Alzheimer's DiseaseNCT02359864
Study of Low Dose Whole Brain Irradiation in the Treatment of Alzheimer's Disease
A study testing 5 daily fractions of 2 Gy and 10 daily fractions of 2 Gy in people with Alzheimer's Disease, run by Corewell Health East at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- 5 daily fractions of 2 Gy and 10 daily fractions of 2 Gy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Oct 2019to 3 Feb 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Criteria for Eligibility (All responses must be YES)
- 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
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- 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
Who cannot join
- 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))
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beaumont Health
Farmington Hills, Michigan, 48336
Beaumont Health
Royal Oak, Michigan, 48073
About this study
Official title: Phase I Feasibility Study of Low Dose Whole Brain Irradiation in the Treatment of Alzheimer's Disease
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.
Read the detailed description
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.
- Conditions
- Alzheimer's Disease
- Being tested
- 5 daily fractions of 2 Gy, 10 daily fractions of 2 Gy
- Keywords
- radiation treatment
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5 daily fractions of 2 GyRadiation
Whole Brain Irradiation to treat Alzheimer's Disease
10 daily fractions of 2 GyRadiation
Whole Brain Irradiation to treat Alzheimer's Disease
| Study group | Role | What they receive |
|---|---|---|
| Cohort One | Experimental | 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. 15 patients will be enrolled and each will be followed for 12 months to assess safety and toxicity/adverse events. Receives: Radiation: 5 daily fractions of 2 Gy |
| Cohort Two | Experimental | 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). 15 patients will be enrolled and each will be followed for 12 months to assess safety and toxicity/adverse events. Receives: Radiation: 10 daily fractions of 2 Gy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Common Terminology Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 - 6 Weeks
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.
Measured: Baseline to 6 weeks post-treatment
Common Terminology Toxicity Criteria (CTCAE) Version 5.0 - 3 Months
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.
Measured: Baseline 3 months post-treatment
Common Terminology Toxicity Criteria (Version 5.0) - 6 Months
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.
Measured: 6 months post-treatment
Common Terminology Toxicity Criteria (Version 5.0) - 12 Months
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.
Measured: Baseline to12 months post-treatment
Secondary outcomes (28)
Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change in "Positive" or "Negative" Determination
The number of patients with a change in amyloid plaque burden on AMYVID PET imaging from baseline to 4 month post-treatment scans, based on an overall "positive" or "negative" determination using Eli-Lilly AMYVID criteria. A positive scan indicates moderate to frequent amyloid neuritic plaques. A negative scan indicates sparse to no neuritic plaques.
Measured: Baseline to 4 months post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 Weeks Change From Baseline
Change at 6 weeks post-treatment from the pretreatment neurocognitive evaluation utilizing the Mini Mental Status Exam (MMSE) tool; a 30-point questionnaire for assessing cognitive function. Minimum value 0, maximum value 30. Higher score means better outcome. Pretreatment total score subtracted from 6-week total score will be reported.
Measured: Baseline to 6 weeks post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 3 Months Change From Baseline
Change at 3 months post-treatment from the pretreatment neurocognitive evaluation utilizing the Mini Mental Status Exam (MMSE) tool; a 30-point questionnaire for assessing cognitive function. Minimum value 0, maximum value 30. Higher score means better outcome. Pretreatment total score subtracted from 3-month total score will be reported.
Measured: Baseline to 3 months post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 Months Change From Baseline
Change at 6 months post-treatment from the pretreatment neurocognitive evaluation utilizing the Mini Mental Status Exam (MMSE) tool; a 30-point questionnaire for assessing cognitive function. Minimum value 0, maximum value 30. Higher score means better outcome. Pretreatment total score subtracted from 6-month total score will be reported.
Measured: Baseline to 6 months post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 12 Months Change From Baseline
Change at 12 months post-treatment from the pretreatment neurocognitive evaluation utilizing the Mini Mental Status Exam (MMSE) tool; a 30-point questionnaire for assessing cognitive function. Minimum value 0, maximum value 30. Higher score means better outcome. Pretreatment total score subtracted from 12-month total score will be reported.
Measured: Baseline to 12 months post-treatment
Neurocognitive Function - ADAS-Cog - 6 Weeks Change From Baseline
Change at 6 weeks post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Disease Assessment Scale Cognitive Scales (ADAS-Cog), an 11 part questionnaire that provides a weighted score of cognitive function. Minimum score 0, maximum score 70, with higher score indicating worse outcome. Pretreatment total score subtracted from 6-week total score will be reported. Negative numbers indicate an improvement in cognition. Positive numbers indicate a worsening cognition.
Measured: Baseline to 6 weeks post-treatment
Neurocognitive Function - ADAS-Cog - 3 Months Change From Baseline
Change at 3 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Disease Assessment Scale Cognitive Scales (ADAS-Cog), an 11 part questionnaire that provides a weighted score of cognitive function. Minimum score 0, maximum score 70, with higher score indicating worse outcome. Pretreatment total score subtracted from 3-month total score will be reported. Negative numbers indicate an improvement in cognition. Positive numbers indicate a worsening cognition.
Measured: Baseline to 3 months post-treatment
Neurocognitive Function - ADAS-Cog - 6 Months Change From Baseline
Change at 6 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Disease Assessment Scale Cognitive Scales (ADAS-Cog), an 11 part questionnaire that provides a weighted score of cognitive function. Minimum score 0, maximum score 70, with higher score indicating worse outcome. Pretreatment total score subtracted from 6-month total score will be reported. Negative numbers indicate an improvement in cognition. Positive numbers indicate a worsening cognition.
Measured: Baseline to 6 months post-treatment
Neurocognitive Function - ADAS-Cog - 12 Months Change From Baseline
Change at 12 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Disease Assessment Scale Cognitive Scales (ADAS-Cog), an 11 part questionnaire that provides a weighted score of cognitive function. Minimum score 0, maximum score 70, with higher score indicating worse outcome. Pretreatment total score subtracted from 12-month total score will be reported. Negative numbers indicate an improvement in cognition. Positive numbers indicate a worsening cognition.
Measured: Baseline to 12 months post-treatment
Neurocognitive Function - QOL-AD - 6 Weeks Change From Baseline
Change at 6 weeks post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionnaire (QOL-AD) tool; a 13 item assessment with each question scored on a 4 point scale where 1=poor quality of life and 4=excellent quality of life. A cumulative score from all items will be collected (min 13 indicates poor QOL, max 52 indicates excellent QOL) and pretreatment score subtracted from 6-week score. A negative number indicates a decreased quality of life. A positive number indicates an improved quality of life
Measured: Baseline to 6 weeks post-treatment
Neurocognitive Function - QOL-AD - 3 Months Change From Baseline
Change at 3 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionaire (QOL-AD) tool; a 13 item assessment with each question scored on a 4 point scale where 1=poor quality of life and 4=excellent quality of life. A cumulative score from all items will be collected (min 13 indicates poor QOL, max 52 indicates excellent QOL) and pretreatment score subtracted from 3-month score. A negative number indicates a decreased quality of life. A positive number indicates an improved quality of life.
Measured: Baseline to 3 months post-treatment
Neurocognitive Function - QOL-AD - 6 Months Change From Baseline
Change at 6 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionaire (QOL-AD) tool; a 13 item assessment with each question scored on a 4 point scale where 1=poor quality of life and 4=excellent quality of life. A cumulative score from all items will be collected (min 13 indicates poor QOL, max 52 indicates excellent QOL) and and pretreatment score subtracted from 6-month score. A negative number indicates a decreased quality of life. A positive number indicates an improved quality of life.
Measured: Baseline to 6 months post-treatment
Neurocognitive Function - QOL-AD - 12 Months Change From Baseline
Change at 12 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionaire (QOL-AD) tool; a 13 item assessment with each question scored on a 4 point scale where 1=poor quality of life and 4=excellent quality of life. A cumulative score from all items will be collected (min 13 indicates poor QOL, max 52 indicates excellent QOL) and pretreatment score subtracted from 12-month score. A negative number indicates a decreased quality of life. A positive number indicates an improved quality of life.
Measured: Baseline to 12 months post-treatment
Neurocognitive Function - QUALID- 6 Weeks Change From Baseline
Change at 6 weeks post-treatment from the pretreatment neurocognitive evaluation utilizing The Quality of Life in Late Stage Dementia (QUALID) tool; an 11 item assessment with each question scored on a 5 point scale completed by caregiver, where 5=poor quality of life and 1=excellent quality of life. A cumulative score from all items will be collected (min 11 indicates excellent quality of life, max 55 indicates poor quality of life) and pretreatment score subtracted from 6-week score. A positive number indicates a decreased quality of life. A negative number indicates an improved quality of life.
Measured: Baseline to 6 weeks post-treatment
Neurocognitive Function - QUALID- 3 Months Change From Baseline
Change at 3 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Quality of Life in Late Stage Dementia (QUALID) tool; an 11 item assessment with each question scored on a 5 point scale completed by a patient or caregiver, where 5=poor quality of life and 1=excellent quality of life. A cumulative score from all items will be collected (min 11 indicates excellent quality of life, max 55 indicates poor quality of life) and pretreatment score subtracted from 3-month score. A positive number indicates a decreased quality of life. A negative number indicates an improved quality of life.
Measured: Baseline to 3 months post-treatment
Neurocognitive Function - QUALID- 6 Months Change From Baseline
Change at 6 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Quality of Life in Late Stage Dementia (QUALID) tool; an 11 item assessment with each question scored on a 5 point scale completed by a patient or caregiver, where 5=poor quality of life and 1=excellent quality of life. A cumulative score from all items will be collected (min 11 indicates excellent quality of life, max 55 indicates poor quality of life) and pretreatment score subtracted from 6-month score. A positive number indicates a decreased quality of life. A negative number indicates an improved quality of life.
Measured: Baseline to 6 months post-treatment
Neurocognitive Function - QUALID- 12 Months Change From Baseline
Change at 12 months post-treatment from the pretreatment neurocognitive evaluation utilizing The Quality of Life in Late Stage Dementia (QUALID) tool; an 11 item assessment with each question scored on a 5 point scale completed by a patient or caregiver, where 5=poor quality of life and 1=excellent quality of life. A cumulative score from all items will be collected (min 11 indicates excellent quality of life, max 55 indicates poor quality of life) and pretreatment score subtracted from 12-month score. A positive number indicates a decreased quality of life. A negative number indicates an improved quality of life.
Measured: 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 Frontal Region of the Brain Compared to Cerebellum
SUVr is a measure of the amount of radiotracer activity bound to beta amyloid plaque in an individual region of brain tissue compared to radiotracer activity in the cerebellum, which is rarely involved by neuritic plaques. An elevated ratio >1.10 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the frontal region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number (percentage) indicates an increase in SUVr and more plaque burden in the frontal region, while a negative number (percentage) indicates a decrease in SUVr and a reduction in plaque burden in the frontal region.
Measured: 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
SUVr is a measure of the amount of radiotracer activity bound to beta amyloid plaque in an individual region of brain tissue compared to radiotracer activity in the cerebellum, which is rarely involved by neuritic plaques. An elevated ratio >1.10 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the parietal region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number (percentage) indicates an increase in SUVr and more plaque burden in the parietal region, while a negative number (percentage) indicates a decrease in SUVr and a reduction in plaque burden in the parietal region.
Measured: 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
SUVr is a measure of the amount of radiotracer activity bound to beta amyloid plaque in an individual region of brain tissue compared to radiotracer activity in the cerebellum, which is rarely involved by neuritic plaques. An elevated ratio >1.10 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the precuneus region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number (percentage) indicates an increase in SUVr and more plaque burden in the precuneus region, while a negative number (percentage) indicates a decrease in SUVr and a reduction in plaque burden in the precuneus region.
Measured: 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
SUVr is a measure of the amount of radiotracer activity bound to beta amyloid plaque in an individual region of brain tissue compared to radiotracer activity in the cerebellum, which is rarely involved by neuritic plaques. An elevated ratio >1.10 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the anterior cingulate gyrus region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number (percentage) indicates an increase in SUVr and more plaque burden in the anterior cingulate gyrus region, while a negative number (percentage) indicates a decrease in SUVr and a reduction in plaque burden in the anterior cingulate gyrus region.
Measured: 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 Posterior Cingulate Gyrus Region of the Brain Compared to Cerebellum
SUVr is a measure of the amount of radiotracer activity bound to beta amyloid plaque in an individual region of brain tissue compared to radiotracer activity in the cerebellum, which is rarely involved by neuritic plaques. An elevated ratio >1.10 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the posterior cingulate gyrus region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number (percentage) indicates an increase in SUVr and more plaque burden in the posterior cingulate gyrus region, while a negative number (percentage) indicates a decrease in SUVr and a reduction in plaque burden in the posterior cingulate gyrus region.
Measured: 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 Whole Brain Cortex Compared to Cerebellum
SUVr is a measure of the amount of radiotracer activity bound to beta amyloid plaque in an individual region of brain tissue compared to radiotracer activity in the cerebellum, which is rarely involved by neuritic plaques. An elevated ratio >1.10 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the whole brain cortex relative to cerebellum is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number (percentage) indicates an increase in SUVr and more plaque burden in the whole brain cortex relative to cerebellum, while a negative number (percentage) indicates a decrease in SUVr and a reduction in plaque burden in the whole brain cortex relative to cerebellum.
Measured: 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
The metric SUV StdDev from normal utilizes a database of age matched, cognitively normal individuals to compare the SUV ratios for individual regions of the brain. An elevated SUV StdDev > 1.65 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the frontal region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number indicates an increase in SUV StdDev and more plaque burden in the frontal region, while a negative number indicates a decrease in SUV StdDev and a reduction in plaque burden in the frontal region
Measured: 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
The metric SUV StdDev from normal utilizes a database of age matched, cognitively normal individuals to compare the SUV ratios for individual regions of the brain. An elevated SUV StdDev > 1.65 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the parietal region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number indicates an increase in SUV StdDev and more plaque burden in the parietal region, while a negative number indicates a decrease in SUV StdDev and a reduction in plaque burden in the parietal region.
Measured: 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
The metric SUV StdDev from normal utilizes a database of age matched, cognitively normal individuals to compare the SUV ratios for individual regions of the brain. An elevated SUV StdDev > 1.65 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the precuneus region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number indicates an increase in SUV StdDev and more plaque burden in the precuneus region, while a negative number indicates a decrease in SUV StdDev and a reduction in plaque burden in the precuneus region.
Measured: 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
The metric SUV StdDev from normal utilizes a database of age matched, cognitively normal individuals to compare the SUV ratios for individual regions of the brain. An elevated SUV StdDev > 1.65 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the anterior cingulate gyrus region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number indicates an increase in SUV StdDev and more plaque burden in the anterior cingulate gyrus region, while a negative number indicates a decrease in SUV StdDev and a reduction in plaque burden in the anterior cingulate gyrus region.
Measured: 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 Posterior Cingulate Gyrus Region of Brain
The metric SUV StdDev from normal utilizes a database of age matched, cognitively normal individuals to compare the SUV ratios for individual regions of the brain. An elevated SUV StdDev > 1.65 indicates a strong likelihood of significant underlying neuritic plaque burden. The percent change from baseline to 4-month scans in the posterior cingulate gyrus region is reported (percent change is calculated by subtracting baseline value from 4-month value; the result is then divided by the baseline value and multiplied by 100 to give a percentage). A positive number indicates an increase in SUV StdDev and more plaque burden in the posterior cingulate gyrus region, while a negative number indicates a decrease in SUV StdDev and a reduction in plaque burden in the posterior cingulate gyrus region.
Measured: Baseline to 4 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study start1 Oct 2019
- Primary completion3 Feb 2021
- Study completion3 Feb 2021
Why it stopped: Staffing and budget limitations. Administrative decision to halt enrollment due to coronavirus-19 (COVID) pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Single group pilot study of radiation treatment. The two arms are sequential dose increase.
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corewell Health East
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Fontanesi, MD, Corewell Health East
- Investigators
- James Fontanesi, MD, Principal investigator, Corewell Health East
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02359864
- Sponsor's protocol ID
- 2016-088; 2017-471
- Status last verified
- Dec 2022
- First submitted
- 30 Jan 2015
- Last updated
- 26 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Feasibility Study of Low Dose Whole Brain Irradiation in the Treatment of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT02359864
- Acronym / sponsor ID
- 2016-088; 2017-471
- Conditions
- Alzheimer's Disease
- Keywords
- radiation treatment
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Staffing and budget limitations. Administrative decision to halt enrollment due to coronavirus-19 (COVID) pandemic
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Corewell Health EastUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 3 Feb 2021 (actual)
- Study completion
- 3 Feb 2021 (actual)
- First posted
- 10 Feb 2015 (estimated)
- Results
- Posted 26 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Single group pilot study of radiation treatment. The two arms are sequential dose increase.
| Arm | Type | Receives |
|---|---|---|
| Cohort One | Experimental | Radiation: 5 daily fractions of 2 GyAn 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. 15 patients will be enrolled and each will be followed for 12 months to assess safety and toxicity/adverse events. |
| Cohort Two | Experimental | Radiation: 10 daily fractions of 2 GyThe 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). 15 patients will be enrolled and each will be followed for 12 months to assess safety and toxicity/adverse events. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Criteria for Eligibility (All responses must be YES)
- 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
Key exclusion criteria (17 listed)
- 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))
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5 daily fractions of 2 GyWhole Brain Irradiation to treat Alzheimer's Disease | Radiation | Cohort One |
| 10 daily fractions of 2 GyWhole Brain Irradiation to treat Alzheimer's Disease | Radiation | Cohort Two |
Primary outcome
Common Terminology Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 - 6 Weeks
Time frame: 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
Time frame: 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
Time frame: 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.
Common Terminology Toxicity Criteria (Version 5.0) - 12 Months
Time frame: 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.
28 secondary outcomes
Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change in "Positive" or "Negative" Determination
Time frame: Baseline to 4 months post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 Weeks Change From Baseline
Time frame: Baseline to 6 weeks post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 3 Months Change From Baseline
Time frame: Baseline to 3 months post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 Months Change From Baseline
Time frame: Baseline to 6 months post-treatment
Neurocognitive Function - MMSE (Mini Mental Status Exam) 12 Months Change From Baseline
Time frame: Baseline to 12 months post-treatment
Neurocognitive Function - ADAS-Cog - 6 Weeks Change From Baseline
Time frame: Baseline to 6 weeks post-treatment
Neurocognitive Function - ADAS-Cog - 3 Months Change From Baseline
Time frame: Baseline to 3 months post-treatment
Neurocognitive Function - ADAS-Cog - 6 Months Change From Baseline
Time frame: Baseline to 6 months post-treatment
Neurocognitive Function - ADAS-Cog - 12 Months Change From Baseline
Time frame: Baseline to 12 months post-treatment
Neurocognitive Function - QOL-AD - 6 Weeks Change From Baseline
Time frame: Baseline to 6 weeks post-treatment
Neurocognitive Function - QOL-AD - 3 Months Change From Baseline
Time frame: Baseline to 3 months post-treatment
Neurocognitive Function - QOL-AD - 6 Months Change From Baseline
Time frame: Baseline to 6 months post-treatment
Neurocognitive Function - QOL-AD - 12 Months Change From Baseline
Time frame: Baseline to 12 months post-treatment
Neurocognitive Function - QUALID- 6 Weeks Change From Baseline
Time frame: Baseline to 6 weeks post-treatment
Neurocognitive Function - QUALID- 3 Months Change From Baseline
Time frame: Baseline to 3 months post-treatment
Neurocognitive Function - QUALID- 6 Months Change From Baseline
Time frame: Baseline to 6 months post-treatment
Neurocognitive Function - QUALID- 12 Months Change From Baseline
Time frame: 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 Frontal Region of the Brain Compared to Cerebellum
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Posterior Cingulate Gyrus Region of the Brain Compared to Cerebellum
Time frame: 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 Whole Brain Cortex Compared to Cerebellum
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Posterior Cingulate Gyrus Region of Brain
Time frame: Baseline to 4 months post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Fontanesi, MD principal investigator
Corewell Health East
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 5 daily fractions of 2 Gy and 10 daily fractions of 2 Gy in people with Alzheimer's Disease, run by Corewell Health East at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Common Terminology Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 - 6 Weeks (time frame: Baseline to 6 weeks post-treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023.