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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Radiation: Low dose radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas Zilli, Dr.; Phone Number: + 41 79 55 32 563; Email: thomas.zilli@hcuge.ch
• Study Contact Backup: Name: Garibotto Valentina, Dr.; Phone Number: +41 79 55 34 459; Email: valentina.garibotto@hcuge.ch

Study Locations

• Switzerland
  • Geneva 14, Switzerland, 1211
    • Recruiting
    • Geneva University Hospital
    • Contact: Thomas Zilli, Dr.; Phone Number: + 41 79 55 32 563; Email: thomas.zilli@hcuge.ch
    • Contact: Valentina Garibotto, Dr.; Phone Number: +41 79 55 34 459; Email: valentina.garibotto@hcuge.ch
    • Sub-Investigator: Giovanni Frisoni, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Thomas Zilli
• Investigators: Principal Investigator: Thomas Zilli, Dr., University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 24, 2017

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Radiotherapy; Amyloid
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Proteostasis Deficiencies; Dementia; Tauopathies; Amyloidosis; Alzheimer Disease
• Other Study ID Numbers: 2017-01715

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No