Clinical trial NCT04516057: Nabilone for Agitation Blinded Intervention Trial
Official title: Nabilone for Agitation Blinded Intervention Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease
Agitation
Keywords: Cannabis
Cannabinoid
THC
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Alzheimer's Drug Discovery Foundation
First posted: 2020-08-17
Enrollment: 112
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Males or females ≥55 years of age; females must be post-menopausal
2. 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
3. sMMSE ≤24
4. Presence of clinically significant agitation based on the IPA definition
5. If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months prior to study randomization
6. 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Agitation - Cohen-Mansfield Agitation Inventory (CMAI)
timeFrame: Baseline (0 Weeks) to 8 Weeks
Secondary outcomes:
measure: Behaviour - Neuropsychiatric Inventory - Nursing Home (NPI-NH)
timeFrame: Baseline (0 Weeks) to 8 Weeks
measure: Cognition - Standardized Mini-Mental State Examination (sMMSE)
timeFrame: Baseline (0 Weeks) to 8 Weeks
measure: Weight
timeFrame: Baseline (0 Weeks) to 8 Weeks
measure: Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
timeFrame: Baseline (0 Weeks) to 8 Weeks
measure: Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate-II (PACSLAC-II)
timeFrame: Baseline (0 Weeks) to 8 Weeks
measure: Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)
timeFrame: Baseline (0 Weeks) to 8 Weeks
Other outcomes:
measure: Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale
timeFrame: Baseline (0 Weeks) to 8 Weeks
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Whitby
country: Canada
facility: Ontario Shores Centre for Mental Health Sciences
state: Ontario
Study officials:
affiliation: Sunnybrook Research Institute
name: Krista L. Lanctot, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Giovanni Marotta, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.