Efficacy and Safety of Delta-9-tetrahydrocannabinol (∆9-THC) in Behavioural Disturbances and Pain in Dementia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Neuropsychiatric Inventory (NPI)
研究概览
简要总结
This is a phase II, randomized, placebo-controlled, double-blind, parallel-group, multicentre study to the efficacy and safety of low dose delta-9-THC in behavioural disturbances and pain in patients with mild to severe dementia, when added to an analgesic treatment with acetaminophen.
It is hypothesized that Namisol® will lead to more behavioural disturbances than placebo, when added to an analgesic treatment with acetaminophen, and as measured by a change in Neuropsychiatric Inventory (NPI) score, after a three week treatment period.
It is expected that this will be due, primarily, to psychoactive effects of Namisol® and secondary to a reduction in pain sensation (as measured with VRS and PACSLAC-D). It is expected that a reduction in NPS will positively affect quality of life and lead to better functioning in daily living.
详细描述
There is a high prevalence of behavioural disturbances (NPS) in persons with dementia. Persistent pain complaints can be a cause of NPS. Unfortunately, there is a lack of appropriate drugs for treating both these problems. This and positive suggestions from preliminary clinical studies with THC on NPS and directly fuel the study presented here.
This will be a phase II study in which the efficacy and safety of Namisol® (a tablet with THC) on behavioural disturbances, such as agitation, aggression and motor disturbances in dementia patients will be evaluated.
Secondary study objectives are :
-
To evaluate the efficacy of Namisol® on other secondary outcome measures, such as quality of life and functioning in daily activities.
-
To evaluate safety of Namisol® as assessed with physical examination, effects on cognitive functioning and adverse event monitoring.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has possible or probable dementia, type Alzheimer, vascular or mixed type dementia, according to the criteria of NINCDS-ADRDA/NINCDS-AIREN or based on an expert panel decision.
- •Clinical Dementia Rating (CDR) score 1 to 3 (mild to severe dementia).
- •Age ≥ 40 years.
- •Clinically relevant behavioral disturbances existing at least one month prior to screening, defined as a score of ≥ 10 on the NPI, including presence of the domain agitation/aggression or motor disturbance.
- •Women should be in the postmenopausal phase.
- •Availability of an informal or formal caregiver, being in touch with the subject at least twice a week.
- •Informed consent by the subject and subject's informal caregiver.
- •If applicable: subject is willing to stop his/her own pain medication, for the duration of the study.
- •Exclusion criteria:
- •Dementia other than AD, VaD or AD/VaD
- •Major psychiatric disorder such as: major depression according to DSM IV within 6 months prior to randomization, history of psychosis or mania, current hallucinations and/or delirium, current suicidal ideation or major anxiety disorder.
- •History of, or current drug abuse.
- •Current alcohol abuse or unwillingness to use no more than 2 alcoholic consumptions daily or raised gamma-glutamine transpeptidase and alkaline phosphatase .
- •Clinical or biochemical evidence of liver disease (ALT or AST ≥ twice the upper limit of normal) or known allergy to acetaminophen.
- •Severe (and/or unstable) concomitant or intercurrent illness, such as seizure, arrhythmias requiring other drugs than a beta blocker or digoxin (except sinus arrhythmia and atrial fibrillation), unstable angina pectoris, heart failure NYHA III or IV, and severe concomitant illness that requires treatment changes.
- •Known or suspected sensitivity to cannabinoids.
- •Lactosis intolerance.
- •Frequent falling due to orthostatic hypotension.
- •Use of tricyclic antidepressants (TCA), fluoxetine and/or carbamazepine.
- •Changes in dosage of antipsychotics, benzodiazepines or cholinesterase inhibitors within 2 weeks prior to intervention.
- •Participation in any other study other than the descriptive 'Parelsnoer' study.
排除标准
- 未提供
研究组 & 干预措施
Namisol
Namisol is a tablet containing delta-9-tetrahydrocannabinol, the main cannabinoid from Cannabis sativa L. Namisol is added to a standardized treatment with acetaminophen.
干预措施: delta-9-tetrahydrocannabinol (delta-THC) (Drug)
Namisol
Namisol is a tablet containing delta-9-tetrahydrocannabinol, the main cannabinoid from Cannabis sativa L. Namisol is added to a standardized treatment with acetaminophen.
干预措施: Acetaminophen (Drug)
Placebo
The control product is placebo, consisting of a tablet with similar appearance and taste of the test product. Placebo is added to a standardized treatment with acetaminophen.
干预措施: Placebo (Drug)
Placebo
The control product is placebo, consisting of a tablet with similar appearance and taste of the test product. Placebo is added to a standardized treatment with acetaminophen.
干预措施: Acetaminophen (Drug)
结局指标
主要结局
Neuropsychiatric Inventory (NPI)
时间窗: Screening, baseline, T= 2 weeks (by telephone interview) and T=3 weeks
The NPI has been accepted as the standard measure of NPS in most clinical trials, due to high validity, good inter-rater reliability, high internal consistency and its sensitivity to drug treatment effects. In clinical practice as well as clinical research the NPI is the most commonly used instrument to assess behavioral changes. The NPI evaluates 12 behavioral domains. The frequency and severity of these behaviors is scored by the informal caregiver.
次要结局
- Pain Assessment Checklist for Seniors with Limited Ability to Communicate Dutch version (PACSLAC-D)(baseline (T = 0) and T= 3 weeks)
- Caregiver Clinical Global Impression of Change (CCGIC)(baseline (T=0), T= 2 wks (by telephone interview) and T=3 wks)
- Barthel Index(baseline (T=0) and T = 3 weeks)
- Cohen-Mansfield Agitation Inventory (CMAI)(baseline (T=0) and T= 3 weeks)
- Quality of Life-Alzheimer's Disease Scale (QoL-AD)(baseline (T=0) and T= 3 weeks)
- Paired Associates Learning test Wechsler Memory Scale Revised(PAL WMS-R)(baseline (T = 0) and T = 3 weeks)
- Safety assessments(screening, baseline (T=0), T= 3 weeks. AE and compliance during telephone calls at T= 1week, T= 2 weeks and T= 5 weeks (follow up phone call))
- Verbal Rating Scale (VRS)(screening, baseline, T= 3 weeks, follow up (T= 5 weeks) and daily in a medication diary)
研究者
Marcel Olde Rikkert
Prof. dr. Marcel Olde Rikkert
Radboud University Medical Center