NCT02877277

Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Rigshospitalet, Denmark · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Vitamin C	Oral intake of vitamin C tablet (500 mg) daily for 56 days
DIETARY_SUPPLEMENT	Placebo	Oral intake of placebo tablet daily for 56 days

Timeline

• Start date: 2016-08-08
• Primary completion: 2017-05-29
• Completion: 2017-05-29
• First posted: 2016-08-24
• Last updated: 2018-09-24

Locations

1 site across 1 country: Denmark