A Randomized Clinical Feasibility Trial Investigating Low-Dose Radiotherapy as an Immunomodulatory Therapeutic Modality for Early-Onset Alzheimer's Disease: A Pilot Investigation
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in the CERAD-Plus score
研究概览
简要总结
The goal of this randomized clinical trial is to investigate whether low-dose whole-brain radiotherapy has a potential immunomodulatory effect that may influence disease progression in patients with early-stage Alzheimer's disease (ICD-10 diagnosed).
The main question(s) it aims to answer are:
Does low-dose radiotherapy have an effect on cognitive function and disease progression in early Alzheimer's disease? Is the intervention safe and feasible in this patient population under clinical trial conditions?
If there is a comparison group: Researchers will compare patients receiving low-dose whole-brain radiotherapy to a control group receiving a sham or non-active treatment, to assess potential differences in cognitive outcomes and disease-related parameters over time.
Participants will:
Undergo baseline diagnostic assessments including neuropsychological testing, MRI, EEG, and laboratory tests Be randomly assigned to one of two study groups Receive either low-dose whole-brain radiotherapy (6 sessions over 3 weeks) or a control condition Attend follow-up visits at 6 weeks, 3 months, and 6 months including repeated cognitive testing and clinical assessments
详细描述
The HOPE study is a prospective, randomized, controlled clinical feasibility trial investigating the potential effects of low-dose whole-brain radiotherapy as a novel immunomodulatory intervention in patients with early-stage Alzheimer's disease. The study is based on emerging preclinical and early clinical evidence suggesting that neuroinflammatory processes may contribute to the pathophysiology and progression of Alzheimer's disease, and that very low-dose ionizing radiation may exert modulatory effects on microglial activation and neuroinflammation.
The study is designed as a two-arm randomized trial in which eligible participants are assigned in a 1:1 ratio to either an intervention group receiving low-dose whole-brain radiotherapy or to a control group receiving a non-active comparator condition. Randomization is performed after completion of baseline assessments.
The radiotherapy intervention consists of a very low total dose applied to the whole brain using external beam radiotherapy techniques in a standardized treatment schedule. Treatment is delivered over a short period of time in multiple fractions. Treatment planning is performed using a dedicated planning CT scan for dose calculation and treatment positioning. Radiation delivery is carried out under strict radiotherapy quality assurance procedures in accordance with institutional standards.
Participants undergo comprehensive baseline assessments prior to randomization, including neuropsychological testing, clinical evaluation, neuroimaging (MRI), electrophysiological assessment (EEG), and laboratory investigations. Additional optional diagnostic procedures may be performed if clinically indicated. These assessments are repeated at predefined follow-up time points in order to monitor changes in cognitive function, clinical status, and safety parameters over time.
The study duration for each participant is approximately seven months, including baseline evaluation, the treatment phase, and follow-up assessments. Follow-up visits are scheduled at multiple time points after completion of the intervention to evaluate both short-term and mid-term outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Participants are blinded to treatment allocation. Treating physicians and radiotherapy staff are not blinded due to the nature of the intervention.
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Alzheimer's diagnosis according to ICD-10 Ability to understand the clinical study and provide informed consent Early-onset disease Age older than 50 years Stable treatment with anti-dementia medication for at least 3 months
排除标准
- •Prodromal Alzheimer's disease Mild cognitive impairment (MCI) Severe psychiatric disorders that could interfere with participation in the study Unstable or recently changed medication therapy Other neurodegenerative diseases or severe neurological disorders Uncontrolled chronic diseases that could increase the risk of complications Previous therapeutic brain irradiation Evidence of vascular cognitive impairment on MRI (Fazekas score >1 and Wahlund score ≥10/30) Oncological disease (except skin cancer), active or in remission for less than 5 years Evidence of substance abuse (alcohol and/or other drugs) with dependence within the last 12 months (DSM-IV criteria) Active or recent (within 3 months) cerebral infection or hemorrhage Immunocompromised status History of seizures Dermatological scalp disease Women who are pregnant, breastfeeding, or planning to become pregnant during the study period Patient has a history of cancer (except non-melanoma skin cancer) Patient is taking antiepileptic medication Patient and legally authorized representative are unable to provide informed consent Patient with a history of focal neurological deficits (except vibratory peripheral neuropathy)
研究组 & 干预措施
Low-Dose Whole-Brain Radiotherapy (Intervention Arm)
Participants in this arm receive low-dose whole-brain radiotherapy delivered using external beam radiotherapy.
干预措施: Low-Dose Whole-Brain Radiotherapy (Radiation)
Control Condition (Non-active Comparator)
Participants in this arm do not receive radiotherapy.
干预措施: Control Condition (No Radiotherapy) (Other)
结局指标
主要结局
Change in the CERAD-Plus score
时间窗: Baseline, 3 months, and 6 months after randomization
The primary endpoint is the change in the CERAD-Plus score from baseline (t0) to 6 months, as well as from baseline to 3 months. This test assesses global cognitive performance, particularly with regard to memory and executive functions. Improvements at either of these time points indicate a positive effect of the intervention on cognitive performance and the course of Alzheimer's disease.
次要结局
- Change in the FWIT scores(Baseline, 6 weeks, 3 months, 6 months)
- Changes in EEG patterns(Baseline, 6 weeks, 3 months, and 6 months after randomisation)
- Toxicity of radiotherapy according to CTCAE v5(Baseline to 6 months follow up)
- Change in the MADRS and BDI-II scores(Baseline, 6 weeks, 3 months, and 6 months after randomisation)