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Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls (PLASMYC)

Primary Purpose

Myelodysplastic Syndrome, Secondary Acute Myeloid Leukemia

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Samples
Quality of life questionnaire
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Myelodysplastic Syndrome focused on measuring Myelodysplastic syndrome, Ascorbic acid, Oxidative stress, Preleukemia

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

  1. 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

  2. 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
  3. 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

Sites / Locations

  • Clinical Research Center, University Hospital, Tours
  • Department of Haematology and Cell Therapy, University Hospital, Tours

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Patients with MDS at diagnosis

Patients with MDS in treatment

Healthy volunteers

Arm Description

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

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

The intervention, specific to the study, is to take blood samples on patients healthy volunteers.

Outcomes

Primary Outcome Measures

Plasmatic ascorbic acid concentration at baseline
For all groups: Plasmatic ascorbic acid concentration at first visit (0 month)

Secondary Outcome Measures

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
Plasmatic antioxidants concentrations
For all groups: Plasmatic antioxidants concentrations 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
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
Polyunsaturated fatty acids
For patients MDS groups: Polyunsaturated fatty acids 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
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
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
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
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.

Full Information

First Posted
June 17, 2016
Last Updated
April 15, 2021
Sponsor
University Hospital, Tours
Collaborators
Tours Autogreffe, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT02809222
Brief Title
Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls
Acronym
PLASMYC
Official Title
Kinetics of the Plasmatic Concentration of L-Ascorbic Acid in Patient With Myelodysplastic Syndromes and Control Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
October 25, 2016 (Actual)
Primary Completion Date
March 3, 2020 (Actual)
Study Completion Date
March 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours
Collaborators
Tours Autogreffe, Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome, Secondary Acute Myeloid Leukemia
Keywords
Myelodysplastic syndrome, Ascorbic acid, Oxidative stress, Preleukemia

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
138 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients with MDS at diagnosis
Arm Type
Other
Arm Description
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
Arm Title
Patients with MDS in treatment
Arm Type
Other
Arm Description
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
Arm Title
Healthy volunteers
Arm Type
Other
Arm Description
The intervention, specific to the study, is to take blood samples on patients healthy volunteers.
Intervention Type
Other
Intervention Name(s)
Samples
Intervention Description
Blood samples
Intervention Type
Other
Intervention Name(s)
Quality of life questionnaire
Other Intervention Name(s)
EORTC QLQ-C30
Intervention Description
Questionnaire to assess the quality of life of cancer patients
Primary Outcome Measure Information:
Title
Plasmatic ascorbic acid concentration at baseline
Description
For all groups: Plasmatic ascorbic acid concentration at first visit (0 month)
Time Frame
month 0
Secondary Outcome Measure Information:
Title
Plasmatic ascorbic acid concentration during follow-up
Description
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
Time Frame
at 3 months, 6 months and 12 months
Title
Plasmatic antioxidants concentrations
Description
For all groups: Plasmatic antioxidants concentrations at 0 months, 6 months and 12 months
Time Frame
at 0 months, 6 months and 12 months
Title
Collection of plasma
Description
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
Time Frame
at 0 month, 3 months, 6 months and 12 months
Title
Complete blood count and blood blasts cells
Description
For patients MDS groups: Complete blood count and blood blasts cells at 0 month, 3 months, 6 months and 12 months
Time Frame
at 0 month, 3 months, 6 months and 12 months
Title
Polyunsaturated fatty acids
Description
For patients MDS groups: Polyunsaturated fatty acids at 0 month, 3 months, 6 months and 12 months
Time Frame
at 0 month, 3 months, 6 months and 12 months
Title
Plasmatic ascorbic acid concentration and number of adverse events
Description
For patients MDS groups: Plasmatic ascorbic acid concentration at 3 months, 6 months and 12 months and number of adverse events during follow-up
Time Frame
at 3 months, 6 months and 12 months
Title
Oxidative stress parameters and number of adverse events
Description
For patients MDS groups: Oxidative stress parameters at 3 months, 6 months and 12 months and number of adverse events during follow-up
Time Frame
at 3 months, 6 months and 12 months
Title
Plasmatic ascorbic acid concentration and parameters of iron metabolism
Description
For patients MDS groups: Plasmatic ascorbic acid concentration and parameters of iron metabolism at 0 month and 12 months
Time Frame
at 0 month and 12 months
Title
Plasmatic ascorbic acid concentration and quality of life
Description
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
Time Frame
at 0 month, 3 months, 6 months and 12 months
Title
Collection of frozen cells
Description
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.
Time Frame
0 month and in case of evolution of the disease

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emmanuel GYAN, MD,PhD
Organizational Affiliation
University Hospital, Tours
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Research Center, University Hospital, Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Department of Haematology and Cell Therapy, University Hospital, Tours
City
Tours
ZIP/Postal Code
3704
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21655231
Citation
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Results Reference
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Ghoti H, Amer J, Winder A, Rachmilewitz E, Fibach E. Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome. Eur J Haematol. 2007 Dec;79(6):463-7. doi: 10.1111/j.1600-0609.2007.00972.x. Epub 2007 Nov 1.
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Citation
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Citation
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PubMed Identifier
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Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls

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