Development and Evaluation of Computerized Olfactory Training Program (COT) for Cognitive Decline in Early Alzheimer's Disease (AD)
试验速览
- 阶段
- 2 期
- 入组人数
- 200
- 试验地点
- 3
- 主要终点
- Logical Memory II subscale (Delayed Paragraph Recall)
研究概览
简要总结
The purpose of this study is to determine whether daily treatment with this new treatment approach, called COT would be effective in protecting the memory and brain regions of people who are already showing signs of memory loss.
详细描述
Alzheimer's disease process starts in parts of the brain used for perceiving and interpreting smell many years before people begin to lose their memory and other cognitive functions. These parts of the brain are called the "olfactory regions." From these olfactory regions, Alzheimer's disease spread to involve other parts of the brain. Scientists have shown that stimulating the olfactory regions through exposure to multiple naturally occurring essential or plant oils help to reduce the brain changes of Alzheimer's disease in animals. Also, many components from these plant oils have been shown to protect nerve cells from various kinds of stress and injuries; and we say they are 'neuroprotective'. A novel home-based olfactory chemosensory stimulation program that uses a portable, programmed, device known as the Computerized Olfactory Training (COT) program, administers olfactory psychophysical tasks while patients are being stimulated repeatedly with neuroprotective olfactory stimulants, using neuroscience-guided stimulation parameters to ensure sustained activation of all primary and secondary olfactory structures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 55-95 years; female must be post-menopausal for ≥ 2 consecutive years
- •Probable mild AD according to the core clinical criteria outlined in the National Institute on Aging/Alzheimer's Association (NIA-AA) Guidelines
- •MMSE score between the range of 21 to 27; CDR score of 1.0 (mild AD); scores on Logical Memory II subscale (Delayed Recall) from the Wechsler Memory Scale-Revised (WMS) within the recommended education-adjusted ranges
- •Have either cerebrospinal fluid (CSF) Aβ42 levels that are consistent with Alzheimer's disease as measured via mass spectrometry by C2N, or document elevated amyloid burden consistent with Alzheimer's disease from positron emission tomography (PET) imaging
- •Screening MRI without evidence of infection, infarction, or other focal lesions of neurological disease; and no significant nasal disease.
- •All participants must have a study partner with normal cognitive function.
排除标准
- •Any significant neurologic disease
- •Major psychiatric disorder within the past 2 years
- •Substance use disorder within the past 2 years
- •Any unstable medical condition
- •Contraindications to MRI
- •Any Alzheimer's disease modifying therapy (DMT) in the past 6 months
- •Antipsychotics, anticholinergics, anticonvulsants, and other antidepressants, benzodiazepines, or other psychotropic medications and blood thinners, except for aspirin at a prophylactic dose or less.
研究组 & 干预措施
Computerized Olfactory Training (COT) Device with olfactory stimulants
COT device with olfactory stimulants consists of daily 40 cycles of intervention with a combination of olfactory stimulation and training tasks, lasting ~45 minutes, delivered once daily over 6 months period by the participant or their partner/caregiver.
干预措施: COT (Drug)
Sham/COT Device
This is COT device that uses compressed room air scented with phenylethylamine (rose scent) instead of olfactory stimulants and has shape pattern matching tasks instead of cognitive tasks, in order to blind users to their treatment assignment. Similar to the COT, sham COT will be used daily for 45 minutes.
干预措施: Sham (Drug)
结局指标
主要结局
Logical Memory II subscale (Delayed Paragraph Recall)
时间窗: 9 months
Measures patient's ability to recall information after a 20 to 30 minutes delay for story b from the Wechsler Memory Scale-IV (0-25). Higher scores indicate better performance. This is use for evaluation of forgetting or memory decay.
ADCS-PACC composite score
时间窗: 9 months
Combines tests that assess episodic memory, timed executive function and global cognition. Alzheimer's Disease Cooperative Study (ADCS) PACC (ADAS-PACC) is a composite score of: The Total Recall score from the Free and Cued Selective Reminding Test (FCSRT) (range from 0-48 points), The Delayed Recall score on the Logical Memory IIa subtest from the Wechsler Memory Scale (range from 0-25 points), the Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale-Revised (range from 0-93 points), and the MMSE score (range from 0-30 points). Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. Z Scores could range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.
Olfactory Psychophysical Tasks scores
时间窗: 9 months
Using Sniffin' sticks, defines patient's olfactory threshold (T), discrimination (D) and identification (I). Scores: Male and Female threshold score (1-16); Male and Female discrimination score (4-16); Identification score (male: 3-16; female: 4-16); TDI composite score (male: 9-44; female: 11-43). Higher score indicates better olfactory performance.
Changes in cortical thickness and grey matter volumes
时间窗: Baseline and 9 months
Defines as MRI imaging changes of the hippocampus and entorhinal cortex
Changes in subfield segmentations of the hippocampus and entorhinal cortex
时间窗: Baseline and 9 months
Using the Automatic Segmentation of Hippocampal subfields looking for changes in the hippocampus and entorhinal cortex
次要结局
- Changes in the scores of Neuropsychological Test Battery (NTB)(Baseline, 6 months and 9 months)
- Changes in the scores of Mini Mental State Examination (MMSE)(Baseline, 6 months and 9 months)
- Changes in the scores of CDR scale (CDR)(Baseline, 6 months and 9 months)
- Changes in the scores of Global Deterioration Scale(GDS)(Baseline, 6 months and 9 months)
- Changes in the scores of Activities of Daily Living (ADCS-ADL)(Baseline, 6 months and 9 months)
- Changes in the scores of Quality of Life scale (QOL)(Baseline, 6 months and 9 months)
- Changes in odor discrimination scores(Baseline, 9 months)
- Changes in the grey matter volumes of other structures of the primary olfactory cortex(Baseline, 9 months)
- Changes in the cortical thickness of other structures of the primary olfactory cortex(Baseline, 9 months)