Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study

Acute Myeloid Leukemia Clinical Trial

— EVITA-Pilot  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02877277
• Other study ID #: H-16022249
• Status: Completed
• Phase: N/A
• Start date: August 8, 2016
• Est. completion date: May 29, 2017

Study information

• Verified date: September 2018
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 29, 2017
• Est. primary completion date: May 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• MDS/AML patient in treatment with DNMTi

Exclusion Criteria:

• Intake of vitamin C as a dietary supplement including multivitamin

• Non-compliance

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Dietary Supplement:
• Vitamin C
Oral intake of vitamin C tablet (500 mg) daily for 56 days
• Placebo
Oral intake of placebo tablet daily for 56 days

Locations

Country	Name	City	State
Denmark	Rigshospitalet	København Ø

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Van Andel Research Institute

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall 5-hmC/5-mC ratio		Change from baseline to day 84
Primary	Overall lysine methylation levels		Change from baseline to day 84
Primary	5-hmC/5-mC ratio at regulatory genomic regions of genes involved in hematopoietic development		Change from baseline to day 84
Primary	Accumulation of 5-hmC/5-mC at regulatory regions of ERVs		Change from baseline to day 84
Primary	Aberrant histone methylation associated with hematopoietic development		Change from baseline to day 84
Primary	Aberrant histone methylation associated with ERVs		Change from baseline to day 84
Primary	Expression levels of ERVs		Change from baseline to day 84
Primary	Activity of the viral defense pathway measured by RNA and protein expression		Change from baseline to day 84
Primary	ERV specific T-cell recognition in vivo		Change from baseline to day 84