Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study (EVITA-Pilot)

Rigshospitalet

Status: Completed

Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukemia

Treatments: Dietary Supplement: Placebo; Dietary Supplement: Vitamin C

Study type: Interventional

Funder types: Other

Identifiers

NCT02877277

H-16022249

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• MDS/AML patient in treatment with DNMTi

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups, including a placebo group

Vitamin C

Experimental group

Description:

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

Treatment:

Dietary Supplement: Vitamin C

Placebo

Placebo Comparator group

Description:

Oral intake of placebo tablet daily for 56 days

Treatment:

Dietary Supplement: Placebo