Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer's Disease

NCT02792257 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00052955R01AG050515
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 5

Brief Summary

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging. Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course. One of the most troubling of these symptoms is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. There is a great need for better interventions that target Agit-AD, a major source of patient disability as well as caregiver burden and stress, particularly in the case of moderate to severe agitation. This pilot trial could open the door to "re-purposing" Dronabinol (Marinol®) as a novel and safe treatment for Agit-AD with significant public health impact.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's; Dementia; Cannabinoids; Agitation; Neuropsychiatric Symptoms

Outcome Measures

Primary Outcomes (2)

• Symptoms of Agitation as Measured by the Pittsburgh Agitation Scale

  The Pittsburgh Agitation Scale (PAS) is a tool used to assess the severity of agitation in patients, particularly with dementia. The minimum score is 0 and the maximum score is 16. A higher number means a worse outcome, meaning more agitation.

  Up to 3 weeks

• Symptoms of Agitation as Measured by the Neuropsychiatric Inventory, Clinician Version

  The Neuropsychiatric Inventory Clinician Version (NPI-C) is an assessment tool used to evaluate neuropsychiatric symptoms in patients, particularly those with dementia. The minimum score is 0 and the max is 426. Higher scores indicate worse outcomes, meaning more agitation.

  Up to 3 weeks

Secondary Outcomes (1)

• Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo

  Up to 3 weeks

Study Arms (2)

Dronabinol

EXPERIMENTAL

Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3.

Drug: Dronabinol (Marinol®)

Placebo

PLACEBO COMPARATOR

Placebo medication will be administered twice daily.

Drug: Placebo

Interventions

Dronabinol (Marinol®) DRUG

5mg - 10mg daily dose

Dronabinol

Placebo DRUG

Daily dose

Placebo

Eligibility Criteria

• Age: 60 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Dementia due to AD
• Presence of Agit-AD as defined by the provisional criteria from the International Psychogeriatric Association (IPA). The definition requires the presence of cognitive impairment, evidence of emotional distress, one of three observable types of behavior (excessive motor activity, verbal aggression, physical aggression), requires that the behavior cause excess disability, and notes that the behaviors cannot be solely attributable to another disorder such as psychiatric illness, medical illness, or effects of substance use.
• Clinically significant severity of agitation defined by NPI-C Agitation or NPI-C Aggression \> 4.
• Able to give informed consent, or deemed to lack such capacity by clinical team and legally authorized representative consents.
• Must be fluent in English and/or Spanish (includes reading, writing, and speech)
• Must be admitted to clinical sites associated with McLean Hospital, Johns Hopkins University, and Miami Jewish Health Services as an inpatient/long term care resident during the study duration (3 weeks) OR be able to travel to these locations to enroll as an outpatient.
• Must be 60-95 years old
• Must begin enrollment in study within one week of being determined eligible

You may not qualify if:

• Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease, which might confound assessment of safety outcomes.
• Seizure disorder
• Baseline delirium as determined by Confusion Assessment Method (CAM) and Diagnostic and Statistical Manual of Mental Disorders (DSM) -5 criteria
• Current use of lithium
• Inability to swallow a pill

Sponsors & Collaborators

• Johns Hopkins University: lead
• Mclean Hospital: collaborator
• Miami Jewish Health: collaborator
• National Institute on Aging (NIA): collaborator
• Tufts Medical Center: collaborator

Study Sites (5)

Miami Jewish Health

Miami, Florida, 33137, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

North Shore Medical Center

Salem, Massachusetts, 01970, United States

Location

Related Publications (4)

• Rosenberg PB, Amjad H, Burhanullah H, Nowrangi M, Vandrey R, Pierre MJ, Outen JD, Schultz M, Marano C, Agronin M, Wilkins JM, Harper D, Laffaye T, Reardon E, Turner K, Ozonsi R, Drury M, Nguyen A, Hasoglu T, Cromwell J, Leoutsakos JM, Forester BP. A Randomized Controlled Trial of the Safety and Efficacy of Dronabinol for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry. 2026 Feb;34(2):167-179. doi: 10.1016/j.jagp.2025.10.011. Epub 2025 Nov 10.

  PMID: 41350162 DERIVED

• Cohen LM, Ash E, Outen JD, Vandrey R, Amjad H, Agronin M, Burhanullah MH, Walsh P, Wilkins JM, Leoutsakos JM, Nowrangi MA, Harper D, Rosenberg PB, Forester BP. Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's dementia (THC-AD). Int Psychogeriatr. 2024 Dec;36(12):1245-1250. doi: 10.1017/S1041610221001150. Epub 2021 Oct 11.

  PMID: 34629131 DERIVED

• Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2.

  PMID: 34532852 DERIVED

• Solomon HV, Greenstein AP, DeLisi LE. Cannabis Use in Older Adults: A Perspective. Harv Rev Psychiatry. 2021 May-Jun 01;29(3):225-233. doi: 10.1097/HRP.0000000000000289.

  PMID: 33660625 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Psychomotor Agitation

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Paul Rosenberg
• Organization: Johns Hopkins University

prosenb9@jhmi.edu

4105509883

Study Officials

• Paul Rosenberg

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Brent Forester

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 7, 2016
• Study Start: March 1, 2017
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: May 9, 2025
• Results First Posted: May 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 1 year of study completion
• Access Criteria: Investigators will send a proposal to the principal investigators (Drs. Rosenberg and Forester) who will decide if the proposal is satisfactory and if so, send the information listed above.

Locations

US (5)