A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease
Study Details
Study Description
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 |
---|---|---|
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)
Study Design
Arms and Interventions
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- Blood Hemoglobin [12 weeks]
Measure hemoglobin function
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 18 years or older.
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Written informed consent provided by the subject before study entry.
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Confirmed sickle cell disease (SCD) as determined by hemoglobin electrophoresis or liquid chromatography.
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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).
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Weight at least 40kg
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Regular compliance with comprehensive care and previous therapy.
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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:
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Inability to give informed consent.
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Experienced severe sepsis or septic shock within the previous 12 weeks.
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Last HU dose was ingested within the previous 4 weeks.
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Currently pregnant or breast-feeding.
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Alanine Aminotransferase (ALT) ≥ 3 times the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin ≥ 1.5 mg/dl.
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Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min.
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Platelet count >800 x 109/L.
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Absolute neutrophil count <1.5 x 109/L.
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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).
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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.
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Altered mental status or recurrent seizures requiring anti-seizure medications.
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Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely.
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Concurrent diagnosis of malignancy including known Myelodysplastic syndrome, leukemia, or an abnormal karyotype.
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New York Heart Association (NYHA) class III/IV status.
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Eastern Co-operative Oncology Group (ECOG) performance status ≥3.
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Participant is on chronic transfusion therapy
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Known history of illicit drug or alcohol abuse within the past 12 months.
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Other experimental or investigational drug therapy in the past 28 days.
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Taking l-glutamine within the last 28 days
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Being positive for HIV infection
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Illinois at Chicago College of Medicine | Chicago | Illinois | United States | 60612 |
Sponsors and Collaborators
- EpiDestiny, Inc.
- National Institutes of Health (NIH)
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Robert Molokie, University of Illinois at Chicago College of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019-0631
- P01HL146372
- R44HL135896