Validation of Radio-induced Damage Biomarkers

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Validation of Radio-induced Damage Biomarkers : BIOM-DRI Study

Conditions
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Bone Metastasis, Malignant Hemopathy

Intervention / Treatment
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* Other: blood and urines samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: More than 18 years old For the group A: Patient suffering from a malignant blood disease requiring a whole-body radiation, without (or prior to) a concomitant chemotherapy, according to the following protocol: 2x2 Gray per day, during 3 days. OR For the group B: Patient with one (or more) pelvis metastasis requiring radiation therapy without concomitant chemotherapy, according to the following protocol: 4 Gray per day for 5 days. Exclusion Criteria: More than 70 years old, Subject presenting abnormal blood count (grade 3), Person with a not controlled chronic illness, Subject presenting an abnormal hepatic assessment (grade 3), Subject having already received ionizing treatments, Subject reached HIV, hepatitis C or any other progressive infectious diseases, Pregnant women or nursing mothers, Person under protection of justice or unable to give consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total Body Irradiation<br>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. | Other: blood and urines samples<br>* 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.<br>|
| Experimental: Partial Body Irradiation<br>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. | Other: blood and urines samples<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of haematological and biochemical markers | 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. | Day 3 | 
| Quantification of chromosomal aberrations | 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. | Day 3 | 
| Detection of biochemical markers | 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 | Day 3 | 
| Metabolomics markers levels | 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 | Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total dose of radiation | The total dose of radiation will be calculated for each patient and compared will the biologic results. | Day 3 | 
| Radiation field | The radiation field will be define for each patient and compared with the biological results. | Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bio-markers, Radiation, Appropriate therapeutic strategy, Total Body Irradiation, Partial Body Irradiation