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

Eastern Virginia Medical School (EVMS)

Status and phase: Enrolling; Phase 2

Conditions: Alzheimer Disease; Dementia; Major Neurocognitive Disorder With Aggressive Behavior

Treatments: Drug: THC-free CBD Oil; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04436081

RI-03368

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups, including a placebo group

Hemp-based CBD oil Gelcaps

Active Comparator group

Description:

The intervention consists of 6 weeks oral administration of CBD oil Gelcaps, starting at a dosage of 15 mg twice per day with up titration to 45 mg twice per day. At any given dose, if participants develop side effects, the dosage will be reduced to the previous dose.

Treatment:

Drug: THC-free CBD Oil

Oral placebo Gelcaps

Placebo Comparator group

Description:

Participants in the control group will receive oral placebo Gelcaps that are identical in appearance to the CBD oil Gelcaps. Dosing will be identical to the intervention arm.

Treatment:

Drug: Placebo