Nabilone for Agitation Blinded Intervention Trial

NCT04516057 | Recruiting Phase 3 DMC

• 1 other identifier: 1968
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 6

Brief Summary

This study will look at whether nabilone is an effective treatment for agitation in Alzheimer's disease (AD) patients. Agitation is highly prevalent in patients with AD and is one of the most distressing and challenging-to-treat symptoms. Agitation is associated with faster progression to institutionalization, increased caregiver burden, poorer quality of life, and increased risk of death. In addition, current pharmacological options show only modest efficacy and elevated risks of adverse events. Therefore, identifying safer and more effective treatments for agitation in AD is a clinical and research priority. Nabilone is a synthetic cannabinoid that is Health Canada-approved to treat chemotherapy-induced nausea and vomiting. The PI's research group completed a 6-week double-blind placebo-controlled randomized cross-over pilot trial in 38 patients with moderate-to-severe AD, providing the first preliminary evidence regarding the safety and efficacy of nabilone in this population. They found that nabilone significantly improved agitation, overall neuropsychiatric symptoms, and caregiver distress. That study was limited by its sample size and questions remain regarding the efficacy of nabilone for nutrition and pain and predictors of response. However, the promising preliminary findings encourage a pivotal, practice-changing phase III trial to inform clinical practice. Participants in this study will be randomized to receive either nabilone or a placebo for 8 weeks. In addition to looking at the effectiveness of nabilone in treating agitation, the researchers will also look at whether it is beneficial for other relevant outcomes for patients with AD including overall neuropsychiatric symptoms, caregiver distress, cognition, nutritional status, and pain. Participants will also be followed for 8 weeks following completion of the study treatment.

Conditions

Alzheimer Disease; Agitation

Keywords

Cannabis; Cannabinoid; THC

Outcome Measures

Primary Outcomes (1)

• Agitation - Cohen-Mansfield Agitation Inventory (CMAI)

  A 29-point scale that measures agitation in two dimensions, verbal and physical, each of which having two poles, aggressive and non-aggressive. Scores range from 29-203 points, with a higher score indicating a worse outcome. This includes the CMAI IPA Agitation Score \& CMAI IPA Delphi Modification, which are derived from the CMAI.

  Baseline (0 Weeks) to 8 Weeks

Secondary Outcomes (6)

• Behaviour - Neuropsychiatric Inventory - Nursing Home (NPI-NH)

  Baseline (0 Weeks) to 8 Weeks

• Cognition - Standardized Mini-Mental State Examination (sMMSE)

  Baseline (0 Weeks) to 8 Weeks

• Weight

  Baseline (0 Weeks) to 8 Weeks

• Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)

  Baseline (0 Weeks) to 8 Weeks

• Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate-II (PACSLAC-II)

  Baseline (0 Weeks) to 8 Weeks

Other Outcomes (1)

• Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale

  Baseline (0 Weeks) to 8 Weeks

Study Arms (2)

Nabilone Arm

EXPERIMENTAL

Participants randomized to the nabilone arm will be titrated up to a maximum dose of 2 mg/day.

Drug: Nabilone

Placebo Arm

PLACEBO COMPARATOR

Participants randomized to the placebo arm will receive placebo capsules.

Other: Placebo

Interventions

Nabilone DRUG

After the screening period, participants randomized to the nabilone arm will receive nabilone for 8 weeks. Participants will then be followed for 8 weeks following completion of the study treatment.

Also known as: Cesamet

Nabilone Arm

Placebo OTHER

After the screening period, participants randomized to the placebo arm will receive placebo capsules for 8 weeks. Participants will then be followed for 8 weeks following completion of the study treatment.

Placebo Arm

Eligibility Criteria

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

You may qualify if:

• Males or females ≥55 years of age; females must be post-menopausal
• Diagnostic and Statistical Manual of Mental Disorders-5 (DSM 5) criteria for Major Neurocognitive Disorder due to AD. Patients with Major Neurocognitive Disorder due to multiple etiologies (AD and vascular) will be included
• sMMSE ≤24
• Presence of clinically significant agitation based on the IPA definition
• If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months prior to study randomization
• Availability of a primary caregiver to accompany the participant to study visits and to participate in the study. The primary caregiver must be sufficiently proficient in English to complete the required study assessments, as per investigator judgement.

You may not qualify if:

• Change in psychotropic medications less than 1 week prior to study randomization (e.g., concomitant antidepressants)
• Contraindications to cannabinoids, e.g. allergies to cannabis and cannabis products, potential clinically important drug-drug interactions
• Current uncontrolled cardiovascular disease (e.g. uncontrolled hypertension, ischemic heart disease, arrhythmia and severe heart failure), as per investigator assessment
• Current significant liver disease, as per investigator assessment
• Presence or history of other psychiatric disorders or neurological conditions (e.g. psychotic disorders, schizophrenia, stroke, epilepsy)
• Participants currently meeting DSM 5 criteria for Major Depressive Episode (MDE)
• Previous or current abuse of/dependence on marijuana
• Clinically significant delusions and/or hallucinations (NPI-NH delusion/hallucinations subscore ≥4)
• Reported recreational use of marijuana or other cannabis products within 3 months prior to study randomization

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Alzheimer's Drug Discovery Foundation: collaborator

Study Sites (6)

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

RECRUITING

St. Michael's Hospital

Toronto, Ontario, Canada

RECRUITING

Ontario Shores Centre for Mental Health Sciences

Whitby, Ontario, L1N 5S9, Canada

RECRUITING

Related Publications (1)

• Herrmann N, Ruthirakuhan M, Gallagher D, Verhoeff NPLG, Kiss A, Black SE, Lanctot KL. Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry. 2019 Nov;27(11):1161-1173. doi: 10.1016/j.jagp.2019.05.002. Epub 2019 May 8.

  PMID: 31182351 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Psychomotor Agitation; Marijuana Abuse

Interventions

nabilone

Condition Hierarchy (Ancestors)

Dementia; 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; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Krista L. Lanctot, PhD

  Sunnybrook Research Institute

  PRINCIPAL INVESTIGATOR

• Giovanni Marotta, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NAB-IT Coordinating Centre

CONTACT

416-480-6100; NAB-IT@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: August 5, 2020
• First Posted: August 17, 2020
• Study Start: February 1, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

CA (6)