Clinical trial NCT05635968: The Clinical Trial of Low Dose Irradiation for Alzheimer's Disease
Official title: The Multicenter Phase II Clinical Trial for Evaluation of Safety and Efficacy Using Low Dose Irradiation With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Keywords: radiation therapy
Low-dose whole brain irradiation
Lead sponsor: Kyung Hee University Hospital at Gangdong
Sponsor class: OTHER
Collaborators: name: Korea Hydro&Nuclear Power Radiation Health Institute
name: Chungbuk National University Hospital
name: SMG-SNU Boramae Medical Center
First posted: 2022-12-02
Enrollment: 60
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase II, multicenter, prospective, randomized controlled trial to treat patients with Alzheimer's disease (AD) using low-dose irradiation (LDIR). This study aims to evaluate the safety and efficacy of LDIR to whole brain in patients with AD and to determine the potentially applicable radiation dose.

Detailed description: Screening tests, cognitive function tests, brain MRI, and amyloid PET are performed on subjects who voluntarily consent in writing to participate in the trial to determine whether they meet the inclusion/exclusion criteria. Randomization is assigned to eligible subjects. The experimental groups are irradiated six times for 3 weeks according to the radiation dose determined for each group, and the control group is irradiated with sham radiation. The patients assigned to the experimental group receive whole brain irradiation with 6 MV energy using a linear accelerator. In the experimental group (1), 20 patients receive 4cGy x 6 times, a total of 24 cGy of irradiation. In the experimental group (2), 20 patients receive 50 cGy x 6 times, a total of 300 cGy of irradiation. All experimental groups and control group visit the hospital about 1, 6, and 12 months after irradiation to evaluate efficacy and safety.

Eligibility criteria: Inclusion Criteria:

All of the following criteria are satisfied for the subjects to be included in the study:

1. Aged between 60 and 85 years.
2. Diagnosed with probable Alzheimer's disease (AD) dementia based on the new diagnostic criteria for Alzheimer's disease outlined by the National Institute on Aging and Alzheimer's Association (NIA-AA).
3. Stably maintaining the general AD drug treatment (donepezil, galantamine, rivastigmine, or memantine) for more than 3 months.
4. Amyloid accumulation in brain confirmed by Amyloid PET.
5. Mild AD (score range of 13 to 24 on the Korean Mini-Mental State Examination (K-MMSE) or 0.5 or 1 on the Clinical Dementia Rating scale (CDR)).
6. Able to perform cognitive function tests and imaging tests.
7. Accompanied by a guardian who provides information on the subject's overall status, cognitive function, and functional changes.
8. Written informed consent was provided by the subject or the guardian to participate in this trial.

Exclusion Criteria:

Subjects who fall under any of the following criteria are excluded from the study:

1. Previous history of radiation to the brain.
2. History of seizure within the previous 10 years of the screening time.
3. Skin disease on the scalp.
4. Previous history of malignancy.
5. Pregnancy or breastfeeding.
6. Subjects with cognitive decline associated with drugs or neurological / neurodegenerative conditions, not AD (i.e., drug abuse, vitamin B12 deficiency, thyroid dysfunction, stroke or other cerebrovascular conditions, Lewy body dementia, frontotemporal dementia, and head trauma).
7. Clinically significant, unstable mental illness (i.e., uncontrolled depression, schizophrenia, and bipolar disorder) within the last 6 months.
8. Subjects whose brain MRI confirms evidence of: acute or subacute hemorrhage, prior macro hemorrhage (defined as \>1 cm in diameter, T2 sequence) or prior subarachnoid hemorrhage unless it can be documented that the finding is not due to an underlying structural or vascular abnormality, more than 4 microhemorrhages, cortical infarct (defined as \>1.5 cm in diameter, irrespective of anatomic location), \>1 lacunar infarct (defined as \>1.5 cm in diameter), superficial siderosis, and history of diffuse white matter disease as defined by a score of 3 on the age-related white matter changes scale. Any finding that, in the opinion of the investigator, might be a contributing cause of the subject's dementia, or pose a risk to the subject, or might prevent a satisfactory MRI assessment for safety monitoring are also included in the exclusion criteria.
9. Those who have other findings that are considered clinically important, and those who are judged by the researcher to be inappropriate for participation in this study.

Primary outcomes:
measure: saftey and efficacy
timeFrame: 6 months after completion of low-dose irradiation to whole brain
measure: saftey and efficacy
timeFrame: 6 months after completion of low-dose irradiation to whole brain
Secondary outcomes:
measure: Changes in cognitive function test score
timeFrame: 6 months after completion of low-dose irradiation to whole brain
measure: Changes in cognitive function test score
timeFrame: 6 months after completion of low-dose irradiation to whole brain
measure: Changes in cognitive function test score
timeFrame: 6 months after completion of low-dose irradiation to whole brain
measure: Changes in cognitive function test score
timeFrame: 6 months after completion of low-dose irradiation to whole brain
measure: Changes in the standardized uptake value ratio (SUVR)
timeFrame: 6 months after completion of low-dose irradiation to whole brain
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
Study officials:
affiliation: Kyung Hee University Hospital at Gangdong
name: Weon-Kuu Chung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: