Myelodysplastic SyndromeEVITA-PilotNCT02877277
Epigenetics, Vitamin C and Abnormal Hematopoiesis - Pilot Study
A study testing Vitamin C in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- What is being tested?
- Vitamin C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 8 Aug 2016to 29 May 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- MDS/AML patient in treatment with DNMTi
Who cannot join
- Intake of vitamin C as a dietary supplement including multivitamin
- Non-compliance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Restoring Physiological Vitamin C Levels to the Normal Range: Influence on Epigenetic Regulation in Normal and Malignant Hematopoiesis
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.
Read the 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
- Being tested
- Vitamin C, Placebo
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin CDietary supplement
Oral intake of vitamin C tablet (500 mg) daily for 56 days
PlaceboDietary supplement
Oral intake of placebo tablet daily for 56 days
| Study group | Role | What they receive |
|---|---|---|
| Vitamin C | Experimental | Oral intake of vitamin C tablet (500 mg) daily for 56 days Receives: Dietary Supplement: Vitamin C |
| Placebo | Placebo comparator | Oral intake of placebo tablet daily for 56 days Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall 5-hmC/5-mC ratio
Measured: Change from baseline to day 84
Overall lysine methylation levels
Measured: Change from baseline to day 84
5-hmC/5-mC ratio at regulatory genomic regions of genes involved in hematopoietic development
Measured: Change from baseline to day 84
Accumulation of 5-hmC/5-mC at regulatory regions of ERVs
Measured: Change from baseline to day 84
Aberrant histone methylation associated with hematopoietic development
Measured: Change from baseline to day 84
Aberrant histone methylation associated with ERVs
Measured: Change from baseline to day 84
Expression levels of ERVs
Measured: Change from baseline to day 84
Activity of the viral defense pathway measured by RNA and protein expression
Measured: Change from baseline to day 84
ERV specific T-cell recognition in vivo
Measured: Change from baseline to day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2016 (estimated)
- Study start8 Aug 2016
- Primary completion29 May 2017
- Study completion29 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Van Andel Research Institute
- Responsible party
- Principal investigator, Kirsten Grønbæk, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Kirsten Grønbæk, Professor, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02877277
- Sponsor's protocol ID
- H-16022249
- Acronym
- EVITA-Pilot
- Status last verified
- Sep 2018
- First submitted
- 9 Aug 2016
- Last updated
- 24 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 31623675
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Restoring Physiological Vitamin C Levels to the Normal Range: Influence on Epigenetic Regulation in Normal and Malignant Hematopoiesis
- ClinicalTrials.gov ID
- NCT02877277
- Acronym / sponsor ID
- EVITA-Pilot / H-16022249
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Van Andel Research Institute
- Study start
- 8 Aug 2016 (actual)
- Primary completion
- 29 May 2017 (actual)
- Study completion
- 29 May 2017 (actual)
- First posted
- 24 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin C | Experimental | Dietary Supplement: Vitamin COral intake of vitamin C tablet (500 mg) daily for 56 days |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboOral intake of placebo tablet daily for 56 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- MDS/AML patient in treatment with DNMTi
Key exclusion criteria (2 listed)
- Intake of vitamin C as a dietary supplement including multivitamin
- Non-compliance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin COral intake of vitamin C tablet (500 mg) daily for 56 days | Dietary supplement | Vitamin C |
| PlaceboOral intake of placebo tablet daily for 56 days | Dietary supplement | Placebo |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2018.
- Derived from this study: PubMed 31623675Gillberg 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kirsten Grønbæk, Professor principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin C in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall 5-hmC/5-mC ratio (time frame: Change from baseline to day 84). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02877277, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2018.