Efficacy and Safety of Photobiomodulation Therapy in Patients With Mild Cognitive Impairment and Mild Alzheimer's Disease, A 6-Month, Single-Center, Randomized, Double-Blind, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Mini-Mental State Examination
研究概览
简要总结
The goal of this clinical trial is to learn if photobiomodulation therapy (PBMT) can help treat mild cognitive impairment and mild Alzheimer's disease in adults aged 50 to 85 years. It will also learn about the safety of PBMT. The main questions it aims to answer are:
Does PBMT improve cognitive function in adults with mild cognitive impairment or mild Alzheimer's disease? What medical problems do participants have when using PBMT? Researchers will compare an active PBMT device to a sham (look-alike) device that delivers no active light therapy to see if PBMT improves cognitive function.
Participants will:
Use a transcranial near-infrared light therapy device (or a matching sham device) once a day for 20 minutes, 5 days a week, for 6 months Visit the clinic for cognitive, mood, sleep, and daily-function assessments at the start of the study, at Month 3, and at Month 6 Have brain MRI scans at the start of the study, at Month 3, and at Month 6
详细描述
Alzheimer's disease and its prodromal stage, mild cognitive impairment, are characterized by progressive neurodegeneration for which disease-modifying options remain limited. Photobiomodulation therapy (PBMT) delivers non-ionizing red and near-infrared light to neural tissue, where it is absorbed by cytochrome c oxidase in the mitochondrial respiratory chain. This is hypothesized to enhance ATP production, modulate reactive oxygen species and intracellular signaling, increase regional cerebral blood flow, and support neuroprotective and anti-inflammatory processes, providing the biological basis for evaluating PBMT as a non-invasive intervention in early Alzheimer's disease.
This is a single-center, prospective, randomized, double-blind, sham-controlled trial conducted at the Department of Cognitive Disorders, Beijing Tiantan Hospital, Capital Medical University. Eligible participants are randomly allocated in a 1:1 ratio to the active PBMT arm or the sham-control arm using a computer-generated randomization sequence. To preserve double blinding, the active and sham devices are identical in appearance and operation; the sham device emits visible light at a wavelength without established photobiomodulatory effect, so that neither participants nor outcome assessors can distinguish between arms. Treatment is self-administered at home according to a fixed schedule over the 6-month intervention period, with adherence monitored through device usage records and scheduled study visits.
Assessments are performed at baseline, Month 3, and Month 6 by trained raters blinded to group allocation. Beyond the clinical and neuropsychological battery, structural and functional MRI is used to examine treatment-associated changes in cortical and hippocampal volume, white matter integrity, and cerebral blood flow perfusion, supporting exploratory analysis of the candidate mechanisms above. Safety is monitored throughout via adverse-event reporting, device-related event tracking, and review of skin and nasal tolerability. Efficacy analyses compare between- and within-group change from baseline across the cognitive, neuropsychiatric, sleep, daily-function, and caregiver-burden domains, with imaging and tolerability data used to characterize the safety profile and explore possible mechanisms of action of PBMT in AD-derived MCI and mild AD.
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1、Inclusion Criteria：
- •Age 50-85 years
- •Meet the 2011 NIA-AA diagnostic criteria for "MCI due to AD" or "probable AD dementia," or meet the 2018 NIA-AA "ATN" diagnostic framework for AD；
- •0.5 ≤ CDR ≤ 2; for illiterate: MMSE ≤ 13; for primary school education: MMSE ≤ 19; for junior high school or above: MMSE ≤ 24; for MCI: ADL-20 ≤ 22; for mild AD: ADL-20 > 22；
- •Able to understand instructions and cooperate with serological tests, scale assessments, and brain MRI；
- •Have a study partner who can participate throughout the study。
排除标准
- •Inability to complete serological tests, scale assessments, or brain MRI due to severe visual/auditory impairment, severe neuropsychiatric symptoms, contraindications to MRI, etc.
- •History of other central nervous system injuries causing cognitive decline (e.g., severe traumatic brain injury, severe CNS infection, carbon monoxide poisoning, alcohol abuse, primary CNS tumors)
- •Unstable or severe heart, lung, liver, kidney, or hematopoietic diseases, poor general health
- •Short life expectancy due to major diseases (e.g., end-stage metastatic cancer cachexia)
- •Large skin lesions or scars on the scalp, or poor heat dissipation that cannot tolerate PBMT
- •Patients with photosensitivity disorders
- •Abnormal nasal structure (deviated septum or large polyps); bacterial or viral infection; nasal dryness/bleeding; nasopharyngeal carcinoma unsuitable for intranasal device insertion.
研究组 & 干预措施
Active PBMT
Use the transcranial photobiomodulation device at 810 nm once daily for 20 minutes per session, for 5 consecutive days, followed by 2 days off.
干预措施: Photobiomodulation (Device)
Sham PBMT
Use the transcranial photobiomodulation device at 660 nm once daily for 20 minutes per session, for 5 consecutive days, followed by 2 days off.
干预措施: Photobiomodulation (Device)
结局指标
主要结局
Mini-Mental State Examination
时间窗: Baseline, Month 3, Month 6
The Mini-Mental State Examination (MMSE) assesses orientation, registration, attention and calculation, recall, and language using 11 items. Total scores range from 0 to 30; lower scores indicate worse cognitive function and higher scores indicate better cognitive function.
Montreal Cognitive Assessment
时间窗: Baseline, Month 3, Month 6
The Montreal Cognitive Assessment (MoCA) assesses visuospatial and executive function, naming, attention, language, abstraction, delayed recall, and orientation. Total scores range from 0 to 30; higher scores indicate better cognitive function and lower scores indicate worse cognitive function.
Alzheimer's Disease Assessment Scale-Cognitive Subscale
时间窗: Baseline, Month 3, Month 6
The Alzheimer's Disease Assessment Scale-Cognitive Subscale, 11-item version (ADAS-Cog-11), assesses cognitive domains including memory, language, orientation, and praxis. The total score ranges from 0 to 70, with 0 indicating the least cognitive impairment and 70 indicating the most severe cognitive impairment. Higher scores indicate worse cognitive function. A decrease in score indicates improvement, whereas an increase indicates worsening.
Clinical Dementia Rating
时间窗: Baseline, Month 3, Month 6
The Clinical Dementia Rating (CDR) assesses cognition and daily functioning. The CDR Sum of Boxes (CDR-SB) ranges from 0 to 18; higher scores indicate greater impairment. The global CDR score ranges from 0 to 3: 0 = normal, 0.5 = questionable, 1 = mild, 2 = moderate, and 3 = severe; higher scores indicate worse outcomes.
Magnetic Resonance Imaging
时间窗: Baseline, Month 3, Month 6
Magnetic resonance imaging (MRI) compares differences in cortical/hippocampal atrophy, white matter degeneration, and cerebral blood flow perfusion before and after treatment.
次要结局
- Hamilton Depression Rating Scale(Baseline, Month 3, Month 6)
- Hamilton Anxiety Rating Scale(Baseline, Month 3, Month 6)
- Neuropsychiatric Inventory(Baseline, Month 3, Month 6)
- Pittsburgh Sleep Quality Index(Baseline, Month 3, Month 6)
- Activities of Daily Living Scale(Baseline, Month 3, Month 6)
- Caregiver Burden Inventory(Baseline, Month 3, Month 6)
研究者
Jun Xu
Chief Physician, Professor, Department of Cognitive Disorders
Beijing Tiantan Hospital