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

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ClinicalTrials.gov Identifier: NCT02877277
Recruitment Status : Completed
First Posted : August 24, 2016
Last Update Posted : September 24, 2018
Sponsor:
Collaborator:
Van Andel Research Institute
Information provided by (Responsible Party):
Kirsten Grønbæk, Rigshospitalet, Denmark

Tracking Information
First Submitted Date  ICMJE August 9, 2016
First Posted Date  ICMJE August 24, 2016
Last Update Posted Date September 24, 2018
Actual Study Start Date  ICMJE August 8, 2016
Actual Primary Completion Date May 29, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
  • Overall 5-hmC/5-mC ratio [ Time Frame: Change from baseline to day 84 ]
  • Overall lysine methylation levels [ Time Frame: Change from baseline to day 84 ]
  • 5-hmC/5-mC ratio at regulatory genomic regions of genes involved in hematopoietic development [ Time Frame: Change from baseline to day 84 ]
  • Accumulation of 5-hmC/5-mC at regulatory regions of ERVs [ Time Frame: Change from baseline to day 84 ]
  • Aberrant histone methylation associated with hematopoietic development [ Time Frame: Change from baseline to day 84 ]
  • Aberrant histone methylation associated with ERVs [ Time Frame: Change from baseline to day 84 ]
  • Expression levels of ERVs [ Time Frame: Change from baseline to day 84 ]
  • Activity of the viral defense pathway measured by RNA and protein expression [ Time Frame: Change from baseline to day 84 ]
  • ERV specific T-cell recognition in vivo [ Time Frame: Change from baseline to day 84 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02877277 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study
Official Title  ICMJE Restoring Physiological Vitamin C Levels to the Normal Range: Influence on Epigenetic Regulation in Normal and Malignant Hematopoiesis
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodysplastic Syndrome
  • Acute Myeloid Leukemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Vitamin C
    Oral intake of vitamin C tablet (500 mg) daily for 56 days
    Intervention: Dietary Supplement: Vitamin C
  • Placebo Comparator: Placebo
    Oral intake of placebo tablet daily for 56 days
    Intervention: Dietary Supplement: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 18, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 29, 2017
Actual Primary Completion Date May 29, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • MDS/AML patient in treatment with DNMTi

Exclusion Criteria:

  • Intake of vitamin C as a dietary supplement including multivitamin
  • Non-compliance
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02877277
Other Study ID Numbers  ICMJE H-16022249
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kirsten Grønbæk, Rigshospitalet, Denmark
Study Sponsor  ICMJE Rigshospitalet, Denmark
Collaborators  ICMJE Van Andel Research Institute
Investigators  ICMJE
Principal Investigator: Kirsten Grønbæk, Professor Rigshospitalet, Denmark
PRS Account Rigshospitalet, Denmark
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP