Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease

Обзор

This is a randomized, double-blinded, placebo-controlled, crossover trial that aims to 1) determine the efficacy of THC-free cannabidiol (CBD oil) in reducing the severity of agitation among participants and 2) determine whether THC-free CBD oil can reduce the burden on caregivers and increase the participants' quality of life.

Подробное описание

Individuals with Alzheimer's and other forms of dementia often go through a period of significant behavioral and psychological symptoms of dementia (BPSD). It is estimated that up to 90% of persons with dementia (PWD) experience behavior problems at some point. BPSDs can be challenging for both unpaid family caregivers as well as paid caregivers. Family caregivers provide the bulk of care for PWD and number over 15 million. One of the most common types of BPSDs is agitation with a prevalence of up to 87%, based on a recent systematic review. Agitation can lead to impaired daily functioning, prolongation of hospitalization, reduced time to institutionalization, and is associated with higher mortality. Additionally, agitated behavior is associated with increased injury to both patients and caregivers. Based on the 2018 Alzheimer's disease drug development pipeline report almost 70% of clinical trials related to BPSD are dedicated to agitation behavior. Finding ways to address agitation is necessary to improve overall quality of life for PWD and their caregivers. Currently, there are no medications available specifically for the treatment of BPSDs. The use of benzodiazepines, antipsychotics and mood stabilizing agents are common, but the risks and side effects often outweigh any benefits.

Several small studies have investigated the use of cannabinoids in the treatment of pathology and symptomology of Alzheimer's disease (AD), as well as treatment of the agitation component of BPSD. A handful of these studies showed that the symptoms of BPSD were decreased with the use of cannabinoids. However, due to small sample sizes, study design, and short trial duration of these studies, the efficacy of these agents on BPSD cannot be confirmed. In addition, cannabinoids have demonstrated anti-oxidant and anti-inflammatory effects, and both processes have been indicated as major contributors to the neurologic effects of AD. Some evidence exists that agitation is related to this neuroinflammatory process. This study will examine the effects of cannabinoids on the behavioral and psychological symptoms of individuals with a dementia diagnosis.

Вмешательства

• Препарат THC-free CBD Oil
  Hemp-based CBD oil Gelcaps
• Препарат Placebo
  Placebo Gelcaps

Первичные конечные точки

• Change in agitation and aggression. [Срок оценки: Every two weeks for 15 weeks during study enrollment.]
• Change in caregiver burden. [Срок оценки: Three times during the 15 weeks of study enrollment.]
• Change in the participant's quality of life. [Срок оценки: Three times during the 15 weeks of study enrollment.]
• Change in caregiver's quality of life. [Срок оценки: Three times during the 15 weeks of study enrollment.]

Вторичные конечные точки (3)

• Assessment of change in neuropsychiatric symptoms. [Срок оценки: Three times during the 15 weeks of study enrollment.]
• Assessment of change in cognitive skills. [Срок оценки: Three times during the 15 weeks of study enrollment.]
• The effect of CBD oil on sleep quantity measured by Fitbit [Срок оценки: Measured on a daily basis during the 15 weeks of study enrollment.]

Критерии участия

Критерии включения

• Males/females over 50 years old.
• Have a diagnosis of dementia due to AD or mixed AD with another type of dementia.
• A Mini-Mental State Exam score (MMSE) between 4 and 28 inclusive.
• Presence of agitation with a Neuropsychiatric Inventory (NPI)-agitation/aggression subscore > 3.
• Participants and their informal caregivers must be fluent in English (includes reading, writing, and speech) and able to give informed consent.
• For patients treated with cognitive-enhancing medications (cholinesterase inhibitors (ChEI) and/or memantine), the dosage must be stable for at least 1 month (30 days). If the ChEI and/or memantine has been discontinued, patients may enroll after 15 days.
• Eligible caregivers must either live with the participant or have a minimum of 4 hours of daily contact with them.

Критерии исключения

• Diagnosis of non-AD or non-mixed dementias.
• Very mild dementia or advanced dementia (MMSE: greater than 28 or less than 4).
• NPI-agitation-aggression score < 3.
• Having a serious or unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease which might confound assessment of safety outcomes as determined by the study physician.
• Presence or history of other serious psychiatric disorders or neurological conditions (e.g. psychotic disorders, bipolar disorder or schizophrenia).
• Current abuse of/dependence on marijuana, current drug abuse, current alcohol abuse.
• Having seizure disorders.
• Pregnant or breastfeeding
• Indication of baseline delirium as determined by the Confusion Assessment Method (CAM).
• Current use of lithium.
• Inability to swallow CBD oil softgels.
• Changes in dosage of anti-depressives within 4 weeks before randomization and during the study.
• Changes in dosage of antipsychotics or benzodiazepines within 1 week prior to randomization and during the study.
• Contraindications to CBD oil (history of hypersensitivity to any cannabinoid).
• Frequent falling due to orthostatic hypotension.
• Use of tricyclic antidepressants (TCA), fluoxetine, and/or carbamazepine. -Patients who reside in nursing homes.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Eastern Virginia Medical School — Norfolk

Публикации

• Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. Behavioral and psychological symptoms of dementia. Front Neurol. 2012 May 7;3:73. doi: 10.3389/fneur.2012.00073. eCollection 2012. PMID 22586419
• van der Linde RM, Dening T, Stephan BC, Prina AM, Evans E, Brayne C. Longitudinal course of behavioural and psychological symptoms of dementia: systematic review. Br J Psychiatry. 2016 Nov;209(5):366-377. doi: 10.1192/bjp.bp.114.148403. Epub 2016 Aug 4. PMID 27491532
• Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ. 2015 Mar 2;350:h369. doi: 10.1136/bmj.h369. PMID 25731881
• Okura T, Langa KM. Caregiver burden and neuropsychiatric symptoms in older adults with cognitive impairment: the Aging, Demographics, and Memory Study (ADAMS). Alzheimer Dis Assoc Disord. 2011 Apr-Jun;25(2):116-21. doi: 10.1097/WAD.0b013e318203f208. PMID 21192239
• Yaffe K, Fox P, Newcomer R, Sands L, Lindquist K, Dane K, Covinsky KE. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA. 2002 Apr 24;287(16):2090-7. doi: 10.1001/jama.287.16.2090. PMID 11966383
• Khan SS, Ye B, Taati B, Mihailidis A. Detecting agitation and aggression in people with dementia using sensors-A systematic review. Alzheimers Dement. 2018 Jun;14(6):824-832. doi: 10.1016/j.jalz.2018.02.004. Epub 2018 Mar 20. PMID 29571749
• Cummings J, Lee G, Ritter A, Zhong K. Alzheimer's disease drug development pipeline: 2018. Alzheimers Dement (N Y). 2018 May 3;4:195-214. doi: 10.1016/j.trci.2018.03.009. eCollection 2018. PMID 29955663
• Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994 Dec;44(12):2308-14. doi: 10.1212/wnl.44.12.2308. PMID 7991117

Идентификаторы

NCT: NCT04436081 · RI-03368

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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