Epigenetics, Vitamin C, and Abnormal Blood Cell Formation - Vitamin C in Patients With Low-Risk Myeloid Malignancies (EVITA)
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ClinicalTrials.gov Identifier: NCT03682029 |
Recruitment Status :
Recruiting
First Posted : September 24, 2018
Last Update Posted : August 19, 2020
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Condition or disease | Intervention/treatment | Phase |
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Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia-1 Cytopenia | Dietary Supplement: Vitamin C (ascorbic acid) Other: Placebo | Not Applicable |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 100 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Prospective, randomized, placebo-controlled trial. |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Randomization performed by the independent provider of study medication (Glostrup Pharmacy). |
Primary Purpose: | Prevention |
Official Title: | Epigenetics, Vitamin C, and Abnormal Hematopoiesis - Role of Vitamin C in Epigenetic Regulation in Hematopoiesis Sub-Study on CCUS, Low-Risk MDS, and CMML-0/1 |
Actual Study Start Date : | November 21, 2017 |
Estimated Primary Completion Date : | December 1, 2022 |
Estimated Study Completion Date : | December 1, 2022 |

Arm | Intervention/treatment |
---|---|
Experimental: Vitamin C
Vitamin C (ascorbic acid) 500 mg/capsule. Ingestion of 2 capsules (1000 mg) daily for 12 months.
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Dietary Supplement: Vitamin C (ascorbic acid)
Monotherapy with oral vitamin C supplementation to elevate plasma vitamin C level to the upper end of the physiological range. |
Placebo Comparator: Placebo
Placebo capsule. Ingestion of 2 capsules daily for 12 months. Placebo will be prepared as capsules that look and taste identical to the vitamin C supplement capsules. The content of the placebo is lactose, potato starch, gelatin, magnesium stearate, and talc.
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Other: Placebo
Placebo |
- Median Change from Baseline in Variant Allele Frequency at 12 Months [ Time Frame: At baseline and at 12 months ]Median change from baseline to 12 months in mutant allele burden as measured by the variant allele frequency (VAF) and number of mutations in the vitC group vs. the placebo group.
- Mean Change from Baseline in 5-hmC/5-mC Level at 3 Months and 12 months [ Time Frame: At baseline and at 3 months and 12 months ]Mean change from baseline to 3 months and 12 months in global 5-hmC/5-mC measured in hematopoietic stem cells is compared between the vitamin C group and the placebo group. In addition, the mean change from baseline in 5-hmC/5-mC at 12 months is compared between participants in the vitamin C arm with baseline plasma vitamin C level in the normal range vs. participants in the vitamin C arm with baseline plasma vitamin C level below the normal range.
- Mean Change from Baseline in 5-mC at Selected Sites at 12 Months [ Time Frame: At baseline and at 12 months ]Mean change from baseline to 12 months in 5-mC at promoters/enhancers/long terminal repeats, and other regulatory genomic regions of tumor suppressors/methylated driver genes/genes involved in hematopoietic development.
- Mean Change from Baseline in H3K9 Methylation at Selected Sites at 12 Months [ Time Frame: At baseline and at 12 months ]Mean change from baseline to 12 months in methylated histone H3 lysine at position 9 at promoters/enhancers/long terminal repeats, and other regulatory regions of tumor suppressors/methylated driver genes/genes involved in hematopoietic development.
- Mean Change from Baseline in Plasma Cytokine Levels at 12 Months [ Time Frame: At baseline and at 12 months ]Mean change from baseline to 12 months in plasma cytokine levels (e.g., IL-6, S100A9, etc.).
- Mean Change from Baseline in mRNA Levels of Selected Genes at 12 Months [ Time Frame: At baseline and at 12 months ]Mean change from baseline to 12 months in mRNA levels of tumor suppressor genes, oncogenes, epigenetic regulators, cytokines, and genes involved in hematopoietic development.
- Mean Change from Baseline in mRNA Levels of Selected Genes at 3 Months [ Time Frame: At baseline and at 3 months ]Mean change from baseline to 3 months in mRNA levels of tumor suppressor genes, oncogenes, epigenetic regulators, cytokines, and genes involved in hematopoietic development.
- Number of Participants with Serious Adverse Events and Treatment-Related Adverse Events as Assessed by CTCAE v5.0 [ Time Frame: Through study completion, 12 months ]Number of serious adverse events and treatment-related adverse events as assessed by CTCAE v5.0. Adverse events, that are not considered serious or related to vitamin C intake, will not be recorded.
- Percentage of Participants with Vitamin C Deficiency [ Time Frame: Day 1 ]Percentage of participants with baseline plasma vitamin C level below the normal physiological range.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
A diagnosis of CCUS:
- Persistent cytopenia for > 6 months defined as hgb < 11.3 g/dL (7 mmol/L) in women and hgb < 12.9 g/dL (8 mmol/L) in men, thrombocyte count < 150 x 10^9/L or neutrophil count < 1.8 x 10^9/L
- Normal cytogenetics (with the exception of deletion of the Y chromosome which can be accepted)
- A bone marrow morphology that is not diagnostic of MDS or any other malignancy
- Other common causes of cytopenia (vitamin or other deficiencies, virus infection, etc.) have been ruled out
- Hematolytic conditions have been ruled out
- The presence of a detectable mutation in genes recurrently affected in myeloid malignancy representing a clonal marker (excluding germline mutations)
OR
A diagnosis of MDS as according to World Health Organization (WHO) 2016 diagnostic criteria
• Revised international prognostic scoring system (IPSS-R) risk score ≤ 3 AND bone marrow blast percentage < 5 defining low-risk
OR
A diagnosis of CMML-0 or -1 as according to WHO 2016 diagnostic criteria
AND
(All diagnostic categories) The presence of a detectable mutation in genes recurrently affected in myeloid malignancy representing a clonal marker (excluding germline mutations)
Exclusion Criteria:
- Unwillingness to discontinue any and all use of vitamin C medication/supplementation including multivitamin at least 24 hours prior to Baseline investigations and sampling
- Lack of ability to understand the information given, or lack of willingness to sign a written informed consent document
- Treatment with chemotherapy within the past 6 months
- Patients receiving active treatment for their myeloid malignancy, including investigational agents, with the exception of granulocyte colony-stimulating factor (G-CSF) and erythropoietin
- History of allergic reactions to ascorbic acid
- Unwillingness to comply with all aspects of the protocol

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03682029
Contact: Kirsten Grønbæk, Professor | +4535456060 | Kirsten.Groenbaek@regionh.dk | |
Contact: Stine Ulrik Mikkelsen, MD | +4535456071 | stine.ulrik.mikkelsen@regionh.dk |
United States, California | |
Keck Hospital of University of Southern California | Recruiting |
Los Angeles, California, United States, 90033 | |
Contact: Casey O'Connell, MD, FACP 323-865-3105 oconnell_c@med.usc.edu | |
Contact: Ibrahim Syed +1 323 226 4182 isyed@med.usc.edu | |
Principal Investigator: Casey O'Connell, MD | |
Denmark | |
Rigshospitalet | Recruiting |
Copenhagen, N/A = Not Applicable, Denmark, 2100 | |
Contact: Kirsten Grønbæk, Professor +4535456060 Kirsten.Groenbaek@regionh.dk | |
Contact: Stine Ulrik Mikkelsen, MD +4535456071 stine.ulrik.mikkelsen@regionh.dk | |
Sub-Investigator: Stine Ulrik Mikkelsen, MD | |
Principal Investigator: Kirsten Grønbæk, Professor | |
Sub-Investigator: Amalie B Nielsen, MD | |
Aalborg University Hospital | Not yet recruiting |
Aalborg, Denmark | |
Contact: Marianne T Severinsen, MD | |
Herlev University Hospital | Recruiting |
Copenhagen, Denmark, 2730 | |
Contact: Bo Mortensen, MD, PhD +4538686483 bo.kok.mortensen@regionh.dk | |
Principal Investigator: Bo Mortensen, MD, PhD | |
Odense University Hospital | Not yet recruiting |
Odense, Denmark | |
Contact: Klas Raaschou-Jensen, MD |
Principal Investigator: | Kirsten Grønbæk, Professor | Rigshospitalet, Denmark |
Publications:
Responsible Party: | Kirsten Grønbæk, Professor, MD, DMSc, Rigshospitalet, Denmark |
ClinicalTrials.gov Identifier: | NCT03682029 |
Other Study ID Numbers: |
H-16022249 low-risk cohort |
First Posted: | September 24, 2018 Key Record Dates |
Last Update Posted: | August 19, 2020 |
Last Verified: | August 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Clonal Cytopenia of Undetermined Significance Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia Low-Risk Myeloid Malignancies Vitamin C |
Epigenetics TET2 Randomized, Placebo-Controlled Trial Clinical Study |
Preleukemia Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Myelodysplastic Syndromes Leukemia Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Leukemia, Myeloid |
Myelodysplastic-Myeloproliferative Diseases Ascorbic Acid Vitamins Micronutrients Nutrients Growth Substances Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents |