The Safety and Scientific Validity of Low-dose Whole Brain Radiotherapy in Alzheimer's Disease.

Study Overview
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Brief Summary
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Alzheimer's disease is the most frequent neurocognitive disorder associated with dementia, with a constantly increasing prevalence associated with an aging population. Amyloid deposition is considered as the first molecular event on the onset of Alzheimer's disease. It has already been demonstrated that low-dose radiotherapy is capable of reducing Alzheimer's disease-associated amyloid-β plaques and improving cognitive function in an animal model. In human, low-dose radiotherapy has demonstrated effectiveness in reducing bronchial amyloidosis. The present study aims to conduct research by including 10 patients with a diagnosis of mild or moderately severe Alzheimer's disease and with evidence of amyloid pathology. Furthermore, the aim is to demonstrate the effectiveness of low-dose radiotherapy in reducing amyloid deposits in the human brain using molecular imaging (Flutemetamol(18F) PET) along with treatment of the specific target.

Detailed Description
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The investigators decided to use fractionated whole brain radiation doses of 1.8 Gy x 5 and 1.8 Gy x 3. Subjects will be followed with neurocognitive testing at 6 months post radiotherapy. subjects 1-5 - 9Gy in 5 daily fractions subjects 6-10 - 5.4Gy in 3 daily fractions

Official Title
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The Safety and Scientific Validity of Low-dose Whole Brain Radiotherapy on Brain Amyloidosis During the Treatment of Mild or Moderate Alzheimer's Disease.

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Radiation: low dose whole brain radiation to treat Alzheimer disease


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of mild or moderate Alzheimer's disease. Amyloid PET scan positivity. Korean Mini-Mental State Examination score ≥10 and ≤24. Clinical dementia rating scale 0.5, 1 or 2. Ability to undergo neurocognitive assessment at baseline visit, alone or accomparined by a caregiver. Ability to understand the clinical trial and give an informed consent Exclusion Criteria: previous therapeutic whole brain irradiation Evidence of seizure activity Evidence of active dermatological skin disease of the scalp. History of malignant tumors. Pregnant or breastfeeding. If the researcher determines that participation in this study is inadequate because of other findings that are considered clinically important.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: arm 1 :subjects 1-5 - 9Gy in 5 daily fractions arm 2 :subjects 6-10 - 5.4Gy in 3 daily fractions
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: arm1<br>An initial 5 patients will be enrolled in the first treatment scheme and will be followed for 6 months after completion of treatment to assess safety and any toxicity events associated with treatment. subjects 1-5 : 9 Gy in 5 fractions of 1.8 Gy on 5 consecutive days | Radiation: low dose whole brain radiation to treat Alzheimer disease<br>* subjects 1-5 : 9Gy in 5 daily fractions subjects 6-10 : 5.4Gy in 3 daily fractions<br>|
| Experimental: arm2<br>Subjects in this arm will be enrolled in the second treatment scheme and will be followed for 6 months after completion of treatment to assess safety and any toxicity events associated with treatment. subjects 6-10 : 5.4 Gy in 3 fractions of 1.8 Gy on 3 consecutive days | Radiation: low dose whole brain radiation to treat Alzheimer disease<br>* subjects 1-5 : 9Gy in 5 daily fractions subjects 6-10 : 5.4Gy in 3 daily fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate low-dose whole brain radiotherapy in subjects with early Alzheimer's dementia using neurocognitive testing methods | verification of radiation therapy effect through GDS test | 6 months after the first visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in brain amlyoid deposits | The change in SUV of the frontal, parietal, extramedullary, pre-wedge, and posterior fasciocutaneous flutemetamol (18F) PET is considered to be an effective response if the change in SUV is more than 5%. | 6 months after the first visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotherapy