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Study of Low Dose Whole Brain Irradiation in the Treatment of Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT02359864
Recruitment Status : Recruiting
First Posted : February 10, 2015
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
James Fontanesi, MD, William Beaumont Hospitals

Brief 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 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 AMYVID ® (florbetaben F 18 Injection) 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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Radiation: 5 daily fractions of 2 Gy Radiation: 10 daily fractions of 2 Gy Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Single group pilot study of radiation treatment. The two arms are sequential dose increase.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Feasibility Study of Low Dose Whole Brain Irradiation in the Treatment of Alzheimer's Disease
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort One
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.
Radiation: 5 daily fractions of 2 Gy
Whole Brain Irradiation to treat Alzheimer's Disease

Experimental: Cohort Two

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.

Radiation: 10 daily fractions of 2 Gy
Whole Brain Irradiation to treat Alzheimer's Disease




Primary Outcome Measures :
  1. Common Terminology Toxicity Criteria (Version 4.0) - 6 weeks [ Time Frame: 6 weeks post treatment ]
    To assess the number of patients who experience a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 4.0) assessing skin, eyes, ears, and central nervous system at 6 weeks post treatment. Each condition/event will be given a score based on severity (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points) and event scores added to produce a total patient score.

  2. Common Terminology Toxicity Criteria (Version 4.0) - 3 months [ Time Frame: 3 months post treatment ]
    To assess the number of patients who experience a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 4.0) assessing skin, eyes, ears, and central nervous system at 3 months post treatment. Each condition/event will be given a score based on severity (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points) and event scores added to produce a total patient score.

  3. Common Terminology Toxicity Criteria (Version 4.0) - 9 months [ Time Frame: 9 months post treatment ]
    To assess the number of patients who experience a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 4.0) assessing skin, eyes, ears, and central nervous system at 9 months post treatment. Each condition/event will be given a score based on severity (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points) and event scores added to produce a total patient score.

  4. Common Terminology Toxicity Criteria (Version 4.0) - 12 months [ Time Frame: 12 months post treatment ]
    To assess the number of patients who experience a change from baseline in adverse conditions, utilizing Common Terminology Toxicity Criteria (Version 4.0) assessing skin, eyes, ears, and central nervous system at 12 months post treatment. Each condition/event will be given a score based on severity (Grade 1=1 point, Grade 2=2 points, Grade 3=3 points, Grade 4=4 points) and event scores added to produce a total patient score.


Secondary Outcome Measures :
  1. AMYVID (florbetaben F 18 Injection) PET Scan [ Time Frame: 4 months post treatment ]
    Number of patients having a change from pretreatment scan in amyloid plaque burden: number, size, and location as determined by Amyvid (florbetaben F 18 Injection) PET; scans scored as "Negative" or "Positive" by manufacturer's guidelines for display and interpretation of Amyvid images.

  2. Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 weeks change from baseline [ Time Frame: 6 weeks post treatment ]
    Change at 6 weeks post treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionaire (QOL-AD) tool; a 30-point questionnaire for assessing cognitive function. Total scores will be compared to pretreatment score.

  3. Neurocognitive Function - MMSE (Mini Mental Status Exam) 3 months change from baseline [ Time Frame: 3 months post treatment ]
    Change at 3 months post treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionaire (QOL-AD) tool; a 30-point questionnaire for assessing cognitive function. Total scores will be compared to pretreatment score.

  4. Neurocognitive Function - MMSE (Mini Mental Status Exam) 9 months change from baseline [ Time Frame: 9 months post treatment ]
    Change at 9 months post treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionaire (QOL-AD) tool; a 30-point questionnaire for assessing cognitive function. Total scores will be compared to pretreatment score.

  5. Neurocognitive Function - MMSE (Mini Mental Status Exam) 12 months change from baseline [ Time Frame: 12 months post treatment ]
    Change at 12 months post treatment from the pretreatment neurocognitive evaluation utilizing The Alzheimer's Quality of Life Questionaire (QOL-AD) tool; a 30-point questionnaire for assessing cognitive function. Total scores will be compared to pretreatment score.

  6. Neurocognitive Function - ADAS-Cog - 6 weeks change from baseline [ Time Frame: 6 weeks post treatment ]
    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. Total score will be compared to pretreatment score.

  7. Neurocognitive Function - ADAS-Cog - 3 months change from baseline [ Time Frame: 3 months post treatment ]
    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. Total score will be compared to pretreatment score.

  8. Neurocognitive Function - ADAS-Cog - 9 months change from baseline [ Time Frame: 9 months post treatment ]
    Change at 9 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. Total score will be compared to pretreatment score.

  9. Neurocognitive Function - ADAS-Cog - 12 months change from baseline [ Time Frame: 12 months post treatment ]
    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. Total score will be compared to pretreatment score.

  10. Neurocognitive Function - QOL-AD - 6 weeks change from baseline [ Time Frame: 6 weeks post treatment ]
    Change at 6 weeks 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, max 52) and compared to pretreatment score.

  11. Neurocognitive Function - QOL-AD - 3 months change from baseline [ Time Frame: 3 months post treatment ]
    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, max 52) and compared to pretreatment score.

  12. Neurocognitive Function - QOL-AD - 9 months change from baseline [ Time Frame: 9 months post treatment ]
    Change at 9 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, max 52) and compared to pretreatment score.

  13. Neurocognitive Function - QOL-AD - 12 months change from baseline [ Time Frame: 12 months post treatment ]
    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, max 52) and compared to pretreatment score.

  14. Neurocognitive Function - QUALID- 6 weeks change from baseline [ Time Frame: 6 weeks post treatment ]
    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 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, max 55) and compared to pretreatment score.

  15. Neurocognitive Function - QUALID- 3 months change from baseline [ Time Frame: 3 months post treatment ]
    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, max 55) and compared to pretreatment score.

  16. Neurocognitive Function - QUALID- 9 months change from baseline [ Time Frame: 9 months post treatment ]
    Change at 9 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, max 55) and compared to pretreatment score.

  17. Neurocognitive Function - QUALID- 12 months change from baseline [ Time Frame: 12 months post treatment ]
    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, max 55) and compared to pretreatment score.



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Criteria for Eligibility (All responses must be YES)

Inclusion Criteria:

Patients must meet all eligibility criteria to be included in the study:

  1. Must be 55 years of age or older
  2. Patient must meet NINCDS-ADRDA criteria for Alzheimer's Disease
  3. Patient must be able to complete Mini-Mental Examination (MMSE) and ADAS-Cog Score Sheets
  4. Patient has a Rosen Modified Hachinski Ischemic Score of less than or equal to 4
  5. Patient has a MMSE score of between 10-20
  6. Patient has estimated survival of greater than 12 months
  7. Patient or legally authorized representative must be able to give consent

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

  1. The patient has a history of cancer except non-melanoma skin cancer
  2. Patient is taking anti-epileptic medication.
  3. Dermatological skin disease of the scalp
  4. Patient taking Alzheimer medication, i.e. Exelon, Aricept, Namenda, Reminyl or Ebixa.
  5. 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))
  6. Patient currently participating in another Clinical Trial.
  7. Patient and legally authorized representative unable to give informed consent
  8. Patient with history of focal neurological deficits (with the exception of vibratory peripheral neuropathy)
  9. Non-Alzheimer dementia
  10. Patient has previous history of central nervous system radiation
  11. Patient has evidence of substance abuse (alcohol / or other drugs of dependence) during previous 12 months
  12. History of subdural hygroma / subdural hematoma
  13. History of cerebral infection / hemorrhage.
  14. History that the patient is immunocompromised
  15. History of seizure activity
  16. History of hydrocephalus

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02359864


Contacts
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Contact: James Fontanesi, MD 248-471-8120 James.Fontanesi@beaumont.edu
Contact: Prakash Chinnaiyan, MD 248-551-9679 Prakash.Chinnaiyan@beaumont.edu

Locations
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United States, Michigan
Beaumont Health Recruiting
Farmington Hills, Michigan, United States, 48336
Contact: James Fontanesi, MD    248-471-8120    James.Fontanesi@beaumont.edu   
Contact: Evie Russell, BSN    248-898-5388    Evelyne.Russell@beaumont.org   
Beaumont Health Recruiting
Royal Oak, Michigan, United States, 48073
Contact: Prakash Chinnaiyan, MD    248-551-9679    Prakash.Chinnaiyan@beaumont.edu   
Contact: Joanne Gondert, BSN    248-551-0439    Joanne.Gondert@beaumont.org   
Sponsors and Collaborators
William Beaumont Hospitals
Investigators
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Principal Investigator: James Fontanesi, MD William Beaumont Hospitals

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Responsible Party: James Fontanesi, MD, Staff physician, Radiation Oncology, William Beaumont Hospitals
ClinicalTrials.gov Identifier: NCT02359864     History of Changes
Other Study ID Numbers: 2016-088; 2017-471
First Posted: February 10, 2015    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by James Fontanesi, MD, William Beaumont Hospitals:
radiation treatment
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders