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A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT04055818
Recruitment Status : Not yet recruiting
First Posted : August 14, 2019
Last Update Posted : September 26, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
EpiDestiny, Inc.

Brief Summary:
A randomized control trial in 20 subjects with sickle cell disease comparing oral THU-decitabine to nicotinamide and in combination (THU, decitabine and nicotinamide).

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Nicotinamide Phase 1

Detailed Description:
A randomized control trial comparing oral THU-decitabine to nicotinamide (1:1 randomization), and then comparing the effects of the combination of nicotinamide with THU-decitabine vs either treatment alone. Treatment with each agent alone is for 12 weeks followed by the combination for a further 12 weeks. Patients have the option to enter an extension phase of combination treatment for an additional 24 weeks (total of 48 weeks)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 1:1 Randomization
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease
Estimated Study Start Date : October 7, 2019
Estimated Primary Completion Date : October 7, 2020
Estimated Study Completion Date : December 10, 2020


Arm Intervention/treatment
Experimental: Nicotinamide
Oral Nicotinamide 1000 mg twice daily
Drug: Nicotinamide
Oral nicotinamide (Vitamin B3) alone compared to THU Decitabine combination
Other Names:
  • Decitabine
  • Tetrahydrouridine

Experimental: THU Decitabine
Oral 250 mg THU and 5 mg decitabine Once per week
Drug: Nicotinamide
Oral nicotinamide (Vitamin B3) alone compared to THU Decitabine combination
Other Names:
  • Decitabine
  • Tetrahydrouridine




Primary Outcome Measures :
  1. Blood Hemoglobin [ Time Frame: 12 weeks ]
    Measure hemoglobin function



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Age 18 years or older.
  • Written informed consent provided by the subject before study entry.
  • Confirmed sickle cell disease (SCD) as determined by hemoglobin electrophoresis or liquid chromatography.
  • Subject is in his/her steady state and not having any acute complication due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).
  • Weight at least 40kg
  • Regular compliance with comprehensive care and previous therapy.
  • Symptomatic SCD is defined as having one of following, despite at least 6 months of hydroxyurea therapy, or refuse to take hydroxyurea for personal reasons: fetal hemoglobin <0.5 g/dL, or 3 or more pain episodes per year requiring parenteral narcotics, or 1 or more acute chest syndrome episodes, or Hemoglobin <9 g/dL and absolute reticulocyte count <250,000/mm3.

Exclusion Criteria:

  • Inability to give informed consent.
  • Experienced severe sepsis or septic shock within the previous 12 weeks.
  • Last HU dose was ingested within the previous 4 weeks.
  • Currently pregnant or breast-feeding.
  • Alanine Aminotransferase (ALT) ≥ 3 times the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin ≥ 1.5 mg/dl.
  • Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min.
  • Platelet count >800 x 109/L.
  • Absolute neutrophil count <1.5 x 109/L.
  • Female of active childbearing potential who is unwilling to use at least one of the two following forms of birth control: (i) not having heterosexual sexual contact beginning at the screening visit and continuing until 4 weeks after the last dose of decitabine OR (ii) intrauterine device (IUD).
  • Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of THU and decitabine. This requirement applies also to males who have had a successful vasectomy.
  • Altered mental status or recurrent seizures requiring anti-seizure medications.
  • Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely.
  • Concurrent diagnosis of malignancy including known Myelodysplastic syndrome, leukemia, or an abnormal karyotype.
  • New York Heart Association (NYHA) class III/IV status.
  • Eastern Co-operative Oncology Group (ECOG) performance status ≥3.
  • Participant is on chronic transfusion therapy
  • Known history of illicit drug or alcohol abuse within the past 12 months.
  • Other experimental or investigational drug therapy in the past 28 days.
  • Taking l-glutamine within the last 28 days
  • Being positive for HIV infection

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): NCT04055818


Contacts
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Contact: Lani Krauz 312-413-0242 LIgnacio@UIC.EDU

Sponsors and Collaborators
EpiDestiny, Inc.
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Robert Molokie University of Illinois at Chicago College of Medicine

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Responsible Party: EpiDestiny, Inc.
ClinicalTrials.gov Identifier: NCT04055818     History of Changes
Other Study ID Numbers: 2019-0631
P01HL146372 ( U.S. NIH Grant/Contract )
R44HL135896 ( U.S. NIH Grant/Contract )
First Posted: August 14, 2019    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Hematologic Diseases
Genetic Diseases, Inborn
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hemoglobinopathies
Niacinamide
Niacin
Nicotinic Acids
Decitabine
Tetrahydrouridine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents
Lipid Regulating Agents
Vasodilator Agents