Observation of Inhalation of CXMCI-01 Essential Oil on Patients With Mild Cognitive Impairment
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Contextual Memory Test (CMT)
研究概览
简要总结
Memory declined and cognitive impairment are common complaints in neurology clinics. Before diagnosing as dementia, individuals will undergo a transition period, including mild cognitive impairment (MCI). Neuroinflammation is an important mechanism of memory problems. For patients with MCI, there are limited available medications. Currently, there is no standardized treatment in Taiwan. The purpose of this study is to explore alternative treatment with essential oil by inhalation to improve memory, sleep, mood, and quality of life for patients with MCI.
This study will include patients who are clinically diagnosed as MCI by a neurologist. This is a double-blind randomized controlled trial, which will include 100 participants with 1:1 allocation into the intervention group and control group. The experimental group will receive 100% CXMCI-01-M Essential Oil every morning and 100% CXMCI-01-N Essential Oil by inhalation every night. The control group will receive 0.1% CXMCI-01-M Essential Oil every morning and 0.1% CXMCI-01-N Essential Oil by inhalation every night. The intervention method involves inhaling for 5 minutes, followed by wearing an essential oil necklace for 60 minutes. Examinations will be conducted before intervention (first visit, V1) and 28 days later (second visit, V2). After 28 days of finishing intervention, the third visit (V3) will be conducted. The primary outcome is the Contextual Memory Test (CMT). Secondary outcomes are Montreal Cognitive Assessment (MoCA), Taiwan Odd-Even Number Sequencing Test (TOENST), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), and 36-Item Short Form Health Survey (SF-36). Serum biomarkers of amyloid, tau protein, and metabolomics will be checked, as well as urine biomarkers related to neuroinflammation, including lipid peroxidation (LPO), 8-hydroxy-2-deoxyguanosine (8-OHdG), kynurenine, picolinate, quinolinate, and kynurenate. Changes in meridian energy will also be examined by M.E.A.D. and HRV before and after the intervention. It is expected that this study will contribute to the clinical application of CXMCI-01 Essential Oil in patients with MCI and improve their memory, mood, and sleep quality.
详细描述
< Trial Description and Rationale for Intervention >
Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) are major causes of cognitive decline, with AD being the most prevalent. Dementia is characterized by cognitive impairment, memory deficits, and neuropsychiatric symptoms, leading to loss of independence and increased caregiver burden. Current pharmacological treatments can only slow disease progression, with no curative therapy available.
The pathogenesis of neurodegeneration involves multiple mechanisms, including amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Neuroinflammation, primarily mediated by microglia and astrocytes, plays a central role in neuronal damage. Dysregulated microglia contribute to synaptic dysfunction, while pro-inflammatory astrocytes promote neuronal apoptosis through the NF-κB pathway. Oxidative stress exacerbates neurodegeneration by inducing mitochondrial dysfunction and increasing reactive oxygen species (ROS), which further promote Aβ accumulation and tau pathology.
Mild cognitive impairment (MCI) represents an intermediate stage between normal cognition and dementia. Approximately 25 percent of individuals with MCI progress to dementia within two years, while others may recover cognitive function. Current interventions, including cholinesterase inhibitors, dietary supplements, and exercise, have shown inconsistent results. Given the multifactorial nature of MCI and the potential for cognitive recovery, exploring alternative neuroprotective therapies is essential.
Olfactory dysfunction is an early biomarker of neurodegeneration, as the olfactory nerve directly connects to the limbic system, which regulates memory and emotion. Aromatherapy, the therapeutic use of essential oils, has been investigated for its effects on cognitive function. Studies on cellular and animal models have demonstrated that essential oils exert neuroprotective effects through multiple mechanisms, including reducing Aβ-induced neurotoxicity, modulating microglia-mediated neuroinflammation, regulating glutamate and GABA neurotransmission, and inhibiting tau hyperphosphorylation via glycogen synthase kinase-3β (GSK3β) suppression. Essential oils also activate cAMP response element-binding protein (CREB) signaling, enhance antioxidant defense by increasing superoxide dismutase (SOD) levels, reduce pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and modulate brain-derived neurotrophic factor (BDNF) expression. Additionally, they prevent neuronal apoptosis and mitochondrial dysfunction, inhibit acetylcholinesterase (AChE) activity, and enhance synaptic plasticity and neurotransmitter balance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Outcomes Assessor)
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
- •Aged 50 years or older, presenting with memory and cognitive impairment. Diagnosed with Mild Cognitive Impairment (MCI) by a neurologist based on clinical and psychological assessment. Mini-mental state examination(MMSE) ≥ 23 and Clinical Dementia Rating (CDR) = 0.
- •Neurological consultation: Participants must undergo a neurology consultation, including medical history review, neurological examination, and olfactory function testing.
- •No essential oil use within the past month.
排除标准
- •Dementia caused by other conditions, including: Alzheimer's disease, Parkinson's disease, vascular dementia, traumatic brain injury, central nervous system infections or multiple sclerosis
- •Cognitive impairment due to brain lesions, such as: brain tumors, hydrocephalus, severe brain atrophy
- •Severe metabolic disorders potentially affecting cognitive function, including:
- •Uncontrolled hyperthyroidism or hypothyroidism
- •Uncorrected electrolyte imbalance
- •Liver dysfunction (ALT or AST > 1.5× normal upper limit)
- •Renal dysfunction (Creatinine > 1.5× normal upper limit)
- •Uncontrolled or poorly managed diabetes (Random glucose > 200 mg/dL and HbA1c > 8%)
- •Uncontrolled or poorly managed hypertension (SBP > 160 mmHg or DBP > 100 mmHg)
- •Uncorrected vitamin B12 or folate deficiency
- •Severe anemia (Hb < 8 g/dL) or acute bleeding causing Hb < 8 g/dL
- •Current severe infection (fever > 38°C, ongoing antibiotic use, or abnormal WBC count)
- •Body Mass Index (BMI) ≥ 35
- •Severe nasal or pharyngeal diseases affecting olfactory function, or history of asthma attacks in the past six months.
- •Substance or alcohol abuse within the past two years, meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria.
- •Diagnosis of psychiatric disorders within the past year, including: Major depressive disorder, schizophrenia, bipolar disorder (DSM-5 criteria),
- •Severe insomnia, defined as:
- •(1) Experiencing insomnia symptoms for more than 50% of days per month for at least three months, causing daytime fatigue.
- •(2) Use of three or more sleep-related medications (e.g., benzodiazepines or Z-drugs).
- •History of cancer under active treatment.
- •Use of anticholinergic or acetylcholinesterase inhibitor medications. 10.Concurrent use of other neuroprotective therapies, including traditional Chinese medicine or dietary supplements (except for long-term users exceeding three months).
- •11.Allergy to essential oils. 12.Inability to comply with essential oil inhalation procedures. 13.Other conditions deemed inappropriate by the principal investigator. 14.Inability to understand or comply with study procedures, or failure to sign the informed consent form.
研究组 & 干预措施
Experimental Group - 100% CXMCI-01 Essential Oil
Experimental Group - 100% CXMCI-01 Essential Oil. Used by inhalation in the morning and night.
干预措施: Experimental Group - 100% CXMCI-01 Essential Oil (Behavioral)
Control Group - 0.1% CXMCI-01 Essential Oil (placebo)
Control Group - 0.1% CXMCI-01 Essential Oil (Placebo). Used by inhalation in the morning and night.
干预措施: Control Group - 0.1% CXMCI-01 Essential Oil (placebo) (Behavioral)
结局指标
主要结局
Contextual Memory Test (CMT)
时间窗: Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).
The Contextual Memory Test (CMT) is a standardized cognitive assessment used to evaluate memory function in individuals with mild cognitive impairment (MCI). The test measures both immediate and delayed recall of visual stimuli in a structured context. At each study visit, participants will complete both immediate and delayed recall tasks. Each section is scored out of 20 points, resulting in a total raw score ranging from 0 to 40. Higher scores indicate better memory performance. This assessment provides a quantitative and repeatable measure of episodic memory, allowing for longitudinal tracking of cognitive changes throughout the study.
次要结局
- Montreal Cognitive Assessment(MoCA)(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- Taiwan Odd-Even Number Sequencing Test (TOENST)(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- Beck Depression Inventory (BDI)(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- Beck Anxiety Inventory (BAI)(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- Pittsburgh Sleep Quality Index (PSQI)(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- 36-Item Short Form Health Survey (SF-36)(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- Plasma biomarkers related to amyloid and tau pathology(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- Urinary biomarkers related to oxidative stress and neuroinflammation(Baseline (V1), Post-Intervention (Day 28) (V2))
- Meridian energy assessment using M.E.A.D device(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)
- Heart rate variability (HRV) assessment(Baseline (V1), Post-Intervention (Day 28) (V2), and Follow-up (Day 56) (V3).)