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

Primary Purpose

Myelodysplastic Syndrome, Acute Myeloid Leukemia

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Vitamin C

Placebo

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Rigshospitalet

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Vitamin C

Placebo

Arm Description

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

Oral intake of placebo tablet daily for 56 days

Outcomes

Primary Outcome Measures

Overall 5-hmC/5-mC ratio

Overall lysine methylation levels

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

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

Aberrant histone methylation associated with hematopoietic development

Aberrant histone methylation associated with ERVs

Expression levels of ERVs

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

ERV specific T-cell recognition in vivo

Secondary Outcome Measures

Full Information

NCT ID

NCT02877277

First Posted

August 9, 2016

Last Updated

September 20, 2018

Sponsor

Rigshospitalet, Denmark

Collaborators

Van Andel Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT02877277

Brief Title

Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study

Acronym

EVITA-Pilot

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

August 8, 2016 (Actual)

Primary Completion Date

May 29, 2017 (Actual)

Study Completion Date

May 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rigshospitalet, Denmark

Collaborators

Van Andel Research Institute

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndrome, Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vitamin C

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Oral intake of placebo tablet daily for 56 days

Intervention Type

Dietary Supplement

Intervention Name(s)

Vitamin C

Intervention Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

Oral intake of placebo tablet daily for 56 days

Primary Outcome Measure Information:

Title

Overall 5-hmC/5-mC ratio

Time Frame