Nabilone for Agitation Blinded Intervention Trial
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age55+
SponsorSunnybrook Health Sciences Centre
About this trial
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
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Nabilone
DrugAfter 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.
Placebo
Other interventionAfter 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.
Treatment groups
112 Participants
are divided into 2 treatment groupsGroup A: Nabilone ArmExperimental treatment 1 intervention
Group B: Placebo ArmPlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
Baseline (0 Weeks) to 8 WeeksSecondary outcomes
1
Behaviour - Neuropsychiatric Inventory - Nursing Home (NPI-NH)
A widely used assessment of behaviour disturbances in dementia, including: apathy, agitation, delusions, hallucinations, depression, euphoria, aberrant motor behaviour, irritability, disinhibition, anxiety, sleeping, and eating. The frequency and severity of these symptoms are judged on a 4-point and 3-point scale, respectively. Scores range from 0-144 points, with a higher score indicating a worse outcome.
Time frame
Baseline (0 Weeks) to 8 Weeks2
Cognition - Standardized Mini-Mental State Examination (sMMSE)
Measures global cognition, and assesses orientation to time and place, immediate recall, short-term verbal memory, calculation, language, and construct ability. Scores range from 0-30 points, with a lower score indicating a worse outcome.
Time frame
Baseline (0 Weeks) to 8 Weeks3
Weight
Time frame
Baseline (0 Weeks) to 8 Weeks4
Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
A structured interview consisting of 6 items that categorizes patients as malnourished, at risk of malnutrition, or of normal nutritional status. Scores range from 0-14 points, with a lower score indicating a worse outcome.
Time frame
Baseline (0 Weeks) to 8 WeeksOther outcomes
1
Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale
Sedation will be measured using the Sleepiness/Sedation subscale of the UKU-Side Effect Rating Scale. The UKU is a clinician-rated scale that assesses the side effects of psychopharmacological medications. Scores range from 0-3, with a higher score indicating more sleepiness/sedation.
Time frame
Baseline (0 Weeks) to 8 WeeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Sunnybrook Health Sciences Centre
Lead sponsor
Alzheimer's Drug Discovery Foundation
Collaborator
Source ClinicalTrials.gov