Nabilone for Agitation Blinded Intervention Trial

Alzheimer Disease Clinical Trial

— NAB-IT  

Official title:

Nabilone for Agitation Blinded Intervention Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04516057
• Other study ID #: 1968
• Status: Recruiting
• Phase: Phase 3
• Start date: February 1, 2021
• Est. completion date: October 2025

Study information

• Verified date: July 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: NAB-IT Coordinating Centre
• Phone: 416-480-6100
• Email: NAB-IT[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Agitation
• Alzheimer Disease
• Psychomotor Agitation

Intervention

Drug:
• Nabilone
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.

Other:
• Placebo
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.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Ontario Shores Centre for Mental Health Sciences	Whitby	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Alzheimer's Drug Discovery Foundation, Weston Brain Institute

Country where clinical trial is conducted

Canada, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Baseline (0 Weeks) to 8 Weeks
Primary	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	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.	Baseline (0 Weeks) to 8 Weeks
Secondary	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.	Baseline (0 Weeks) to 8 Weeks
Secondary	Weight		Baseline (0 Weeks) to 8 Weeks
Secondary	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.	Baseline (0 Weeks) to 8 Weeks
Secondary	Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate-II (PACSLAC-II)	A 31-item observer-rated scale assessing facial expressions, activity/body movements, social/personality/mood indicators and mental status changes. Scores range from 0-31 points, with a higher score indicating a worse outcome.	Baseline (0 Weeks) to 8 Weeks
Secondary	Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)	A commonly-used clinician-rated scale that quantifies disease severity and clinical change (worsening, no change, or improvement), based on information regarding the patient's medical history, cognition, behaviour, and function. Numerical scores are not assigned.	Baseline (0 Weeks) to 8 Weeks