A Study Testing Whether Low-Dose Radiation Could Help the Immune System and Possibly Improve Early-Onset Alzheimer's Disease. (HOPE)

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.

All study-related procedures are conducted in accordance with applicable national radiation protection legislation, Good Clinical Practice (GCP) guidelines, and institutional ethical standards. Prior to participation, all participants receive detailed verbal and written information about the study procedures, potential risks, and the voluntary nature of participation, and written informed consent is obtained.

Safety monitoring is an integral part of the study design. Adverse events are systematically recorded, evaluated, and reported according to regulatory requirements. Particular attention is given to neurological status, general clinical condition, and any potential radiation-related effects, although the applied radiation dose is substantially below conventional therapeutic levels.

The study is conducted in a multidisciplinary setting involving collaboration between departments of radiationtherapy and Neuropsychiatry and clinical research infrastructure units. Data collection is performed using standardized case report forms and secure electronic databases, ensuring data quality, traceability, and compliance with data protection regulations.

The HOPE study aims to generate feasibility data regarding study procedures, patient tolerability, and preliminary signals of clinical and cognitive effects of low-dose radiotherapy in Alzheimer's disease. The results are intended to inform the design of future larger-scale clinical trials in this field.