Phase I Feasibility Study of Low Dose Whole Brain Irradiation in the Treatment of Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 3
- 主要终点
- Common Terminology Toxicity Criteria (Version 5.0) - 12 Months
研究概览
简要总结
This study is designed to assess the safety and toxicity/adverse events associated with the use of low dose fractionated whole brain irradiation in those patients who have been diagnosed with probable Alzheimer's disease 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 might change the recognized progression of Alzheimer's Disease. The investigators will also collect information from the florbetaben F 18 Injection (AMYVID®) positron emission tomography (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
An initial 15 patients will be enrolled in the first treatment scheme (5 daily fractions of 2 Gy) and will be followed for 12 months after completion of treatment to assess safety and any toxicity/adverse events associated with treatment. In Arm 1 the 15 study participants will be enrolled in total at Botsford Radiation Oncology Center and William Beaumont Hospital (Royal Oak Campus). Once a total combined 15 patients are entered this Arm will be closed.
The second treatment arm will not be used until the last patient in the first dose arm has completed all follow up. At that point patients #16-30 will be enrolled in the second dose arm (10 daily fractions of 2 Gy). In Arm 2 the 15 study participants will be enrolled in total at both Botsford Hospital Radiation Oncology Center and William Beaumont Hospital (Royal Oak Campus). Once a total combined 15 patients are entered this Arm will be closed.
A total of 30 patients will be enrolled and each will be followed for 12 months to assess safety and toxicity/adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Criteria for Eligibility (All responses must be YES)
- •Inclusion Criteria:
- •Patients must meet all eligibility criteria to be included in the study:
- •Must be 55 years of age or older
- •Patient must meet NINCDS-ADRDA criteria for Alzheimer's Disease
- •Patient must be able to complete Mini-Mental Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) questionnaire Score Sheets
- •Patient has a Rosen Modified Hachinski Ischemic Score of less than or equal to 4
- •Patient has a MMSE score of between 10-20
- •Patient has estimated survival of greater than 12 months
- •Patient or legally authorized representative must be able to give consent
排除标准
- •Patients will be excluded from the study if they meet any of the following criteria:
- •The patient has a history of cancer except non-melanoma skin cancer
- •Patient is taking anti-epileptic medication.
- •Dermatological skin disease of the scalp
- •Patient taking Alzheimer medication within the last 3 months, i.e. Exelon, Aricept, Namenda, Reminyl or Ebixa.
- •Current presence of a clinically significant major psychiatric disorder (e.g. major depressive disorder, bipolar disorder, schizophrenia, etc., according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV))
- •Patient currently participating in another Clinical Trial.
- •Patient and legally authorized representative unable to give informed consent
- •Patient with history of focal neurological deficits (with the exception of vibratory peripheral neuropathy)
- •Non-Alzheimer dementia
- •Patient has previous history of central nervous system radiation
- •Patient has evidence of substance abuse (alcohol / or other drugs of dependence) during previous 12 months
- •History of subdural hygroma / subdural hematoma
- •History of cerebral infection / hemorrhage.
- •History that the patient is immunocompromised
- •History of seizure activity
- •History of hydrocephalus
结局指标
主要结局
Common Terminology Toxicity Criteria (Version 5.0) - 12 Months
时间窗: Baseline to12 months post-treatment
To assess a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 5.0) assessing skin, eyes, ears, and central nervous system at 12 months post-treatment. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE: (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points. Grade 5=5 points) and event scores added to produce a total patient score. Minimum score is zero, which represents no adverse events. Maximum score is 72. A higher score means a worse outcome. The total patient score at baseline subtracted from the total score at 12 months is reported. A positive number indicates an increase in adverse conditions, while a negative number indicates decreased adverse conditions.
Common Terminology Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 - 6 Weeks
时间窗: Baseline to 6 weeks post-treatment
To assess a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 5.0) assessing skin, eyes, ears, and central nervous system at 6 weeks post-treatment. Each condition/event will be given a score based on severity . The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each adverse event (AE): (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points. Grade 5=5 points) and event scores added to produce a total patient score. Minimum score is zero, which represents no adverse events. Maximum score is 72. A higher score means a worse outcome. The total patient score at baseline subtracted from the total score at 6 weeks is reported. A positive number indicates an increase in adverse conditions, while a negative number indicates decreased adverse conditions.
Common Terminology Toxicity Criteria (CTCAE) Version 5.0 - 3 Months
时间窗: Baseline 3 months post-treatment
To assess a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 5.0) assessing skin, eyes, ears, and central nervous system at 3 months post-treatment. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE: (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points. Grade 5=5 points) and event scores added to produce a total patient score. Minimum score is zero, which represents no adverse events. Maximum score is 72. A higher score means a worse outcome. The total patient score at baseline subtracted from the total score at 3 months is reported. A positive number indicates an increase in adverse conditions, while a negative number indicates decreased adverse conditions.
Common Terminology Toxicity Criteria (Version 5.0) - 6 Months
时间窗: 6 months post-treatment
To assess a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 5.0) assessing skin, eyes, ears, and central nervous system at 6 months post-treatment. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE: (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points. Grade 5=5 points) and event scores added to produce a total patient score. Minimum score is zero, which represents no adverse events. Maximum score is 72. A higher score means a worse outcome. The total patient score at baseline subtracted from the total score at 6 months is reported. A positive number indicates an increase in adverse conditions, while a negative number indicates decreased adverse conditions.
次要结局
- Neurocognitive Function - QUALID- 6 Weeks Change From Baseline(Baseline to 6 weeks post-treatment)
- Neurocognitive Function - QUALID- 3 Months Change From Baseline(Baseline to 3 months post-treatment)
- Neurocognitive Function - QUALID- 6 Months Change From Baseline(Baseline to 6 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Ratio (SUVr) for Frontal Region of the Brain Compared to Cerebellum(Baseline to 4 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Standard Deviation (SUV StdDev) From Normal Patients in SUVr Values for Frontal Region of the Brain(Baseline to 4 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Standard Deviation (SUV StdDev) From Normal Patients in SUVr Values for Precuneus Region of the Brain(Baseline to 4 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Standard Deviation (SUV StdDev) From Normal Patients in SUVr Values for Anterior Cingulate Gyrus Region of the Brain(Baseline to 4 months post-treatment)
- Neurocognitive Function - MMSE (Mini Mental Status Exam) 3 Months Change From Baseline(Baseline to 3 months post-treatment)
- Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 Months Change From Baseline(Baseline to 6 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change in "Positive" or "Negative" Determination(Baseline to 4 months post-treatment)
- Neurocognitive Function - ADAS-Cog - 6 Weeks Change From Baseline(Baseline to 6 weeks post-treatment)
- Neurocognitive Function - ADAS-Cog - 6 Months Change From Baseline(Baseline to 6 months post-treatment)
- Neurocognitive Function - QOL-AD - 6 Weeks Change From Baseline(Baseline to 6 weeks post-treatment)
- Neurocognitive Function - ADAS-Cog - 3 Months Change From Baseline(Baseline to 3 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Standard Deviation (SUV StdDev) From Normal Patients in SUVr Values for Posterior Cingulate Gyrus Region of Brain(Baseline to 4 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Ratio (SUVr) for Parietal Region of the Brain Compared to Cerebellum(Baseline to 4 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Ratio (SUVr) for Precuneus Region of the Brain Compared to Cerebellum(Baseline to 4 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Ratio (SUVr) for Anterior Cingulate Gyrus Region of the Brain Compared to Cerebellum(Baseline to 4 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Standard Deviation (SUV StdDev) From Normal Patients in SUVr Values for Parietal Region of the Brain(Baseline to 4 months post-treatment)
- Neurocognitive Function - QOL-AD - 6 Months Change From Baseline(Baseline to 6 months post-treatment)
- Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 Weeks Change From Baseline(Baseline to 6 weeks post-treatment)
- Neurocognitive Function - ADAS-Cog - 12 Months Change From Baseline(Baseline to 12 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Ratio (SUVr) for Posterior Cingulate Gyrus Region of the Brain Compared to Cerebellum(Baseline to 4 months post-treatment)
- Neurocognitive Function - MMSE (Mini Mental Status Exam) 12 Months Change From Baseline(Baseline to 12 months post-treatment)
- Neurocognitive Function - QOL-AD - 3 Months Change From Baseline(Baseline to 3 months post-treatment)
- Neurocognitive Function - QOL-AD - 12 Months Change From Baseline(Baseline to 12 months post-treatment)
- Neurocognitive Function - QUALID- 12 Months Change From Baseline(12 months post-treatment)
- Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change From Baseline to 4 Months in Standardized Uptake Value Ratio (SUVr) for Whole Brain Cortex Compared to Cerebellum(Baseline to 4 months post-treatment)
研究者
James Fontanesi, MD
Staff physician, Radiation Oncology
William Beaumont Hospitals