Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
|Eligible Ages||18 Years and Over|
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Kirsten Grønbæk, Professor|
|Principal Investigator Affiliation||Rigshospitalet, Denmark|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Countries||Denmark, United States|
The disease, disorder, syndrome, illness, or injury that is being studied.
|Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia-1, Cytopenia|
BACKGROUND Recent investigations have shown that mutations in epigenetic regulators are common, both in the apparently normal hematopoiesis of the elderly and in patients (pts) with myeloid cancers. It was long anticipated that DNA methylation was a permanent silencing mark, but with the discovery of the ten eleven translocation (TET) enzymes it became clear that active demethylation occurs. The initial steps in this process are catalyzed by TET enzymes, which are, however, frequently mutated and methylated in hematological cancers. The Jumonji enzymes, which catalyze histone demethylation, are also aberrantly regulated in hematological cancers. Vitamin C (VitC) was identified in the 1930'ies as the necessary micronutrient in the prevention of scurvy. Unlike plants and most animals, humans are unable to synthesize vitC from glucose due to lack of the required enzyme, L-gulonolactone oxidase. Therefore, vitC must be provided through the diet. Recent studies recognize vitC as an important cofactor for the Fe(II)- and 2-oxoglutarate dioxygenase family. These include the TET enzymes, which are involved in the conversion of 5-methylcytosine (5-mC) to its oxidized derivatives 5-hydroxymethylcytosine (5-hmC), 5-carboxyl cytosine (5-caC), and 5-formylcytosine (5-fC), and the Jumonji enzymes that are involved in histone demethylation. Accordingly, vitC may potentially play an important role in the regulation of DNA and histone demethylation. However, > 80 percentage of hematological cancer pts were found to be severely vitC deficient. Interestingly, analyses of 20 participants included in the investigators' recently conducted randomized, placebo-controlled pilot study (NCT02877277) show that the level of vitC in MDS and CMML pts undergoing treatment with azacitidine, is easily elevated to the normal range by oral vitC supplement (unpublished data). When pts that were already taking vitC supplements were switched to placebo, the vitC levels quickly dropped below the normal range. It has also been shown that the formation of 5-hmC and its derivatives may be compromised in healthy individuals and pts with TET mutations. However, since many of these mutations are heterozygous, and since the three TET enzymes (TET1, TET2, and TET3) may have some redundancy, restoration of vitC to physiological levels might have an impact on the level of 5-hmC/5-mC in individuals with TET mutant clonal hematopoiesis or hematological cancer. Analyses of 5-hmC/5-mC levels in peripheral blood (PB) mononuclear cells (MNCs) from the participants in the pilot study also showed a clear trend toward increased 5-hmC in the vitC arm, however, after designing the trial the investigators realized that 5-hmC/5-mC levels are better measured in hematopoietic stem cells in the bone marrow (BM) where the levels are 10-20 fold higher. Thus, the pilot study will be followed-up with a randomized placebo-controlled trial of oral vitC in individuals with low-risk myeloid malignancies; i.e., CCUS or low-risk MDS/CMML, to investigate if oral vitC can change the biology of these disease entities and ultimately prevent progression. Hypotheses: 1. The investigators and collaborators have previously shown that cancer pts are vitC deficient, and individuals with CCUS, which represents pre-MDS, might also be vitC deficient. The hypothesis is that this may lead to reduced levels of 5-hmC/5-mC in vivo in both cancer pts and individuals with CCUS. 2. Elevating serum vitC levels to the normal range in CCUS and low-risk MDS/CMML pts by oral supplementation with vitC may.
Experimental: Vitamin C
Vitamin C (ascorbic acid) 500 mg/capsule. Ingestion of 2 capsules (1000 mg) daily for 12 months.
Placebo Comparator: Placebo
Placebo capsule. Ingestion of 2 capsules daily for 12 months. Placebo will be prepared as capsules that look and taste identical to the vitamin C supplement capsules. The content of the placebo is lactose, potato starch, gelatin, magnesium stearate, and talc.
Dietary Supplement: - Vitamin C (ascorbic acid)
Monotherapy with oral vitamin C supplementation to elevate plasma vitamin C level to the upper end of the physiological range.
Other: - Placebo
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