Dronabinol for Agitation in Dementia Crossover Trial

Behavioral Symptoms Clinical Trial

Official title:

Single-site, Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Dronabinol for the Treatment of Agitation in Outpatient With Dementia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05612711
• Other study ID #: 1I01CX002671
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 2023
• Est. completion date: November 2026

Study information

• Verified date: November 2022
• Source: Ralph H. Johnson VA Medical Center
• Contact: Jacobo E Mintzer, MD
• Phone: 843-367-4260
• Email: jacobo.mintzer[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: November 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Agitation,Psychomotor
• Alzheimer Disease
• Behavioral Symptoms
• Dementia
• Dementia Moderate
• Dementia Severe
• Psychomotor Agitation

Intervention

Drug:
• Dronabinol
All participants will take both dronabinol and placebo at different points in the study in this crossover design trial.

Locations

Country	Name	City	State
United States	Ralph H. Johnson VA Health Care System	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Ralph H. Johnson VA Medical Center	JHSPH Center for Clinical Trials

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in agitation, Cohen Mansfield Agitation Inventory (CMAI)	A 29-item scale to assess 4 dimensions of agitation across a range of frequencies during the previous two weeks. Scores range from 29-203, where higher scores indicate greater agitation severity.	Baseline (0 weeks) to 18 weeks
Primary	Safety and tolerability, Treatment Emergent Adverse Events	We will compare the frequency of reported adverse events using Common Terminology Criteria for Adverse Events version 4.0	Baseline (0 weeks) to 18 weeks
Secondary	Change in agitation, Neuropsychiatric Inventory (NPI)	This scale provides a comprehensive evaluation of neuropsychiatric symptoms in the previous month across 12 domains of behavior. Total scores range from 0-144, where higher scores reflect a greater level of neuropsychiatric symptom burden.	Baseline (0 weeks) to 18 weeks
Secondary	Change in caregiver distress, Neuropsychiatric Inventory - Caregiver distress score	Caregiver distress is rated for each positive neuropsychiatric symptom domain on a scale of 0 (not distressing at all) to 5 (extremely distressing). Thus total scores range from 0-60 on for the 12 domains.	Baseline (0 weeks) to 18 weeks
Secondary	Clinically perceptible effect of dronabinol on agitation, modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADAS-CGIC)	This modified version of the Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change assesses ites specific to agitation in Alzheimer's disease to produce a global rating of change in agitation and a measure of clinical significance. Scores range from 1 to 7 where 1 = marked improvement, 4 = no change, and 7 = marked worsening)	Baseline (0 weeks) to 18 weeks
Secondary	Change in cognition, standardized Mini Mental Status Examination (sMMSE)	The standardized version of the original MMSE is a 30 point scale to measure global cognition, where lower scores indicate greater cognitive impairment.	Baseline (0 weeks) to 18 weeks
Secondary	Change in cognition, Alzheimer's Disease Assessment Scale - Cognitive Section (ADAS-Cog)	This scale includes 11 items, 8 of which are performance based and 3 are ratings of language impairment. Scores range from 0-70, where higher scores indicate greater impairment. This scale will be administered to subjects scoring greater than or equal to 12 on the sMMSE.	Baseline (0 weeks) to 18 weeks
Secondary	Change in cognition, Severe Impairment Battery	The severe impairment battery is a measure of cognition developed for the evaluation of patients whose dementia severity is such that they cannot complete conventional neuropsychological testing. It will be administered to anyone with an sMMSE score less than 12. Scores range from 0 to 133, where lower scores indicate greater impairment.	Baseline (0 weeks) to 18 weeks
Secondary	Change in nutritional status, prealbumin	Assessed by changes in prealbumin (mg/dl)	Baseline (0 weeks) to 18 weeks
Secondary	Change in nutritional status, weight	Assessed by changes in weight (kg)	Baseline (0 weeks) to 18 weeks
Secondary	Change in pain, Pain Assessment in Advanced AD (PAIN-AD) scale	The PAIN-AD scale is a 5-item rater observed scale to measure pain in patients with dementia. Scores range from 0-10, where higher scores suggest a higher level of pain.	Baseline (0 weeks) to 18 weeks
Secondary	Change in blood pressure	Blood pressure (mm Hg) will be monitored every 2 weeks	Baseline (0 weeks) to 18 weeks
Secondary	Change in heart rate	Heart rate will be monitored in beats per minute (bpm) every 2 weeks to monitor safety.	Baseline (0 weeks) to 18 weeks
Secondary	Change in QTc interval on Electrocardiogram (EKG)	EKGs will be monitored at each study visit to assess changes in QTc interval and monitor safety	Baseline (0 weeks) to 18 weeks