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NCT Number: NCT02809222

Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls

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.

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Key information

Age range

60 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Clinical Research Center, University Hospital, Tours, Tours, France

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

  • 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

Treatment and study plan

Samples

Other

Blood samples

Quality of Life Questionnaire

Other

Questionnaire to assess the quality of life of cancer patients

Other names: EORTC QLQ-C30

Primary outcomes

  1. Plasmatic ascorbic acid concentration at baseline

    Time frame: month 0

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

Secondary outcomes

  1. Plasmatic ascorbic acid concentration during follow-up

    Time frame: at 3 months, 6 months and 12 months

    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

  2. Plasmatic antioxidants concentrations

    Time frame: at 0 months, 6 months and 12 months

    For all groups: Plasmatic antioxidants concentrations at 0 months, 6 months and 12 months

  3. Collection of plasma

    Time frame: at 0 month, 3 months, 6 months and 12 months

    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

  4. Complete blood count and blood blasts cells

    Time frame: at 0 month, 3 months, 6 months and 12 months

    For patients MDS groups: Complete blood count and blood blasts cells at 0 month, 3 months, 6 months and 12 months

  5. Polyunsaturated fatty acids

    Time frame: at 0 month, 3 months, 6 months and 12 months

    For patients MDS groups: Polyunsaturated fatty acids at 0 month, 3 months, 6 months and 12 months

  6. Plasmatic ascorbic acid concentration and number of adverse events

    Time frame: at 3 months, 6 months and 12 months

    For patients MDS groups: Plasmatic ascorbic acid concentration at 3 months, 6 months and 12 months and number of adverse events during follow-up

  7. Oxidative stress parameters and number of adverse events

    Time frame: at 3 months, 6 months and 12 months

    For patients MDS groups: Oxidative stress parameters at 3 months, 6 months and 12 months and number of adverse events during follow-up

  8. Plasmatic ascorbic acid concentration and parameters of iron metabolism

    Time frame: at 0 month and 12 months

    For patients MDS groups: Plasmatic ascorbic acid concentration and parameters of iron metabolism at 0 month and 12 months

  9. Plasmatic ascorbic acid concentration and quality of life

    Time frame: at 0 month, 3 months, 6 months and 12 months

    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

  10. Collection of frozen cells

    Time frame: 0 month and in case of evolution of the disease

    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.

Sponsors and collaborators

Lead sponsor

University Hospital, Tours

Other

Collaborators

  • Novartis
  • Tours Autogreffe

Registry information

Official study title

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

Acronym: PLASMYC

Important dates

Study start
2016
Primary completion
2020
Study completion
2021
First posted
Jun 22, 2016
Registry last updated
Apr 19, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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