI) do not have the same clinical outcome. A Total Body Irradiation&#xD;
      induces an acute radiation syndrome with a Medullary Aplasia. A quick diagnostic would allow&#xD;
      the optimization of the medical care.&#xD;
&#xD;
      Nowadays, the analyse of the chromosome with two centromeres is the current norm to estimate&#xD;
      the radiation dose, but this technique is time consuming, and not adapted to an emergency&#xD;
      situation, and to a large population.&#xD;
&#xD;
      The new genetic techniques could permit the quick radiation dosimetry diagnosis. The research&#xD;
      of early exposition bio-markers seems to be of a major interest. These bio-markers would&#xD;
      allow to rapidly define the radiations perceived by an exposed subject, before the apparition&#xD;
      of the symptoms, and by the way, to conduct to a therapeutic strategy more adapted to the&#xD;
      patient.&#xD;
&#xD;
      In this purpose, the present study will need blood and urines samples of patients totally or&#xD;
      partially exposed to radiations, according to their usual medical care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low rythm of inclusions, financial support terminated&#xD;
  </why_stopped>
  <start_date type="Actual">June 22, 2017</start_date>
  <completion_date type="Actual">June 15, 2020</completion_date>
  <primary_completion_date type="Actual">June 15, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Level of haematological and biochemical markers</measure>
    <time_frame>Day 3</time_frame>
    <description>The following bio-markers levels will be calculated :&#xD;
Blood count,&#xD;
Pads,&#xD;
Haemoglobin,&#xD;
Serum iron,&#xD;
Plasma urea,&#xD;
Urinary urea&#xD;
Total protein,&#xD;
albumin&#xD;
creatin kinase,&#xD;
Aspartate Amino Transferase,&#xD;
alkaline phosphatase,&#xD;
Total cholesterol,&#xD;
Triglycerides,&#xD;
Plasma creatinine&#xD;
Creatinine clearance,&#xD;
Urinary creatinine&#xD;
Blood glucose,&#xD;
Citrulline,&#xD;
erythropoietin,&#xD;
Plasma amylase,&#xD;
Myoglobin,&#xD;
Troponin,&#xD;
C reactive protein,&#xD;
Rate of prothrombin,&#xD;
Fibrinogen,&#xD;
D-Dimer,&#xD;
Factor-V,&#xD;
Fms-like tyrosine kinase 3-Ligand.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantification of chromosomal aberrations</measure>
    <time_frame>Day 3</time_frame>
    <description>Quantification of chromosomal aberrations will be performed on the blood samples performed at days 0, 1, 2 and 3 after the beginning of the rays perform in the usual practice.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Detection of biochemical markers</measure>
    <time_frame>Day 3</time_frame>
    <description>The presence or absence of these markers will be notified:&#xD;
Interleukin 1&#xD;
Interleukin 6&#xD;
Interleukin 8&#xD;
Interleukin 18&#xD;
Tumor Necrosis Factor alpha (TNF-alpha)&#xD;
Brain-Derived Neurotrophic Factor (BDNF)&#xD;
Granulocyte Colony-Stimulating Factor (G - CSF)&#xD;
Serum amyloid A (SAA)&#xD;
Growth Arrest and DNA Damage-inducible 45 (GADD45)&#xD;
Intestinal-type Fatty Acid-Binding Protein (FABP-I)&#xD;
Liver-type Fatty Acid-Binding Protein (L-FABP)&#xD;
Heart-type Fatty Acid-Binding Protein (H-FABP)&#xD;
Stem Cell Factor Receptor CD117</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolomics markers levels</measure>
    <time_frame>Day 2</time_frame>
    <description>The metabolomic levels of the following molecules will be calculated on urine samples:&#xD;
3 - Sulfate Hydroxytyrosol&#xD;
1, 6-Anhydro-beta-D-glucose&#xD;
1 - Methylnicotinamide&#xD;
2 - Hydroxyisobutyrate&#xD;
3 - aminoisobutyrate&#xD;
3 - hydroxyisovalerate&#xD;
3 - Hydroxymandelate&#xD;
3 - Indoxylsulfate&#xD;
4 - Hydroxyphenylacetate&#xD;
Acetate&#xD;
Acetone&#xD;
Adipic acid&#xD;
Alanine&#xD;
Betaine&#xD;
Carnitine&#xD;
Choline&#xD;
Cis-Aconitate&#xD;
Citrate&#xD;
Creatine&#xD;
Creatinine&#xD;
dimethylamine&#xD;
Ethanolamine&#xD;
Formats&#xD;
Glucose&#xD;
Glycine&#xD;
Glycolate&#xD;
Hippurate&#xD;
Histidine&#xD;
Hypoxanthine&#xD;
Isethionic acid&#xD;
Lactate&#xD;
Methanol&#xD;
Methylamine&#xD;
N, N-Dimethylglycine&#xD;
N - Acetylserotonin sulfate&#xD;
N - Acetyltaurine&#xD;
O - Acetylcarnitine&#xD;
O - Phosphocholine&#xD;
Pi-methylhistidine&#xD;
Pyroglutamate&#xD;
Succinate&#xD;
Tartrate&#xD;
Tau-methylhistidine&#xD;
Taurine&#xD;
Threonine&#xD;
trans-Aconitate&#xD;
Trigonelline&#xD;
Trimethylamine N-oxide&#xD;
Tyramine sulfate&#xD;
Tyrosine&#xD;
Tyrosol sulfate&#xD;
Uracil&#xD;
Robert acid&#xD;
Valine&#xD;
Xanthine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total dose of radiation</measure>
    <time_frame>Day 3</time_frame>
    <description>The total dose of radiation will be calculated for each patient and compared will the biologic results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiation field</measure>
    <time_frame>Day 3</time_frame>
    <description>The radiation field will be define for each patient and compared with the biological results.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Bone Metastasis</condition>
  <condition>Malignant Hemopathy</condition>
  <arm_group>
    <arm_group_label>Total Body Irradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient suffering from a malignant blood disease that requires a total body radiation, without (or prior to) a concomitant chemotherapy, according to the following protocol: 2x2 Gray per day, for 3 days. Blood and urines samples will be performed at days 0, 1, 2 and 3 of the treatment plan.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Partial Body Irradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient with at least one bone metastasis localized at the pelvis and requiring partial body radiation therapy without associated chemotherapy, according to the following protocol: 4 Gray per day for 5 days will perform blood and urines samples at days 0, 1, 2 and 3 after the beginning of the radiation treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood and urines samples</intervention_name>
    <description>For all patients the blood samples must be organized: Before, 4 hours (+/-30 min), 1 day, 2 days, and 3 days after the start of the radiation therapy.&#xD;
Collections of urine must be organized: Before, 1 day, and 2 days after the radiation therapy.</description>
    <arm_group_label>Partial Body Irradiation</arm_group_label>
    <arm_group_label>Total Body Irradiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  More than 18 years old&#xD;
&#xD;
          -  For the group A:&#xD;
&#xD;
        Patient suffering from a malignant blood disease requiring a whole-body radiation, without&#xD;
        (or prior to) a concomitant chemotherapy, according to the following protocol: 2x2 Gray per&#xD;
        day, during 3 days.&#xD;
&#xD;
          -  OR For the group B:&#xD;
&#xD;
        Patient with one (or more) pelvis metastasis requiring radiation therapy without&#xD;
        concomitant chemotherapy, according to the following protocol: 4 Gray per day for 5 days.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  More than 70 years old,&#xD;
&#xD;
          -  Subject presenting abnormal blood count (grade 3),&#xD;
&#xD;
          -  Person with a not controlled chronic illness,&#xD;
&#xD;
          -  Subject presenting an abnormal hepatic assessment (grade 3),&#xD;
&#xD;
          -  Subject having already received ionizing treatments,&#xD;
&#xD;
          -  Subject reached HIV, hepatitis C or any other progressive infectious diseases,&#xD;
&#xD;
          -  Pregnant women or nursing mothers,&#xD;
&#xD;
          -  Person under protection of justice or unable to give consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicolas Magné, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut de Cancérologie Lucien Neuwirth</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut de Cancérologie Lucien Neuwirth</name>
      <address>
        <city>Saint-Priest en Jarez</city>
        <zip>42270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>February 4, 2022</last_update_submitted>
  <last_update_submitted_qc>February 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bio-markers</keyword>
  <keyword>Radiation</keyword>
  <keyword>Appropriate therapeutic strategy</keyword>
  <keyword>Total Body Irradiation</keyword>
  <keyword>Partial Body Irradiation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02999152
org study id: 2016-0901
secondary id: 2016-A01446-45
nct id: NCT02999152
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to confirm in humans the relevance and the kinetics of radio-induced
      bio-markers in plasma and urines, previously described at the preclinical stage.
The nuclear and radiologic risks monitoring is a major preoccupation for our society. During
      an accident, it is primordial to define the biologic dosimetry. The dose and distribution
      knowledge is crucial for the medical care. Indeed, Total Body Irradiation (TBI) and Partial
      Body Irradiation (PBI) do not have the same clinical outcome. A Total Body Irradiation
      induces an acute radiation syndrome with a Medullary Aplasia. A quick diagnostic would allow
      the optimization of the medical care.

      Nowadays, the analyse of the chromosome with two centromeres is the current norm to estimate
      the radiation dose, but this technique is time consuming, and not adapted to an emergency
      situation, and to a large population.

      The new genetic techniques could permit the quick radiation dosimetry diagnosis. The research
      of early exposition bio-markers seems to be of a major interest. These bio-markers would
      allow to rapidly define the radiations perceived by an exposed subject, before the apparition
      of the symptoms, and by the way, to conduct to a therapeutic strategy more adapted to the
      patient.

      In this purpose, the present study will need blood and urines samples of patients totally or
      partially exposed to radiations, according to their usual medical care.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Level of haematological and biochemical markers
time frame: Day 3
description: The following bio-markers levels will be calculated :
Blood count,
Pads,
Haemoglobin,
Serum iron,
Plasma urea,
Urinary urea
Total protein,
albumin
creatin kinase,
Aspartate Amino Transferase,
alkaline phosphatase,
Total cholesterol,
Triglycerides,
Plasma creatinine
Creatinine clearance,
Urinary creatinine
Blood glucose,
Citrulline,
erythropoietin,
Plasma amylase,
Myoglobin,
Troponin,
C reactive protein,
Rate of prothrombin,
Fibrinogen,
D-Dimer,
Factor-V,
Fms-like tyrosine kinase 3-Ligand.
measure: Quantification of chromosomal aberrations
time frame: Day 3
description: Quantification of chromosomal aberrations will be performed on the blood samples performed at days 0, 1, 2 and 3 after the beginning of the rays perform in the usual practice.
measure: Detection of biochemical markers
time frame: Day 3
description: The presence or absence of these markers will be notified:
Interleukin 1
Interleukin 6
Interleukin 8
Interleukin 18
Tumor Necrosis Factor alpha (TNF-alpha)
Brain-Derived Neurotrophic Factor (BDNF)
Granulocyte Colony-Stimulating Factor (G - CSF)
Serum amyloid A (SAA)
Growth Arrest and DNA Damage-inducible 45 (GADD45)
Intestinal-type Fatty Acid-Binding Protein (FABP-I)
Liver-type Fatty Acid-Binding Protein (L-FABP)
Heart-type Fatty Acid-Binding Protein (H-FABP)
Stem Cell Factor Receptor CD117
measure: Metabolomics markers levels
time frame: Day 2
description: The metabolomic levels of the following molecules will be calculated on urine samples:
3 - Sulfate Hydroxytyrosol
1, 6-Anhydro-beta-D-glucose
1 - Methylnicotinamide
2 - Hydroxyisobutyrate
3 - aminoisobutyrate
3 - hydroxyisovalerate
3 - Hydroxymandelate
3 - Indoxylsulfate
4 - Hydroxyphenylacetate
Acetate
Acetone
Adipic acid
Alanine
Betaine
Carnitine
Choline
Cis-Aconitate
Citrate
Creatine
Creatinine
dimethylamine
Ethanolamine
Formats
Glucose
Glycine
Glycolate
Hippurate
Histidine
Hypoxanthine
Isethionic acid
Lactate
Methanol
Methylamine
N, N-Dimethylglycine
N - Acetylserotonin sulfate
N - Acetyltaurine
O - Acetylcarnitine
O - Phosphocholine
Pi-methylhistidine
Pyroglutamate
Succinate
Tartrate
Tau-methylhistidine
Taurine
Threonine
trans-Aconitate
Trigonelline
Trimethylamine N-oxide
Tyramine sulfate
Tyrosine
Tyrosol sulfate
Uracil
Robert acid
Valine
Xanthine
measure: Total dose of radiation
time frame: Day 3
description: The total dose of radiation will be calculated for each patient and compared will the biologic results.
measure: Radiation field
time frame: Day 3
description: The radiation field will be define for each patient and compared with the biological results.
arm group label: Total Body Irradiation
arm group type: Experimental
description: Patient suffering from a malignant blood disease that requires a total body radiation, without (or prior to) a concomitant chemotherapy, according to the following protocol: 2x2 Gray per day, for 3 days. Blood and urines samples will be performed at days 0, 1, 2 and 3 of the treatment plan.
arm group label: Partial Body Irradiation
arm group type: Experimental
description: Patient with at least one bone metastasis localized at the pelvis and requiring partial body radiation therapy without associated chemotherapy, according to the following protocol: 4 Gray per day for 5 days will perform blood and urines samples at days 0, 1, 2 and 3 after the beginning of the radiation treatment.
intervention type: Other
intervention name: blood and urines samples
description: For all patients the blood samples must be organized: Before, 4 hours (+/-30 min), 1 day, 2 days, and 3 days after the start of the radiation therapy.
Collections of urine must be organized: Before, 1 day, and 2 days after the radiation therapy.
arm group label: Partial Body Irradiation
arm group label: Total Body Irradiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Nicolas Magné, PhD
role: Principal Investigator
affiliation: Institut de Cancérologie Lucien Neuwirth
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
sharing ipd: No