Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls

NCT02809222 | Completed

• 2 other identifiers: PHAO16-EG/PLASMYC2016-A00539-42
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 2

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.

Conditions

Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia

Keywords

Myelodysplastic syndrome; Ascorbic acid; Oxidative stress; Preleukemia

Outcome Measures

Primary Outcomes (1)

• Plasmatic ascorbic acid concentration at baseline

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

  month 0

Secondary Outcomes (10)

• Plasmatic ascorbic acid concentration during follow-up

  at 3 months, 6 months and 12 months

• Plasmatic antioxidants concentrations

  at 0 months, 6 months and 12 months

• Collection of plasma

  at 0 month, 3 months, 6 months and 12 months

• Complete blood count and blood blasts cells

  at 0 month, 3 months, 6 months and 12 months

• Polyunsaturated fatty acids

  at 0 month, 3 months, 6 months and 12 months

Study Arms (3)

Patients with MDS at diagnosis

OTHER

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; Other: Quality of life questionnaire

Patients with MDS in treatment

OTHER

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; Other: Quality of life questionnaire

Healthy volunteers

OTHER

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

Other: Samples

Interventions

Samples OTHER

Blood samples

Healthy volunteers; Patients with MDS at diagnosis; Patients with MDS in treatment

Quality of life questionnaire OTHER

Questionnaire to assess the quality of life of cancer patients

Also known as: EORTC QLQ-C30

Patients with MDS at diagnosis; Patients with MDS in treatment

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification
• Patient untreated by other means than blood transfusions
• Age ≥ 60 years
• Patient affiliated to social security scheme
• Informed consent signed by the patient

You may not qualify if:

• 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:
• 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
• Previous allogenic stem cell transplantation
• Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention

Sponsors & Collaborators

• University Hospital, Tours: lead
• Tours Autogreffe: collaborator
• Novartis: collaborator

Study Sites (2)

Clinical Research Center, University Hospital, Tours

Tours, 37044, France

Location

Department of Haematology and Cell Therapy, University Hospital, Tours

Tours, 3704, France

Location

Related Publications (13)

• 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.

  PMID: 21655231 BACKGROUND

• 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.

  PMID: 17976187 BACKGROUND

• 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.

  PMID: 21398578 BACKGROUND

• 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.

  PMID: 23958061 BACKGROUND

• 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. doi: 10.1001/jama.281.15.1415.

  PMID: 10217058 BACKGROUND

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

  PMID: 3362876 BACKGROUND

• 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.

  PMID: 1962577 BACKGROUND

• 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.

  PMID: 1643638 BACKGROUND

• 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.

  PMID: 19284416 BACKGROUND

• 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. doi: 10.1046/j.1365-2141.1998.01114.x.

  PMID: 9886323 BACKGROUND

• 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.

  PMID: 11090080 BACKGROUND

• 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. doi: 10.1034/j.1600-0609.2000.9l036.x. No abstract available.

  PMID: 10680708 BACKGROUND

• 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. No abstract available.

  PMID: 21815182 BACKGROUND

MeSH Terms

Conditions

Myelodysplastic Syndromes; Preleukemia

Interventions

Sampling Studies

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Precancerous Conditions; Neoplasms

Intervention Hierarchy (Ancestors)

Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Emmanuel GYAN, MD,PhD

  University Hospital, Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 22, 2016
• Study Start: October 25, 2016
• Primary Completion: March 3, 2020
• Study Completion: March 1, 2021
• Last Updated: April 19, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)