Open Label Study for the Use of Tyrosine Kinase Inhibitors for Treatment of Cognitive Decline Due to Degenerative Dementias
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Number of patients who are discontinued due to tolerability issues related to treatment
研究概览
简要总结
The present study is designed as an open label study of patients with mild cognitive impairment or dementia to evaluate longer term tolerability and potential efficacy of tyrosine kinase inhibitors. Baseline and outcome measures in this study utilize validated tests that are appropriate for repeated measures which are not affected by practice effects. Advantages of this study include the fact that the neuropsychological testing instruments and advanced MRI imaging protocols that have been in routine clinical deployment provide for a high degree of availability and reliability for diagnosis and for monitoring change of status. Quality assurance is tightly controlled. The study population is sufficiently broad and the conditions of interest are sufficiently prevalent so that recruitment of the projected numbers of subjects is not a limiting factor.
For a Phase I trial there is a proposed 150 patient sample to determine the frequency of common side effects in the population that is being studied. Subjects will be administered the initial dose of bosutinib, with dosage progressively increased over the course of the study. The initial dose of bosutinib is 100 mg tablet, once per day. The dose will be increased as tolerated up to 300 mg per day.
All subjects will be started at 100 mg/day and the dose will be increased by 100 mg each month if the lower dose is tolerated without significant side effects. That is to say, the subject will take 100 mg/day every day for the first month, 200 mg/day every day for the second month, and 300 mg/day every day for the third month and for the remainder of the study, provided that adverse reactions do not prohibit continuation at this dosage. The investigators will be using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 to monitor, evaluate, and report adverse reactions on an ongoing basis. Stopping and dose reduction rules for reported adverse reactions have been taken from the package insert of bosutinib.
详细描述
In order for a subject to be considered for this study, the following criterion is required:
• Cognitive decline with mild cognitive impairment (Clinical Dementia Rating Stage 0.5) through moderate dementia (CDR Stages 1 and 2)
All patients, according to routine best practices will have an evaluation including neurological interview and examination to screen for reversible causes of cognitive change such as depression, substance abuse, vitamin deficiency and systemic illness. All patients will have a Beck Depression scale and blood tests for B12 and thyroid hormone. Patients will have an EKG, in particular to screen for QT prolongation which is a relative counterindication for use of tyrosine kinase inhibitor therapy.
According to the package insert for bosutinib, the investigators are proposing to use an age range and dosage route that is comparable and overlapping with routine application of this drug. In addition, the investigators are proposing dosage ranges that are substantially lower than usually recommended for treatment of leukemia.
The QDRS scale will be given to all patients; a cut off score of 1.5 has been used qualify patients with a dementia score (CDR) of 0.5 (ref 19).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cognitive decline with mild cognitive impairment (Clinical Dementia Rating Stage 0.5) through moderate dementia (CDR Stages 1 and 2)
排除标准
- •Subjects with a history of hypersensitivity to bosutinib
- •Subjects with contraindications for lumbar puncture, such as bleeding abnormalities, use of anticoagulant medications, and local skin or spine abnormalities
- •Reversible causes of cognitive impairment that explains the clinical status entirely, such as hypothyroidism, depression
- •Advanced stages of any terminal illness or any active cancer that requires chemotherapy
- •Pre-existing renal impairment
- •Pre-existing hepatic impairment
- •QT prolongation
- •Significant cytopenia
- •Cardiovascular, cerebrovascular, and peripheral vascular arterial thrombosis
- •Women who are pregnant, may become pregnant, or are breastfeeding
- •Women of child-bearing potential and male participants with female partners who are of child-bearing potential
- •Subjects unable to give informed consent or in vulnerable categories, such as prisoners
研究组 & 干预措施
Bosutinib Treatment Arm
Subjects will be administered the initial dose of bosutinib, with dosage progressively increased over the course of the study. The initial dose of bosutinib is 100 mg tablet, once per day. The dose will be increased as tolerated up to 300 mg per day. The dose will be increased by 100 mg each month if the lower dose is tolerated without significant side effects. That is to say, the subject will take 100 mg/day every day for the first month, 200 mg/day every day for the second month, and 300 mg/day every day for the third month and for the remainder of the study, provided that adverse reactions do not prohibit continuation at this dosage. Stopping and dose reduction rules for reported adverse reactions have been taken from the package insert of bosutinib. The duration of treatment is 1 year.
干预措施: bosutinib (Drug)
结局指标
主要结局
Number of patients who are discontinued due to tolerability issues related to treatment
时间窗: 1 year
Outcome goal to determine safety and tolerability of study medication
次要结局
未报告次要终点
研究者
Sheldon Jordan
Neurologist
Neurological Associates of West Los Angeles