Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls

Myelodysplastic Syndrome Clinical Trial

— PLASMYC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02809222
• Other study ID #: PHAO16-EG/PLASMYC
• Secondary ID: 2016-A00539-42
• Status: Completed
• Phase: N/A
• Start date: October 25, 2016
• Est. completion date: March 1, 2021

Study information

• Verified date: April 2021
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: March 1, 2021
• Est. primary completion date: March 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Secondary Acute Myeloid Leukemia
• Syndrome

Intervention

Other:
• Samples
Blood samples
• Quality of life questionnaire
Questionnaire to assess the quality of life of cancer patients

Locations

Country	Name	City	State
France	Clinical Research Center, University Hospital, Tours	Tours
France	Department of Haematology and Cell Therapy, University Hospital, Tours	Tours

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Tours	Novartis, Tours Autogreffe

Country where clinical trial is conducted

France, 

References & Publications (13)

Chung YJ, Robert C, Gough SM, Rassool FV, Aplan PD. Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome. Leuk Res. 2014 Jan;38(1):95-102. doi: 10.1016/j.leukres.2013.07.008. Epub 2013 Aug 16. — View Citation

Das A, Dey N, Ghosh A, Das T, Chatterjee IB. NAD(P)H: quinone oxidoreductase 1 deficiency conjoint with marginal vitamin C deficiency causes cigarette smoke induced myelodysplastic syndromes. PLoS One. 2011;6(5):e20590. doi: 10.1371/journal.pone.0020590. Epub 2011 May 31. — View Citation

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. Epub 2007 Nov 1. — View Citation

Hole PS, Darley RL, Tonks A. Do reactive oxygen species play a role in myeloid leukemias? Blood. 2011 Jun 2;117(22):5816-26. doi: 10.1182/blood-2011-01-326025. Epub 2011 Mar 11. Review. Erratum in: Blood. 2014 Jan 30;123(5):798. — View Citation

Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999 Apr 21;281(15):1415-23. — View Citation

Park CH, Kimler BF, Bodensteiner D, Lynch SR, Hassanein RS. In vitro growth modulation by L-ascorbic acid of colony-forming cells from bone marrow of patients with myelodysplastic syndromes. Cancer Res. 1992 Aug 15;52(16):4458-66. — View Citation

Park CH, Kimler BF, Yi SY, Park SH, Kim K, Jung CW, Kim SH, Lee ER, Rha M, Kim S, Park MH, Lee SJ, Park HK, Lee MH, Yoon SS, Min YH, Kim BS, Kim JA, Kim WS. Depletion of L-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes. Eur J Haematol. 2009 Aug;83(2):108-18. doi: 10.1111/j.1600-0609.2009.01252.x. Epub 2009 Mar 5. — View Citation

Park CH, Kimler BF. Growth modulation of human leukemic, preleukemic, and myeloma progenitor cells by L-ascorbic acid. Am J Clin Nutr. 1991 Dec;54(6 Suppl):1241S-1246S. doi: 10.1093/ajcn/54.6.1241s. — View Citation

Park CH. Vitamin C in leukemia and preleukemia cell growth. Prog Clin Biol Res. 1988;259:321-30. — View Citation

Parker JE, Fishlock KL, Mijovic A, Czepulkowski B, Pagliuca A, Mufti GJ. 'Low-risk' myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro- versus anti-apoptotic bcl-2-related proteins. Br J Haematol. 1998 Dec;103(4):1075-82. — View Citation

Parker JE, Mufti GJ, Rasool F, Mijovic A, Devereux S, Pagliuca A. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood. 2000 Dec 1;96(12):3932-8. — View Citation

Saito N, Miyamoto M, Gotoh U, Yoshitomi S. Effect of biscoclaurine alkaloids, prednisolone and ascorbic acid on myelodysplastic syndrome with pancytopenia: a case report. Eur J Haematol. 2000 Jan;64(1):61-5. — View Citation

Welch JS, Klco JM, Gao F, Procknow E, Uy GL, Stockerl-Goldstein KE, Abboud CN, Westervelt P, DiPersio JF, Hassan A, Cashen AF, Vij R. Combination decitabine, arsenic trioxide, and ascorbic acid for the treatment of myelodysplastic syndrome and acute myeloid leukemia: a phase I study. Am J Hematol. 2011 Sep;86(9):796-800. doi: 10.1002/ajh.22092. Epub 2011 Aug 3. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasmatic ascorbic acid concentration at baseline	For all groups: Plasmatic ascorbic acid concentration at first visit (0 month)	month 0
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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