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

NCT02359864 | Terminated Results DMC FDA Device

• 1 other identifier: 2016-088; 2017-471
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

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 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.

Conditions

Alzheimer's Disease

Keywords

radiation treatment

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Baseline to12 months post-treatment

Secondary Outcomes (28)

• Florbetaben F 18 Injection (AMYVID) Positron Emission Tomography (PET) Scan: Change in "Positive" or "Negative" Determination

  Baseline to 4 months post-treatment

• Neurocognitive Function - MMSE (Mini Mental Status Exam) 6 Weeks Change From Baseline

  Baseline to 6 weeks 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

• Neurocognitive Function - MMSE (Mini Mental Status Exam) 12 Months Change From Baseline

  Baseline to 12 months post-treatment

Study Arms (2)

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.

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.

Radiation: 10 daily fractions of 2 Gy

Interventions

5 daily fractions of 2 Gy RADIATION

Whole Brain Irradiation to treat Alzheimer's Disease

Cohort One

10 daily fractions of 2 Gy RADIATION

Whole Brain Irradiation to treat Alzheimer's Disease

Cohort Two

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Corewell Health East: lead

Study Sites (2)

Beaumont Health

Farmington Hills, Michigan, 48336, United States

Location

Beaumont Health

Royal Oak, Michigan, 48073, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

Limited data was collected due to low enrollment influenced by the coronavirus-19 (COVID) pandemic. Some data was missing for some patients due to COVID restrictions on research. One patient withdrew from study.

Results Point of Contact

• Title: Dr. James Fontanesi, Professor of Neurosurgery, Director of Radiation Oncology
• Organization: William Beaumont Hospital

james.fontanesi@beaumont.org

947-521-8121

Study Officials

• James Fontanesi, MD

  Corewell Health East

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff physician, Radiation Oncology

Model Details: Single group pilot study of radiation treatment. The two arms are sequential dose increase.

Study Record Dates

• First Submitted: January 30, 2015
• First Posted: February 10, 2015
• Study Start: October 1, 2019
• Primary Completion: February 3, 2021
• Study Completion: February 3, 2021
• Last Updated: January 26, 2023
• Results First Posted: January 26, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)