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

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

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.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease
• Intervention / Treatment: Radiation: low dose whole brain radiation to treat Alzheimer disease

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: weonkyu chung, Dr.; Phone Number: 821024187393; Email: wkchung@khnmc.or.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05278
    • Recruiting
    • Kyung Hee University Hospital at Gangdong
    • Contact: weonkyu chung, Dr.; Phone Number: 821024187393; Email: wkchung@khnmc.or.kr
    • Contact: Mijoo Chung, Dr.; Email: mjwithu@khnmc.or.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 93 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
Experimental: arm1; 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; subjects 1-5 : 9Gy in 5 daily fractions subjects 6-10 : 5.4Gy in 3 daily fractions
Experimental: arm2; 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; subjects 1-5 : 9Gy in 5 daily fractions subjects 6-10 : 5.4Gy in 3 daily fractions

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kyung Hee University Hospital at Gangdong

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): July 31, 2020

Study Registration Dates

• First Submitted: November 21, 2019
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: radiotherapy
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: KHNMC 2018-09-022-003

Drug and device information, study documents

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