NCT04055818招募中1 期
Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Blood Hemoglobin
研究概览
简要总结
A randomized control trial in 20 subjects with sickle cell disease comparing oral THU-decitabine to nicotinamide and in combination (THU, decitabine and nicotinamide).
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 ≥
- •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
研究组 & 干预措施
Nicotinamide
Experimental
Oral Nicotinamide 1000 mg twice daily
干预措施: Nicotinamide (Drug)
THU Decitabine
Experimental
Oral 250 mg THU and 5 mg decitabine Once per week
干预措施: Nicotinamide (Drug)
结局指标
主要结局
Blood Hemoglobin
时间窗: 12 weeks
Measure hemoglobin function
次要结局
未报告次要终点
研究者
研究点 (1)
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