Clinical trial NCT05612711: Dronabinol for Agitation in Dementia Crossover Trial
Official title: Single-site, Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Dronabinol for the Treatment of Agitation in Outpatient With Dementia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Dementia Moderate
Dementia Severe
Agitation,Psychomotor
Behavioral Symptoms
Keywords: Dementia
Agitation
Behavioral and Psychological Symptoms of Dementia
Lead sponsor: Ralph H. Johnson VA Medical Center
Sponsor class: FED
Collaborators: name: JHSPH Center for Clinical Trials
First posted: 2022-11-10
Enrollment: 0
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Eligible subjects will be randomization to either dronabinol or placebo (1:1 assignment ratio) for a total of 8 weeks (1 week of titration, followed by 6 weeks of treatment at target dose, followed by 1 week of taper). All subjects will then undergo a 3-week placebo washout phase, followed by the crossover intervention for 8 weeks.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to study the effects of dronabinol in US Veterans with agitation related to moderate to severe dementia. The main goals of the study are:

* To evaluate the efficacy of dronabinol for the treatment of agitation in moderate to severe dementia compared to placebo
* To evaluate the safety of dronabinol in the treatment of agitation in moderate to severe dementia compared to placebo

Fifty (50) subjects will be given either dronabinol or placebo for 8 weeks. All subjects will then undergo a "washout" phase for 3 weeks, followed by the crossover intervention (i.e. subjects who received placebo during the first phase will receive dronabinol during the second phase, and vice versa). Thus, all participants will be taking dronabinol at some point during the study. During the study, subjects will undergo evaluations for:

* Agitation
* Cognitive changes
* Physical changes (i.e. labs, ekg, physical exam)

Detailed description: The investigators will conduct a phase IIa study to evaluate the efficacy and safety of dronabinol in the treatment of agitation related to dementia in the US Veteran population.

Specific Aim 1 - To evaluate the efficacy of dronabinol (target dose 5 mg bid) for the treatment of agitation in dementia.

Hypothesis: Dronabinol improves clinically significant agitation in moderate to severe dementia. Approach: The investigators will conduct a 6-week, double-blind, placebo-controlled, crossover, exploratory study of 50 Veterans suffering from moderate to severe dementia and clinically significant agitation with the Cohen Mansfield Agitation Inventory (CMAI) total score as the main outcome measure. Impact: The potential benefit of dronabinol in agitation will be evaluated.

Specific Aim 2 - To evaluate the safety of dronabinol in the treatment of agitation in moderate to severe dementia.

Hypothesis: Dronabinol is safe for the treatment of agitation in moderate to severe dementia. Approach: Outcomes of safety monitoring are to be measured by physical examination, vital signs with weight, adverse event reports, electrocardiogram, safety labs including complete metabolic panel (CMP), complete blood count (CBC), urinalysis (UA), and treatment compliance. Impact: The potential adverse effects of the 5 mg dose of dronabinol will be evaluated.

Exploratory Aims - The investigators will also evaluate the effect of dronabinol on neuropsychiatric symptoms, caregiver distress, cognition, weight, nutritional status, pain, and inflammation.

Eligibility criteria: Inclusion Criteria:

* US Veteran who is not pregnant or unable to become pregnant
* Diagnosis of Major Neurocognitive Disorder (aka dementia) of any type
* Functional Assessment Staging Test (FAST) score of 5 or higher
* Presence of clinically significant agitation and/or irritability with an NPI subscale score greater than or equal to 4
* If treated with cholinesterase inhibitors or memantine, dosage must be stable for 3 months, or if discontinued they may enroll after 1 month
* Must be able to swallow capsules
* Must meet International Psychogeriatric Association's provisional definition of agitation in dementia.
* Must have decisional capacity to sign informed consent or have a legally authorized representative available to provide consent
* Must have an available study partner who spends at least 10 hours per week with the subject.

Exclusion Criteria:

* Psychotropic medication changes (i.e. concomitant antidepressants, antipsychotics) less than 1 month prior to study randomization
* Contraindications to dronabinol (hypersensitivity or allergy to any cannabinoid or sesame oil)
* Use of cannabinoids (including over the counter products such as "CBD" or medical cannabis) or other illicit drugs in the past 3 months
* History of psychotic symptoms due to another psychiatric illness other than dementia int he past 2 years.
* Unstable current psychiatric disorder or neurologic condition (i.e. unstable depression, bipolar disorder, epilepsy, etc.) other than agitation or psychosis due to dementia.
* Suicidal ideations in the past 3 months or attempts in the past year
* Clinically significant delusions and/or hallucinations which are considered by the PI's to be a contraindication for dronabinol use
* Taking 1 or more medications which in the judgement of the PI's can be contraindicated with the use of dronabinol
* Unstable or uncontrolled medical conditions including cardiovascular system issues (i.e. angina, cardiac arrhythmias, recurrent syncope, hypertension, etc) as judged by the PI's.

Primary outcomes:
measure: Change in agitation, Cohen Mansfield Agitation Inventory (CMAI)
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Safety and tolerability, Treatment Emergent Adverse Events
timeFrame: Baseline (0 weeks) to 18 weeks
Secondary outcomes:
measure: Change in agitation, Neuropsychiatric Inventory (NPI)
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in caregiver distress, Neuropsychiatric Inventory - Caregiver distress score
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Clinically perceptible effect of dronabinol on agitation, modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADAS-CGIC)
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in cognition, standardized Mini Mental Status Examination (sMMSE)
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in cognition, Alzheimer's Disease Assessment Scale - Cognitive Section (ADAS-Cog)
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in cognition, Severe Impairment Battery
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in nutritional status, prealbumin
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in nutritional status, weight
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in pain, Pain Assessment in Advanced AD (PAIN-AD) scale
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in blood pressure
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in heart rate
timeFrame: Baseline (0 weeks) to 18 weeks
measure: Change in QTc interval on Electrocardiogram (EKG)
timeFrame: Baseline (0 weeks) to 18 weeks
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Ralph H. Johnson VA Health Care System
state: South Carolina
Study officials:
affiliation: Ralph H. Johnson VA Healthcare System
name: Jacobo E Mintzer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ralph H. Johnson VA Healthcare System
name: Jessica E Broadway, MD
role: PRINCIPAL_INVESTIGATOR
References: