Safety and Efficacy of Nabilone in Alzheimer's Disease
关键词
抽象
描述
Objectives: The investigators objective is to provide pilot data addressing whether the ∆9-tetrahydrocannabinol (THC) analogue nabilone is a pharmacological option for managing agitation, a particularly difficult to treat neuropsychiatric symptom (NPS), as well as having benefits for pain, weight and overall NPS, and gather double-blind information on tolerability and safety. This group of symptoms is particularly prevalent in patients with moderate to severe AD.
Rationale: The high prevalence and impact of agitation in patients with moderate to severe Alzheimer's disease (AD) makes this neuropsychiatric symptom (NPS) a key determinant of decreased quality of life. Associated with agitation are weight loss, and pain, both of which lead to additional loss of quality of life. Agitation frequently necessitates use of antipsychotics, which, while well-studied, have modest efficacy and severe side effects including increased mortality. With the development of synthetic THC analogues, the therapeutic potential of cannabinoids can now be evaluated. Cannabinoids can be prescribed as capsules to treat anorexia and pain in certain patient groups. In addition to these potentially beneficial effects on appetite and pain, a recent study suggested positive effects of nabilone on agitation in dementia. Importantly, in addition to psychotropic effects, emerging evidence suggests neuroprotective (inhibit Aβ-induced microglial activation and excitotoxicity) and anti-inflammatory abilities, which can decrease oxidative stress, in stark contrast to the negative effects of antipsychotics. As such, this system is of high potential relevance in agitated patients with AD.
Research Plan: This will be a randomized cross-over study comparing 6 weeks of nabilone and placebo, with a 1 week placebo washout preceding each treatment phase in Long-term care (LTC) patients, and outpatients with moderate to severe AD and agitation. Study outcomes will be measured at baseline and end of treatment for each treatment phase. The primary outcome measure will be the Cohen-Mansfield Agitation Inventory (CMAI). The secondary outcomes will be the weight (kg), overall NPS (Neuropsychiatric Inventory (NPI)), NPI agitation/aggression subscale, nutrition (Mini Nutritional Assessment - Short Form (MNA-SF), body mass index (BMI), skin fold thickness), pain (The Pain Assessment In Advanced Dementia (PAINAD)), cognition (Mini-Mental State Examination (MMSE); Severe Impairment Battery (SIB)) and clinical significance (Alzheimer's Cooperative Study-Clinician Global Impression of change (ADCS-CGIC). Safety (heart rate, blood pressure, and adverse events) will also be assessed at every visit.
日期
| 最后验证: | 05/31/2020 |
| 首次提交: | 11/16/2014 |
| 提交的预估入学人数: | 01/26/2015 |
| 首次发布: | 01/29/2015 |
| 上次提交的更新: | 06/22/2020 |
| 最近更新发布: | 06/24/2020 |
| 实际学习开始日期: | 12/31/2014 |
| 预计主要完成日期: | 12/31/2017 |
| 预计完成日期: | 02/28/2019 |
状况或疾病
干预/治疗
Drug: Nabilone
Drug: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Active Comparator: Nabilone Participants randomized into the nabilone arm will be prescribed nabilone for 6 weeks. After one-week placebo washout, they will be taking placebo for an additional 6 weeks. | Drug: Nabilone Participants randomized to nabilone treatment arm, will undergo a one-week placebo washout, followed by 6 weeks of nabilone treatment (weeks 1-6). Participants will then receive a one-week placebo washout (week 7), before receiving 6 weeks of placebo treatment (weeks 8-14). |
| Placebo Comparator: Placebo Participants randomized into the placebo arm will be receiving placebo for 6 weeks. After one-week placebo washout, they will be prescribed nabilone for an additional 6 weeks. | Drug: Placebo Participants randomized to placebo arm, will undergo a one-week placebo washout, followed by 6 weeks of drug matched placebo (weeks 1-6). Participants will then receive a one-week placebo washout (week 7), before receiving 6 weeks of nabilone treatment (weeks 8-14). |
资格标准
| 有资格学习的年龄 | 55 Years 至 55 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Males or females ≥55 years of age - Diagnostic and Statistical Manual (DSM) -V criteria for Major Neurocognitive Disorder due to AD. Patients with both Major Neurocognitive Disorder due to AD and Major Vascular Neurocognitive Disorder (i.e., mixed AD and cerebrovascular disease) will also be included. - Currently in moderate-to-severe stage of dementia (Mini-Mental Status Examination (MMSE) ≤24) - Presence of clinically significant agitation (Neuropsychiatric Inventory (NPI) agitation subscale ≥3) - If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months. If the ChEI and/or memantine has been discontinued, they may enroll after 1 month. Exclusion Criteria: - Change in psychotropic medications less than 1 month prior to study randomization (e.g., concomitant antidepressants) - Contraindications to nabilone (history of hypersensitivity to any cannabinoid) - Current or past significant cardiovascular disease (e.g. uncontrolled hypertension, ischemic heart disease, arrhythmia and severe heart failure) - Presence or history of other psychiatric disorders or neurological conditions (e.g. psychotic disorders, schizophrenia, stroke, epilepsy), previous or current abuse of/dependence on marijuana |
结果
主要结果指标
1. Change in agitation; Cohen-Mansfield Agitation Inventory (CMAI) [baseline (0 weeks) to 14 weeks]
次要成果指标
1. Change in neuropsychiatric symptoms; Neuropsychiatric Inventory (NPI) [baseline (0 weeks) to 14 weeks]
2. Change in cognition; Standardized Mini-mental State Examination (sMMSE) [baseline (0 weeks) to 14 weeks]
3. Change in cognition; Severe Impairment Battery (SIB) [baseline (0 weeks) to 14 weeks]
4. Change in cognition; Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) [baseline (0 weeks) to 14 weeks]
5. Change in clinical representation; Alzheimer's Disease Cooperative Study - The Clinician Global Impression (ADCS - CGIC) [2 to 14 weeks]
其他成果措施
1. Change in pain; Pain Assessment In Advanced Dementia (PAINAD) [baseline (0 weeks) to 14 weeks]
2. Change in nutritional status; Mini Nutritional Assessment - Short Form (MNA-SF) [baseline (0 weeks) to 14 weeks]
3. Change in heart rate [baseline (0 weeks) to 14 weeks]
4. Change in levels of blood biomarkers [baseline (0 weeks) to 14 weeks]
5. Change in blood pressure [baseline (0 weeks) to 14 weeks]
