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Completed

NCT Number: NCT02877277

Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study

This study evaluates whether vitamin C improves responses to epigenetic therapy with DNMTis. Half of the patients will receive vitamin C and DNMTi while the other half will receive placebo and DNMTi.

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Key information

Conditions

Myelodysplastic Syndrome Acute Myeloid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Rigshospitalet

København Ø, 2100, Denmark

About this study

Recently, it was documented that hematological cancer patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) exhibited severe vitamin C deficiency. Vitamin C is an essential co-factor for ten-eleven translocation (TET) enzymes, which initiate DNA demethylation through oxidation of 5-methylcytosine (mC) to 5-hydroxy-methylcytosine (hmC). In-vitro studies show that vitamin C at physiological doses added to DNA methyltransferase inhibitors (DNMTis), induce a synergistic inhibition of cell proliferation and enhanced apoptosis. These effects are mediated via a viral mimicry response recently associated with cancer stem-like cell death and enhanced immune signals including increased expression of bi-directionally transcribed endogenous retrovirus (ERV) transcripts, increased presence of cytosolic double stranded RNAs, and activation of an interferon inducing cellular response to these transcripts. Data suggest that correction of vitamin C deficiency may improve responses to epigenetic therapy with DNMTis. In the EVITA pilot study, the investigators include MDS/AML patients and explore the potential role of restoring vitamin C within the normal physiological range in treatment of hematological cancer with DNMTis.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • MDS/AML patient in treatment with DNMTi

Exclusion criteria

  • Intake of vitamin C as a dietary supplement including multivitamin
  • Non-compliance

Treatment and study plan

Vitamin C

Dietary Supplement

Oral intake of vitamin C tablet (500 mg) daily for 56 days

Placebo

Dietary Supplement

Oral intake of placebo tablet daily for 56 days

Primary outcomes

  1. Overall 5-hmC/5-mC ratio

    Time frame: Change from baseline to day 84

  2. Overall lysine methylation levels

    Time frame: Change from baseline to day 84

  3. 5-hmC/5-mC ratio at regulatory genomic regions of genes involved in hematopoietic development

    Time frame: Change from baseline to day 84

  4. Accumulation of 5-hmC/5-mC at regulatory regions of ERVs

    Time frame: Change from baseline to day 84

  5. Aberrant histone methylation associated with hematopoietic development

    Time frame: Change from baseline to day 84

  6. Aberrant histone methylation associated with ERVs

    Time frame: Change from baseline to day 84

  7. Expression levels of ERVs

    Time frame: Change from baseline to day 84

  8. Activity of the viral defense pathway measured by RNA and protein expression

    Time frame: Change from baseline to day 84

  9. ERV specific T-cell recognition in vivo

    Time frame: Change from baseline to day 84

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Collaborators

  • Van Andel Research Institute

Registry information

Official study title

Restoring Physiological Vitamin C Levels to the Normal Range: Influence on Epigenetic Regulation in Normal and Malignant Hematopoiesis

Acronym: EVITA-Pilot

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Aug 24, 2016
Registry last updated
Sep 24, 2018

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

View the official ClinicalTrials.gov record (opens in a new tab)

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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