Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls

Study Overview
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Brief Summary
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Myelodysplastic syndromes (MDS) is a group of heterogeneous diseases characterised by the clonal evolution of dysplastic hematopoietic stem cells. This evolution is associated with accumulation of cytogenetic mutations which leads to acute myeloid leukaemia (AML). Evolution of MDS is also associated with increase of reactive oxygen species (ROS). The increase of ROS is associated with accumulation of cytogenetic mutations. Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body. Studies showed that supplementation with AA can change the proliferation status of MDS cells. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients with myelodysplastic syndromes advanced in their treatment or recently diagnosed during a follow-up of 12 months.

Detailed Description
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Myelodysplastic syndromes (MDS) is a group of heterogeneous life threatening diseases characterised by the clonal evolution of dysplastic myeloid hematopoietic stem cells. This evolution is initially associated with an excess of apoptosis followed by an excess of proliferation then, after accumulation of cytogenetic mutations, a transformation in acute myeloid leukaemia (AML) can appear. Evolution of MDS is also associated with increase of reactive oxygen species (ROS) . In MDS mice, perturbations of the metabolism of ROS is associated with increases in the number of cytogenetic mutations. Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body. In vitro studies showed that supplementation with AA can change the proliferation status of MDS cells . Guinea pigs with a phenotype with excess of ROS supplemented with AA have less somatic mutations and less MDS. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML. To our knowledge no study have demonstrated the variations of the parameters of the oxidative metabolism during the evolution of MDS. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients diagnosed with MDS in treatment or recently diagnosed during a follow-up of 12 months. During the follow-up a collection of plasma from volunteers and patients will be created for later analysis.

Official Title
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Kinetics of the Plasmatic Concentration of L-Ascorbic Acid in Patient With Myelodysplastic Syndromes and Control Subjects

Conditions
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Myelodysplastic Syndrome, Secondary Acute Myeloid Leukemia

Intervention / Treatment
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* Other: Samples
* Other: Quality of life questionnaire


Participation Criteria
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Eligibility Criteria
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Patients MDS at diagnosis group selection criteria Inclusion Criteria: Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification Patient diagnosed for less than 4 months before inclusion Patient untreated by other means than blood transfusions Age ≥ 60 years Patient affiliated to social security scheme Informed consent signed by the patient Exclusion Criteria: Previous allogenic stem cell transplantation Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention Active inflammatory disease Patient under legal protection measure Patient unwilling or who cannot submit to prospective biological follow-up Patients MDS in treatment group selection criteria: Inclusion Criteria: Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification Patient not included in patients MDS at diagnosis group Patient diagnosed for more than 12 months Treated with hypomethylating agents and/or erythropoiesis-stimulating agents and/or blood transfusions. Age ≥ 60 years Patient affiliated to social security scheme Informed consent signed by the patient Exclusion Criteria: Previous allogenic stem cell transplantation Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention Active inflammatory disease Patient under legal protection measure Patient unwilling or who cannot submit to prospective biological follow-up Healthy volunteers group selection criteria: Inclusion Criteria: Age ≥ 60 years Patient affiliated to social security scheme Informed consent signed by the patient Exclusion Criteria: History of another primary malignancy that is currently clinically significant or currently requires active intervention History of active inflammatory diseases Volunteer under legal protection measure Volunteer unwilling or who cannot submit to prospective biological follow-up

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients with MDS at diagnosis<br>The intervention, specific to the study, is to take blood samples on patients with MDS at diagnosis. A quality of life questionnaire will also be used to monitor patients | Other: Samples<br>* Blood samples<br>Other: Quality of life questionnaire<br>* Questionnaire to assess the quality of life of cancer patients<br>* Other names: EORTC QLQ-C30;|
| Other: Patients with MDS in treatment<br>The intervention, specific to the study, is to take blood samples on patients with MDS receiving treatment. A quality of life questionnaire will also be used to monitor patients | Other: Samples<br>* Blood samples<br>Other: Quality of life questionnaire<br>* Questionnaire to assess the quality of life of cancer patients<br>* Other names: EORTC QLQ-C30;|
| Other: Healthy volunteers<br>The intervention, specific to the study, is to take blood samples on patients healthy volunteers. | Other: Samples<br>* Blood samples<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasmatic ascorbic acid concentration at baseline | For all groups: Plasmatic ascorbic acid concentration at first visit (0 month) | month 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasmatic ascorbic acid concentration during follow-up | For all groups: Plasmatic ascorbic acid concentrations at 6 months and 12 months visits with an extra plasmatic ascorbic acid concentrations at 3 months for patients MDS groups | at 3 months, 6 months and 12 months | 
| Plasmatic antioxidants concentrations | For all groups: Plasmatic antioxidants concentrations at 0 months, 6 months and 12 months | at 0 months, 6 months and 12 months | 
| Collection of plasma | For all groups: Creation of a collection of plasma samples for later analysis at 0 month, 6 months and 12 months with an extra plasma sample at 3 months for patients MDS groups | at 0 month, 3 months, 6 months and 12 months | 
| Complete blood count and blood blasts cells | For patients MDS groups: Complete blood count and blood blasts cells at 0 month, 3 months, 6 months and 12 months | at 0 month, 3 months, 6 months and 12 months | 
| Polyunsaturated fatty acids | For patients MDS groups: Polyunsaturated fatty acids at 0 month, 3 months, 6 months and 12 months | at 0 month, 3 months, 6 months and 12 months | 
| Plasmatic ascorbic acid concentration and number of adverse events | For patients MDS groups: Plasmatic ascorbic acid concentration at 3 months, 6 months and 12 months and number of adverse events during follow-up | at 3 months, 6 months and 12 months | 
| Oxidative stress parameters and number of adverse events | For patients MDS groups: Oxidative stress parameters at 3 months, 6 months and 12 months and number of adverse events during follow-up | at 3 months, 6 months and 12 months | 
| Plasmatic ascorbic acid concentration and parameters of iron metabolism | For patients MDS groups: Plasmatic ascorbic acid concentration and parameters of iron metabolism at 0 month and 12 months | at 0 month and 12 months | 
| Plasmatic ascorbic acid concentration and quality of life | For patients MDS groups: Plasmatic ascorbic acid concentration and quality of life evaluated by the EORTC QLQ-C30 3rd version at 0 month, 3 months, 6 months and 12 months | at 0 month, 3 months, 6 months and 12 months | 
| Collection of frozen cells | For patients MDS groups: Creation of a collection of frozen cells for DNA analysis at 0 month and in case of evolution of the disease. | 0 month and in case of evolution of the disease | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic syndrome, Ascorbic acid, Oxidative stress, Preleukemia