Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study

NCT ID: NCT02877277

Last Updated: 2018-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-08
• Study Completion Date: 2017-05-29

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.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vitamin C

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

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo

Oral intake of placebo tablet daily for 56 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Oral intake of placebo tablet daily for 56 days

Interventions

Vitamin C

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Oral intake of placebo tablet daily for 56 days

Intervention Type: DIETARY_SUPPLEMENT

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Van Andel Research Institute

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Kirsten Grønbæk

Professor, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kirsten Grønbæk, Professor

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

Rigshospitalet

København Ø, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 31623675 (View on PubMed)

Other Identifiers

H-16022249

Identifier Type: -

Identifier Source: org_study_id