Dronabinol for Agitation in Dementia Crossover Trial

NCT05612711 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 1I01CX002671
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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)

Conditions

Dementia Moderate; Dementia Severe; Agitation,Psychomotor; Behavioral Symptoms

Keywords

Dementia; Agitation; Behavioral and Psychological Symptoms of Dementia

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (12)

• Change in agitation, Neuropsychiatric Inventory (NPI)

  Baseline (0 weeks) to 18 weeks

• Change in caregiver distress, Neuropsychiatric Inventory - Caregiver distress score

  Baseline (0 weeks) to 18 weeks

• Clinically perceptible effect of dronabinol on agitation, modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADAS-CGIC)

  Baseline (0 weeks) to 18 weeks

• Change in cognition, standardized Mini Mental Status Examination (sMMSE)

  Baseline (0 weeks) to 18 weeks

• Change in cognition, Alzheimer's Disease Assessment Scale - Cognitive Section (ADAS-Cog)

  Baseline (0 weeks) to 18 weeks

Study Arms (2)

Dronabinol First

EXPERIMENTAL

Participants will take Dronabinol 2.5 mg capsules twice daily for 1 week, followed by dronabinol 5 mg twice daily for 6 weeks, followed by dronabinol 2.5 mg twice daily for 1 week. They will then undergo a 3-week washout period, followed by placebo capsules twice daily for 8 weeks.

Drug: Dronabinol

Placebo First

EXPERIMENTAL

Participants will take matching placebo capsules twice daily for 8 weeks, followed by a three week washout period. They will then begin taking dronabinol 2.5 mg capsules twice daily for 1 week, followed by dronabinol 5 mg twice daily for 6 weeks, followed by dronabinol 2.5 mg twice daily for 1 week.

Drug: Dronabinol

Interventions

Dronabinol DRUG

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

Also known as: Marinol

Dronabinol First; Placebo First

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ralph H. Johnson VA Medical Center: lead
• JHSPH Center for Clinical Trials: collaborator

Study Sites (1)

Ralph H. Johnson VA Health Care System

Charleston, South Carolina, 29401, United States

Location

MeSH Terms

Conditions

Psychomotor Agitation; Behavioral Symptoms; Dementia; Behavior

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Brain Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Jacobo E Mintzer, MD

  Ralph H. Johnson VA Healthcare System

  PRINCIPAL INVESTIGATOR

• Jessica E Broadway, MD

  Ralph H. Johnson VA Healthcare System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drug vs placebo filler will be "over-encapsulated" for masking.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Geriatric Psychaitrist

Model Details: 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.

Study Record Dates

• First Submitted: October 28, 2022
• First Posted: November 10, 2022
• Study Start: November 1, 2023
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)