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
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome
Eligibility Criteria
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
No
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
Change from baseline to day 84
Title
Overall lysine methylation levels
Time Frame
Change from baseline to day 84
Title
5-hmC/5-mC ratio at regulatory genomic regions of genes involved in hematopoietic development
Time Frame
Change from baseline to day 84
Title
Accumulation of 5-hmC/5-mC at regulatory regions of ERVs
Time Frame
Change from baseline to day 84
Title
Aberrant histone methylation associated with hematopoietic development
Time Frame
Change from baseline to day 84
Title
Aberrant histone methylation associated with ERVs
Time Frame
Change from baseline to day 84
Title
Expression levels of ERVs
Time Frame
Change from baseline to day 84
Title
Activity of the viral defense pathway measured by RNA and protein expression
Time Frame
Change from baseline to day 84
Title
ERV specific T-cell recognition in vivo
Time Frame
Change from baseline to day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
MDS/AML patient in treatment with DNMTi
Exclusion Criteria:
Intake of vitamin C as a dietary supplement including multivitamin
Non-compliance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kirsten Grønbæk, Professor
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rigshospitalet
City
København Ø
ZIP/Postal Code
2100
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31623675
Citation
Gillberg L, Orskov AD, Nasif A, Ohtani H, Madaj Z, Hansen JW, Rapin N, Mogensen JB, Liu M, Dufva IH, Lykkesfeldt J, Hajkova P, Jones PA, Gronbaek K. Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes. Clin Epigenetics. 2019 Oct 17;11(1):143. doi: 10.1186/s13148-019-0739-5.
Results Reference
derived
Learn more about this trial
Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study
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