Phase IIa Trial of Low Dose Radiation THerapy to Reduce Cerebral Amyloidosis in Early Alzheimer's Dementia
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Evaluate Toxicity Associated With Delivery of Low Dose Fractionated Whole Brain Irradiation in Subjects With Early Alzheimer's Dementia According to ADRDA Criteria.
研究概览
简要总结
Evaluate safety and toxicity/adverse events associated with delivery of low dose whole brain irradiation in patients with early Alzheimer's dementia according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.. As a secondary goal it will establish whether or not the intervention with low dose whole brain irradiation stabilizes or decreases cerebral amyloid deposits and whether these correlate with the recognized progression of Alzheimer's dementia. The investigators will also collect information from the FDG and Amyvid® PET Scans to determine if there is any correlation between neurocognitive/quality of life scores and changes in amyloid plaque size, number and location.
详细描述
Alzheimer's disease (AD) is currently the 7th leading cause of death in the United States with approximately 5.9 million Americans living with the progressive and debilitating condition. AD predominantly affects older individuals as 86% of AD cases are in individuals 65 years of age and older. Further, approximately $172 billion of health care spending annually can be attributed to costs associated with AD care on top of the 11 million caregivers that provide care in unpaid capacities, such as family members, friends, etc.
In 1975, a cohort of nearly 2,800 people who were 65 years of age and free of dementia provided a basis for an incident study of dementia, as well as for Alzheimer's disease. This cohort was followed for almost 29 years and its sentinel findings included a significantly higher lifetime risk for both Alzheimer's and dementia in women compared to men. The estimated lifetime risk was nearly one in five for women compared to one in ten for men. In addition to the higher lifetime risk in women, expectancy of longer life and the aging of the "baby boomers" combined with improved healthcare is expected to increase the number of Americans who will reach 85 years of age or more. It is very clear that as the age increases, so does the incidence of Alzheimer's and other forms of dementia.
Between 2010 and 2050, it is expected that there will be a 30% increase in the number of individuals greater that 85 years of age. Although the absolute number may not appear to be significant, this increase of approximately 17 million people will challenge the healthcare system because of the cost associated with dealing various acute and chronic medical conditions including AD.
While other major causes of death continue to experience decline, those from AD continues to rise. In 1991, only approximately 14,000 death certificates recorded Alzheimer's disease as an underlying cause. In 2006, it was noted that there was an increase of approximately 46% in which Alzheimer's disease was listed as the direct cause of death. This is significant when compared to the present leading cause of death, heart disease, which decreased by 11% in the same time.
From a neurophysiological standpoint, what is known about Alzheimer's disease is that there appears to be a progressive process that is associated with the deposition of β Amyloid. This appears to have a triggering mechanism, which causes the phosphorylation of a TAU protein, which then leads to development neurofibrillary tangles (NFT), which are believed to be responsible for memory loss, especially short-term and other associated problems with Alzheimer's related dementia. It also appears that there may be a selective deposition of the β Amyloid in the hippocampus and the prefrontal regions, which are the major short-term memory regions of the brain.
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
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be a native English speaker with a LAR available for consenting.
- •Able to complete neurocognitive function assessments, psychological function assessments, and QOL assessments administered at screening visit.
- •Rosen Modified Hachinski Ischemic Score less than or equal to 4
- •Estimated Survival of greater than 12 months
- •Meets the clinical definition of AD based on NINCDS-ADRDA criteria, with confirmatory F-2-DG and F-Florbetapir (Amyvid) PET scan findings
- •If on any of the following medications, must be on a stable dose for 60 days or greater: Rivastigmine, Donepezil, Memantine, Glantamine, Tacrine.
排除标准
- •Current or past history of any oncologic disease mitigating low dose whole brain RT
- •Evidence of substance abuse (Alcohol/or other drugs or dependences during previous 12 months (DSM-V criteria)
- •Clinically or radiographically significant evidence of stroke
- •Evidence of subdural hygromas or subdural hematomas
- •Active or recent (defined as within 3 months of screening) cerebral infection or hemorrhage
- •Any current conditions that may lead to the subject being in an immuno-compromised state
- •Any previous history of cranial radiation
- •History of seizure activity
- •History of Hydrocephalus
- •Evidence of active dermatological skin disease of the scalp (except Actinic Keratosis)
- •Evidence of clinically significant major depressive disorder identified in a psychological diagnostic interview according to the criteria of the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-V)
- •Evidence of psychotic disorder or psychotic episode or bipolar affective disorder identified in a psychological diagnostic interview according to the criteria of the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-V)
- •Evidence of active suicidal or homicidal ideation according to psychological diagnostic interview
- •Currently receiving other experimental treatments
- •Currently requiring full-time institutional care
结局指标
主要结局
Evaluate Toxicity Associated With Delivery of Low Dose Fractionated Whole Brain Irradiation in Subjects With Early Alzheimer's Dementia According to ADRDA Criteria.
时间窗: 48 months
Evaluate the toxicity associated with the delivery of low dose fractionated whole brain irradiation in subjects with early Alzheimer's dementia using the CTCAE toxicity grading system. The scale is 0 - 5 with 0 being no toxicity and 5 being fatal.
次要结局
- Psychological Functioning: Anxiety(Baseline to 12 months)
- Neurocognitive Function: Visuospatial Memory(Baseline to 12 months)
- Psychological Functioning: Depression(Baseline to 12 months)
- Neurocognitive Function: Verbal Learning and Memory(Baseline to 12 months)
- Neurocognitive Function: Cognitive Function(Baseline to 12 months)
- Quality of Life in Alzheimer's Disease(Baseline to 12 months)
- Cognitive and Functional Decline(Baseline to 12 months)