Back to resultsNabilone for Agitation Blinded Intervention Trial (NAB-IT)
Primary Purpose
Alzheimer Disease, Agitation
Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Nabilone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease focused on measuring Cannabis, Cannabinoid, THC
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- University of CalgaryRecruiting
- Sunnybrook Health Sciences CentreRecruiting
- Centre for Addiction and Mental HealthRecruiting
- St. Michael's HospitalRecruiting
- Ontario Shores Centre for Mental Health SciencesRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Nabilone Arm
Placebo Arm
Arm Description
Participants randomized to the nabilone arm will be titrated up to a maximum dose of 2 mg/day.
Participants randomized to the placebo arm will receive placebo capsules.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Weight
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.
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.
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.
Full Information
NCT ID
NCT04516057
First Posted
August 5, 2020
Last Updated
July 24, 2023
Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Alzheimer's Drug Discovery Foundation, Weston Brain Institute
1. Study Identification
Unique Protocol Identification Number
NCT04516057
Brief Title
Nabilone for Agitation Blinded Intervention Trial
Acronym
NAB-IT
Official Title
Nabilone for Agitation Blinded Intervention Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Alzheimer's Drug Discovery Foundation, Weston Brain Institute
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Agitation
Keywords
Cannabis, Cannabinoid, THC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Nabilone Arm
Arm Type
Experimental
Arm Description
Participants randomized to the nabilone arm will be titrated up to a maximum dose of 2 mg/day.
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Participants randomized to the placebo arm will receive placebo capsules.
Intervention Type
Drug
Intervention Name(s)
Nabilone
Other Intervention Name(s)
Cesamet
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Agitation - Cohen-Mansfield Agitation Inventory (CMAI)
Description
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 Weeks
Secondary Outcome Measure Information:
Title
Behaviour - Neuropsychiatric Inventory - Nursing Home (NPI-NH)
Description
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 Weeks
Title
Cognition - Standardized Mini-Mental State Examination (sMMSE)
Description
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 Weeks
Title
Weight
Time Frame
Baseline (0 Weeks) to 8 Weeks
Title
Nutritional Status - Mini Nutritional Assessment - Short Form (MNA-SF)
Description
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 Weeks
Title
Pain - Pain Assessment Checklist for Seniors with Limited Ability to Communicate-II (PACSLAC-II)
Description
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.
Time Frame
Baseline (0 Weeks) to 8 Weeks
Title
Global Change - Alzheimer's Disease Cooperative Study - Clinical Global Impression of Severity/Change (ADCS-CGIS/C)
Description
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.
Time Frame
Baseline (0 Weeks) to 8 Weeks
Other Pre-specified Outcome Measures:
Title
Sedation - Udvalg for Kliniske Undersøgelser (UKU) Side-Effect Rating Scale
Description
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 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
NAB-IT Coordinating Centre
Phone
416-480-6100
Ext
5630
Email
NAB-IT@sunnybrook.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Krista L. Lanctôt, PhD
Organizational Affiliation
Sunnybrook Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nathan Herrmann, MD
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Giovanni Marotta, MD
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramnik Sekhon
Email
ramnik.sekhon@ucalgary.ca
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abby Li
Email
Abby.Li@sunnybrook.ca
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Name
Ontario Shores Centre for Mental Health Sciences
City
Whitby
State/Province
Ontario
ZIP/Postal Code
L1N 5S9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elaina Niciforos
Email
niciforose@ontarioshores.ca
12. IPD Sharing Statement
Citations:
PubMed Identifier
31182351
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.
Results Reference
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Nabilone for Agitation Blinded Intervention Trial
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