Low-Dose Radiotherapy for Alzheimer's Disease: A Phase I/II Open-Label Feasibility and Safety Study (LDRT-MIND Trial)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Safety, As Measured By Incidence of Grade 3 or Higher Treatment-Related Adverse Events
研究概览
简要总结
To evaluate the safety and tolerability of low-dose whole brain radiotherapy (WBRT) delivered as an induction course of 0.3 Gy × 10 fractions (3.0 Gy total) followed by 12 months of monthly maintenance LDRT (0.3 Gy × 10 fractions; 3.0 Gy total) in patients with Alzheimer's disease or dementia with inflammatory components
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Age ≥50 years at time of enrollment
- •Externally confirmed diagnosis by a neurologist or geriatric psychiatrist (at Renaissance Institute, collaborating neurologist Dr. Sherif Makar, MD of Charis Neurology is available for diagnostic consultation) of one of the following: a. Alzheimer's disease (per NIA-AA 2011 or 2018 criteria) b. Frontotemporal dementia with documented inflammatory features c. Dementia with Lewy bodies with elevated inflammatory CSF markers d. Other neurodegenerative dementia with confirmed inflammatory component (elevated CSF IL-6, IL-1β, or TNF-α; or neuroimaging evidence of neuroinflammation)
- •MoCA score 10-25 at baseline screening (moderate-to-mild cognitive impairment range)
- •Karnofsky Performance Status (KPS) ≥60 or ECOG Performance Status ≤2
- •Medically stable and capable of receiving radiation therapy as assessed by the treating radiation oncologist
- •Reliable caregiver or informant able to accompany the patient to ≥80% of scheduled visits
- •Written informed consent from patient (if decision-making capacity is preserved) and/or legally authorized representative (LAR); caregiver co-consent required
- •Life expectancy ≥18 months in the opinion of the treating physician
- •Ability and willingness to comply with monthly clinic visits for the 12-month maintenance period
- •--------------------------------------------------------------------------------------
排除标准
- •Prior whole brain or partial brain radiotherapy of any dose at any time
- •Active systemic malignancy requiring concurrent oncologic treatment
- •Implanted device contraindicated with radiation therapy (pacemaker, cochlear implant, deep brain stimulator, or equivalent)
- •Brain MRI demonstrating any of the following: (a) more than 4 cerebral microhemorrhages on susceptibility-weighted imaging (SWI) or gradient echo (GRE) sequences; (b) more than 1 area of superficial cortical siderosis; (c) severe white matter disease (Fazekas grade 3); or (d) any macrohemorrhage or hemosiderin-stained lesion >10 mm. These thresholds are adapted from established AD trial imaging exclusion criteria to minimize enrollment of patients with advanced cerebrovascular disease or pre-existing hemorrhagic risk factors.
- •Known active cerebral amyloid angiopathy-related inflammation (CAA-ri) or amyloid-related beta-angiitis (ABRA), whether confirmed by biopsy, CSF analysis, or neuroimaging features consistent with active leptomeningeal or parenchymal amyloid-related inflammation
- •Active autoimmune encephalitis in acute phase (patients in stable chronic phase are eligible)
- •Uncontrolled systemic infection or active sepsis at enrollment
- •Severe psychiatric comorbidity (active psychosis, active suicidal ideation) impairing protocol compliance or safety assessment
- •Concurrent enrollment in another interventional trial targeting cognitive decline or neuroinflammation
- •Pregnancy or lactation; women of childbearing potential must use adequate contraception
- •Inability to lie flat and still for radiation delivery (approximately 10-15 minutes per session)
- •MoCA <10 at baseline screening (severe dementia; insufficient cognitive range for endpoint assessment)
结局指标
主要结局
Safety, As Measured By Incidence of Grade 3 or Higher Treatment-Related Adverse Events
时间窗: From the first induction radiotherapy fraction through 30 days after the final monthly maintenance fraction (acute monitoring period), approximately 13 to 15 months
The primary endpoint is the proportion of participants who experience at least one treatment-related adverse event of Grade 3 or higher, graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events are assessed continuously and attributed to study treatment (induction plus monthly maintenance low-dose whole-brain radiotherapy) by the investigator. Feasibility is defined by an acceptable rate of Grade 3 or higher treatment-related events: 15% or lower during the Phase I lead-in (first 10 participants) and 20% or lower across the full study population (N=50). Safety is monitored continuously using a Bayesian Beta-Binomial model; the study pauses for Data Safety Monitoring Board review if the posterior probability that the true Grade 3 or higher rate exceeds 20% reaches 0.80 or greater.
次要结局
- Cognitive Preservation, As Measured By Change in Montreal Cognitive Assessment (MoCA) Score From Baseline to Month 12(Baseline to Month 12, with MoCA assessed longitudinally across the maintenance period and at a standalone Month 12 cognitive endpoint visit)
研究者
Evan Thomas
Principal Investigator
Renaissance Institute of Precision Oncology and Radiosurgery