Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease

About the study

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

Study point of contact

Lani Krauz
[email protected]


> 18 Years


Phase 1

Study type






participation requirements

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.

participation restrictions

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

Last updated 2022-03-21