The Effect of Donepezil in Radiotherapy-related Cognitive Impairment: a Randomized, Double-blind, Placebo-controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 238
- 试验地点
- 1
- 主要终点
- cognitive change
研究概览
简要总结
Purpose: This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the therapeutic effects of donepezil in radiotherapy-related cognitive impairment.
Further study details as provided by Sun Yat-sen Memorial Hospital, Sun Yat-sen University / Yameitang.
Primary outcome measure: cognitive improvement, which is determined by the difference value of ADAS-cog score before and after the treatment of donepezil.
详细描述
Application of radiotherapy to patients with head and neck cancer is a mainstay treatment in contemporary oncology practice. However, patients who received radiation are vulnerable to development of cognitive impairment. There is no acknowledged and effective standard treatment for radiotherapy-related cognitive impairment. The investigators supposed that donepezil, as a cholinesterase inhibitor, would relieve radiotherapy-related cognitive impairment after head and neck cancer, and would improve the life quality for these patients and their families.
Primary objectives: This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy of donepezil on cognition in radiotherapy-related cognitive impairment.
Secondary objectives:
To evaluate the effect of donepezil on sleep disorder, mood disorder, activities of daily living, and safety in patients with radiotherapy-related cognitive impairment.
OUTLINE: This is randomized, double-blind, placebo-controlled clinical trial. Patients will be enrolled and administrated with donepezil or placebo. Donepezil will be supplied as 10 mg per pill to be taken by mouth. Placebo will be supplied as substitute of 10 mg donepezil per pill to be taken by mouth.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) Received radiation therapy due to head and neck cancer.
- •(2) Prior irradiation ≥ 1.5 years and ≤ 6 years.
- •(3) Age>/= 35 years and age</=
- •(4) Estimated life expectancy ≥ 12 months.
- •(5) Cognitive impairment ≥ 4 weeks, with MMSE total score ≤26, or MoCA total score ≤
- •(6) Routine laboratory studies: normal bilirubin, normal aspartate aminotransferase (AST or SGOT), normal alanine aminotransferase (ALT), normal creatinine, normal white-cell count; normal neutrophils count, normal platelets count; Hb >/=110 gram per millilitres; PT, APTT, INR in a normal range.
- •(7) Constant caregivers who well understand and have willingness to sign a written informed consent document.
排除标准
- •(1) evidence of tumor metastasis, recurrence, or invasion;
- •(2) evidence of very high intracranial pressure that suggests brain hernia and need surgery;
- •(3) previous treatment with donepezil or other medications for cognitive impairment;
- •(4) history of mental disorders, epilepsy, cognitive impairment before radiotherapy;
- •(5) history of stroke, or high risk of vascular dementia;
- •(6) family history of Alzheimer's disease, Pick's disease, etc.;
- •(7) history of severe head trauma;
- •(8) clinically significant active disease, e.g. New York Heart Association Grade II or greater congestive heart failure, serious and inadequately controlled cardiac arrhythmia, bradycardia, significant vascular disease, severe infection;
- •(9) history of allergy to relevant drugs;
- •(10) pregnancy, lactation, or fertility program in the following 12 months;
- •(11) participation in other experimental studies.
研究组 & 干预措施
Donepezil
Patients receive donepezil with a dosage of 5 milligram at 8 am for one week (Week 1), then 10 milligram at 8 am for 23 weeks (Week 2-24), in the absence of unacceptable toxicity or severe deterioration.
干预措施: Donepezil Hydrochloride (Drug)
Control
Patients receive placebo with a dosage of one half pill at 8 am for one week (Week 1), then one pill at 8 am for 23 weeks (Week 2-24), in the absence of unacceptable toxicity or severe deterioration.
干预措施: Placebo (Other)
结局指标
主要结局
cognitive change
时间窗: Baseline to Week 24
Cognitive change, which is determined by the difference value of ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) before and after the treatment of donepezil. The rating of ADAS-cog is made on 6-point scale rating from 0 to 5 in 12 domains.
次要结局
- global condition change(Baseline to Week 24)
- changes of activities of daily living(Baseline to Week 24)
- cognition change(Baseline to Week 24)
- psychological statement change(Baseline to Week 24)
研究者
Yamei Tang
Professor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University