Validation of Radio-induced Damage Biomarkers (BIOM-DRI)

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

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.

Study Overview

• Status: Terminated
• Conditions: Bone Metastasis; Malignant Hemopathy
• Intervention / Treatment: Other: blood and urines samples

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Saint-Priest en Jarez, France, 42270
    • Institut de Cancérologie Lucien Neuwirth
  • Villejuif, France, 94800
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Total Body Irradiation; 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; 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.
Experimental: Partial Body Irradiation; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Institut de Cancérologie de la Loire; Institut de Recherche Biomedicale des Armees

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: September 21, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimate): December 21, 2016

Study Record Updates

• Last Update Posted (Actual): February 22, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Bio-markers; Radiation; Total Body Irradiation; Appropriate therapeutic strategy; Partial Body Irradiation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 2016-0901; 2016-A01446-45 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No