Nabilone for Agitation Blinded Intervention Trial (NAB-IT)

July 24, 2023 updated by: Sunnybrook Health Sciences Centre

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

112

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
      • Toronto, Ontario, Canada
        • Recruiting
        • St. Michael's Hospital
      • Toronto, Ontario, Canada
        • Recruiting
        • Centre for Addiction and Mental Health
      • Whitby, Ontario, Canada, L1N 5S9

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nabilone Arm
Participants randomized to the nabilone arm will be titrated up to a maximum dose of 2 mg/day.
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 Names:
  • Cesamet
Placebo Comparator: Placebo Arm
Participants randomized to the placebo arm will receive placebo capsules.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Agitation - Cohen-Mansfield Agitation Inventory (CMAI)
Time Frame: Baseline (0 Weeks) to 8 Weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Behaviour - Neuropsychiatric Inventory - Nursing Home (NPI-NH)
Time Frame: Baseline (0 Weeks) to 8 Weeks
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
Cognition - Standardized Mini-Mental State Examination (sMMSE)
Time Frame: Baseline (0 Weeks) to 8 Weeks
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
Weight
Time Frame: Baseline (0 Weeks) to 8 Weeks
Baseline (0 Weeks) to 8 Weeks
Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
Time Frame: Baseline (0 Weeks) to 8 Weeks
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
Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate-II (PACSLAC-II)
Time Frame: Baseline (0 Weeks) to 8 Weeks
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
Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)
Time Frame: Baseline (0 Weeks) to 8 Weeks
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale
Time Frame: Baseline (0 Weeks) to 8 Weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Alzheimer's Drug Discovery Foundation
Weston Brain Institute

Investigators

  • Principal Investigator: Giovanni Marotta, MD, Sunnybrook Health Sciences Centre
  • Principal Investigator: Krista L. Lanctôt, PhD, Sunnybrook Research Institute
  • Principal Investigator: Nathan Herrmann, MD, Sunnybrook Health Sciences Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2021

Primary Completion (Estimated)

October 1, 2025

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

August 5, 2020

First Submitted That Met QC Criteria

August 14, 2020

First Posted (Actual)

August 17, 2020

Study Record Updates

Last Update Posted (Actual)

July 25, 2023

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1968

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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