Nabilone for Agitation Blinded Intervention Trial (NAB-IT)
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| ClinicalTrials.gov Identifier: NCT04516057 |
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Recruitment Status :
Recruiting
First Posted : August 17, 2020
Last Update Posted : February 21, 2022
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alzheimer Disease Agitation | Drug: Nabilone Other: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 112 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Nabilone for Agitation Blinded Intervention Trial |
| Actual Study Start Date : | February 1, 2021 |
| Estimated Primary Completion Date : | October 2025 |
| Estimated Study Completion Date : | October 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Nabilone Arm
Participants randomized to the nabilone arm will be titrated up to a maximum dose of 2 mg/day.
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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 Name: Cesamet |
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Placebo Comparator: Placebo Arm
Participants randomized to the placebo arm will receive placebo capsules.
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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. |
- 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.
- 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.
- 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.
- Weight [ Time Frame: 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.
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 55 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
- 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)
- Current reported recreational use of marijuana or other cannabis products
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04516057
| Contact: NAB-IT Coordinating Centre | 416-480-6100 ext 5630 | NAB-IT@sunnybrook.ca |
| Canada, Alberta | |
| University of Calgary | Recruiting |
| Calgary, Alberta, Canada, T2N 4N1 | |
| Contact: Ramnik Sekhon ramnik.sekhon@ucalgary.ca | |
| Canada, Ontario | |
| Sunnybrook Health Sciences Centre | Recruiting |
| Toronto, Ontario, Canada, M4N 3M5 | |
| Contact: Abby Li Abby.Li@sunnybrook.ca | |
| Centre for Addiction and Mental Health | Not yet recruiting |
| Toronto, Ontario, Canada | |
| St. Michael's Hospital | Not yet recruiting |
| Toronto, Ontario, Canada | |
| Ontario Shores Centre for Mental Health Sciences | Recruiting |
| Whitby, Ontario, Canada, L1N 5S9 | |
| Contact: Elaina Niciforos niciforose@ontarioshores.ca | |
| Principal Investigator: | Krista L. Lanctôt, PhD | Sunnybrook Research Institute | |
| Principal Investigator: | Nathan Herrmann, MD | Sunnybrook Health Sciences Centre | |
| Principal Investigator: | Giovanni Marotta, MD | Sunnybrook Health Sciences Centre |
| Responsible Party: | Sunnybrook Health Sciences Centre |
| ClinicalTrials.gov Identifier: | NCT04516057 |
| Other Study ID Numbers: |
1968 |
| First Posted: | August 17, 2020 Key Record Dates |
| Last Update Posted: | February 21, 2022 |
| Last Verified: | February 2022 |
| 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 |
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Cannabis Cannabinoid THC |
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Alzheimer Disease Psychomotor Agitation Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders Dyskinesias Neurologic Manifestations |
Psychomotor Disorders Neurobehavioral Manifestations Nabilone Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs |