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
312-413-0242
[email protected]

Locations

1 United States site

Age

> 18 Years

Phase

Phase 1

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

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

Locations

  • Chicago, Illinois, United States, University of Illinois at Chicago College of Medicine, 60612 [Recruiting]
Last updated 2021-04-26