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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 : Recruiting
First Posted : August 14, 2019
Last Update Posted : April 27, 2021
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
EpiDestiny, Inc.

Tracking Information
First Submitted Date  ICMJE August 12, 2019
First Posted Date  ICMJE August 14, 2019
Last Update Posted Date April 27, 2021
Actual Study Start Date  ICMJE January 24, 2020
Estimated Primary Completion Date February 5, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2019)
Blood Hemoglobin [ Time Frame: 12 weeks ]
Measure hemoglobin function
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease
Official Title  ICMJE Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease
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).
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
1:1 Randomization
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE Drug: Nicotinamide
Oral nicotinamide (Vitamin B3) alone compared to THU Decitabine combination
Other Names:
  • Decitabine
  • Tetrahydrouridine
Study Arms  ICMJE
  • Experimental: Nicotinamide
    Oral Nicotinamide 1000 mg twice daily
    Intervention: Drug: Nicotinamide
  • Experimental: THU Decitabine
    Oral 250 mg THU and 5 mg decitabine Once per week
    Intervention: Drug: Nicotinamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 12, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 3, 2022
Estimated Primary Completion Date February 5, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lani Krauz 312-413-0242 LIgnacio@UIC.EDU
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04055818
Other Study ID Numbers  ICMJE 2019-0631
P01HL146372 ( U.S. NIH Grant/Contract )
R44HL135896 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party EpiDestiny, Inc.
Study Sponsor  ICMJE EpiDestiny, Inc.
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Robert Molokie University of Illinois at Chicago College of Medicine
PRS Account EpiDestiny, Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP