Effect of Low Dose Radiotherapy on Brain Amyloidosis in the Treatment of Alzheimer's Disease

Study Overview
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Brief Summary
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Alzheimer's Disease (AD) is the most frequent neurodegenerative disease associated with dementia, with a constantly increasing prevalence associated with an aging population. Amyloid deposition is considered the first molecular event occurring in AD: as already showed in an animal model, a low-dose radiotherapy (RT) course is capable of reducing AD-associated amyloid-β plaques and improve cognitive function. This pilot study wishes to investigate in 10 patients with a diagnosis of prodromal or early probable AD and with evidence of amyloid pathology the effectiveness of a short course low dose RT radiotherapy to reduce amyloid deposits in the human brain using molecular imaging (18F-Florbetapir) to show the effectiveness of the treatment on the specific target.

Official Title
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Effect of Low Dose Radiotherapy on Brain Amyloidosis in the Treatment of Alzheimer's Disease: a Randomized Pilot Study

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Radiation: Low dose radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the clinical trial and give an informed consent Clinical diagnosis of prodromal AD, or mild or moderate AD Ability to undergo neurocognitive assessment at baseline visit, alone or accompanied by a caregiver Amyloid PET scan positivity Ability to follow the 5-days RT regiment, alone or accompanied by a caregiver Exclusion Criteria: Inclusion in another disease modifying clinical trial Previous therapeutic brain irradiation Evidence of vascular cognitive impairment on Magnetic Resonance Imaging (MRI) (Fazekas score >1 and Wahlund score >=10/30) Oncologic disease (excluding skin cancer) active or in remission from less than 5 years Evidence of substance abuse (alcohol and/or other drugs) with a dependence during the previous 12 months (DSM-IV criteria) Presence of subdural hygroma's, subdural hematomas or hydrocephalus Significant psychiatric comorbidity as assessed during the clinical evaluation by the neurologist/geriatrician in charge Active or recent (within 3 months) cerebral infection/haemorrhage Immunocompromised status Prior history of seizure Dermatological skin disease of the scalp Women who are pregnant or breast feeding or who intend to become pregnant during the course of the study; Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Randomized, monocentric, prospective pilot study, pre- and post-intervention intraindividual comparison in the treated arm comparison of changes in neuropsychological performance in the treated and observational arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Observation<br>Subjects in this arm will only be followed and not treated (observational arm) | |
| Experimental: Treatment arm<br>Subjects will receive a low dose brain radiotherapy | Radiation: Low dose radiotherapy<br>* 10 Gy in 5 fractions of 2 Gy on 5 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and adverse event associated with low dose brain RT | Assess the number of patients who report adverse events | 12 months from end of RT | 
| Change in brain amyloid deposits | Assess intra-individual change in a quantitative measure of amyloid deposits on PET imaging (Standard Uptake Value ratio) SUVR between amyloid PET scans before and after low dose brain RT | 8-12 weeks from end of RT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological performances | Neurocognitive tests (assessing verbal and non-verbal memory, attention, executive function, praxis function, visuospatial functions, and language) to evaluate changes after low dose RT, as compared with a population of 10 subjects followed up clinically | 6 months after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, Amyloid, Radiotherapy