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Trial record 1 of 1 for:    NCT02877277
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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

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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Acute Myeloid Leukemia Dietary Supplement: Vitamin C Dietary Supplement: Placebo Not Applicable

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 : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Restoring Physiological Vitamin C Levels to the Normal Range: Influence on Epigenetic Regulation in Normal and Malignant Hematopoiesis
Actual Study Start Date : August 8, 2016
Actual Primary Completion Date : May 29, 2017
Actual Study Completion Date : May 29, 2017


Arm Intervention/treatment
Experimental: Vitamin C
Oral intake of vitamin C tablet (500 mg) daily for 56 days
Dietary Supplement: Vitamin C
Oral intake of vitamin C tablet (500 mg) daily for 56 days

Placebo Comparator: Placebo
Oral intake of placebo tablet daily for 56 days
Dietary Supplement: Placebo
Oral intake of placebo tablet daily for 56 days




Primary Outcome Measures :
  1. Overall 5-hmC/5-mC ratio [ Time Frame: Change from baseline to day 84 ]
  2. Overall lysine methylation levels [ Time Frame: Change from baseline to day 84 ]
  3. 5-hmC/5-mC ratio at regulatory genomic regions of genes involved in hematopoietic development [ Time Frame: Change from baseline to day 84 ]
  4. Accumulation of 5-hmC/5-mC at regulatory regions of ERVs [ Time Frame: Change from baseline to day 84 ]
  5. Aberrant histone methylation associated with hematopoietic development [ Time Frame: Change from baseline to day 84 ]
  6. Aberrant histone methylation associated with ERVs [ Time Frame: Change from baseline to day 84 ]
  7. Expression levels of ERVs [ Time Frame: Change from baseline to day 84 ]
  8. Activity of the viral defense pathway measured by RNA and protein expression [ Time Frame: Change from baseline to day 84 ]
  9. ERV specific T-cell recognition in vivo [ Time Frame: Change from baseline to day 84 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • MDS/AML patient in treatment with DNMTi

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02877277


Locations
Denmark
Rigshospitalet
København Ø, Denmark, 2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Van Andel Research Institute
Investigators
Principal Investigator: Kirsten Grønbæk, Professor Rigshospitalet, Denmark

Responsible Party: Kirsten Grønbæk, Professor, MD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02877277     History of Changes
Other Study ID Numbers: H-16022249
First Posted: August 24, 2016    Key Record Dates
Last Update Posted: September 24, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Vitamins
Ascorbic Acid
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents