Clinical trial NCT04436081: Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease
Official title: Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alzheimer Disease
Dementia
Major Neurocognitive Disorder With Aggressive Behavior
Keywords: Agitation
Aggression
Neuropsychiatric symptoms
CBD Oil
Cannabinoids
Caregiver burden
Sleep quality
Behavioral and Psychological Symptoms of Dementia
Neurocognitive disorders
Psychomotor agitation
Cannabidiols
Lead sponsor: Eastern Virginia Medical School
Sponsor class: OTHER
Collaborators: name: Old Dominion University
name: Ananda Hemp, Inc.
First posted: 2020-06-17
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in agitation and aggression.
timeFrame: Every two weeks for 15 weeks during study enrollment.
measure: Change in caregiver burden.
timeFrame: Three times during the 15 weeks of study enrollment.
measure: Change in the participant's quality of life.
timeFrame: Three times during the 15 weeks of study enrollment.
measure: Change in caregiver's quality of life.
timeFrame: Three times during the 15 weeks of study enrollment.
Secondary outcomes:
measure: Assessment of change in neuropsychiatric symptoms.
timeFrame: Three times during the 15 weeks of study enrollment.
measure: Assessment of change in cognitive skills.
timeFrame: Three times during the 15 weeks of study enrollment.
measure: The effect of CBD oil on sleep quantity measured by Fitbit
timeFrame: Measured on a daily basis during the 15 weeks of study enrollment.
Other outcomes:
Locations:
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
Study officials:
affiliation: Eastern Virginia Medical School
name: Hamid Okhravi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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