Alzheimer Disease
Conditions
Keywords
Alzheimer's Disease, Amyloid, Radiotherapy
Brief summary
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.
Interventions
RADIATIONLow dose radiotherapy
10 Gy in 5 fractions of 2 Gy on 5 consecutive days
Sponsors
Valentina Garibotto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and adverse event associated with low dose brain RT | 12 months from end of RT | Assess the number of patients who report adverse events |
| Change in brain amyloid deposits | 8-12 weeks from end of RT | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neuropsychological performances | 6 months after inclusion | 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 |
Countries
Switzerland
Outcome results
None listed