Safety and Efficacy of Nabilone in Alzheimer's Disease

NCT02351882 | Completed Phase 2 DMC

• 1 other identifier: 318-2013
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease (AD) is commonly associated with behavioural changes such as agitation. Severe agitation is important to treat because it not only increases progression of AD and physical health problems (increased falls and weight loss), but it also decreases quality of life and increases caregiver stress. Currently prescribed treatments (i.e., antipsychotics) for agitation in AD do not work in everybody and when they do work the effect is small and they increase the risk of harmful side effects, including death. As a result, there is an urgent need for safer medication options. The cannabinoid nabilone can now be prescribed in capsule form for appetite and pain killing effects. Nabilone's calming effects may benefit those with agitation, and help the weight loss and untreated pain frequently associated with agitation. Through a clinical trial, the investigators hope identify the benefits of nabilone in the treatment of agitation in AD. The investigators objective is to determine whether nabilone is an efficacious and safe treatment for agitation, as well as having benefits for pain, weight and behavioural symptoms. This will be a 14 week clinical trial (participants take nabilone for 6 weeks, placebo for 6 weeks (order randomized) with 1 week between treatments). The investigators will assess and compare agitation, weight, pain, memory, behaviour and safety. Nabilone is a new class of medication that may be a safe and effective treatment for agitation in AD, with added benefits on appetite and pain. Reducing these symptoms would increase quality-of-life and reduce caregiver stress.

Conditions

Alzheimer Disease; Agitation; Weight Loss; Pain; Oxidative Stress

Outcome Measures

Primary Outcomes (1)

• Change in 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.

  baseline (0 weeks) to 14 weeks

Secondary Outcomes (5)

• Change in neuropsychiatric symptoms; Neuropsychiatric Inventory (NPI)

  baseline (0 weeks) to 14 weeks

• Change in cognition; Standardized Mini-mental State Examination (sMMSE)

  baseline (0 weeks) to 14 weeks

• Change in cognition; Severe Impairment Battery (SIB)

  baseline (0 weeks) to 14 weeks

• Change in cognition; Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)

  baseline (0 weeks) to 14 weeks

• Change in clinical representation; Alzheimer's Disease Cooperative Study - The Clinician Global Impression (ADCS - CGIC)

  2 to 14 weeks

Other Outcomes (5)

• Change in pain; Pain Assessment In Advanced Dementia (PAINAD)

  baseline (0 weeks) to 14 weeks

• Change in nutritional status; Mini Nutritional Assessment - Short Form (MNA-SF)

  baseline (0 weeks) to 14 weeks

• Change in heart rate

  baseline (0 weeks) to 14 weeks

Study Arms (2)

Nabilone

ACTIVE COMPARATOR

Participants randomized into the nabilone arm will be prescribed nabilone for 6 weeks. After one-week placebo washout, they will be taking placebo for an additional 6 weeks.

Drug: Nabilone

Placebo

PLACEBO COMPARATOR

Participants randomized into the placebo arm will be receiving placebo for 6 weeks. After one-week placebo washout, they will be prescribed nabilone for an additional 6 weeks.

Drug: Placebo

Interventions

Nabilone DRUG

Participants randomized to nabilone treatment arm, will undergo a one-week placebo washout, followed by 6 weeks of nabilone treatment (weeks 1-6). Participants will then receive a one-week placebo washout (week 7), before receiving 6 weeks of placebo treatment (weeks 8-14).

Nabilone

Placebo DRUG

Participants randomized to placebo arm, will undergo a one-week placebo washout, followed by 6 weeks of drug matched placebo (weeks 1-6). Participants will then receive a one-week placebo washout (week 7), before receiving 6 weeks of nabilone treatment (weeks 8-14).

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females ≥55 years of age
• Diagnostic and Statistical Manual (DSM) -V criteria for Major Neurocognitive Disorder due to AD. Patients with both Major Neurocognitive Disorder due to AD and Major Vascular Neurocognitive Disorder (i.e., mixed AD and cerebrovascular disease) will also be included.
• Currently in moderate-to-severe stage of dementia (Mini-Mental Status Examination (MMSE) ≤24)
• Presence of clinically significant agitation (Neuropsychiatric Inventory (NPI) agitation subscale ≥3)
• If treated with cognitive-enhancing medications (cholinesterase inhibitors and/or memantine), dosage must be stable for at least 3 months. If the ChEI and/or memantine has been discontinued, they may enroll after 1 month.

You may not qualify if:

• Change in psychotropic medications less than 1 month prior to study randomization (e.g., concomitant antidepressants)
• Contraindications to nabilone (history of hypersensitivity to any cannabinoid)
• Current or past significant cardiovascular disease (e.g. uncontrolled hypertension, ischemic heart disease, arrhythmia and severe heart failure)
• Presence or history of other psychiatric disorders or neurological conditions (e.g. psychotic disorders, schizophrenia, stroke, epilepsy), previous or current abuse of/dependence on marijuana

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (6)

• Ruthirakuhan MT, Herrmann N, Gallagher D, Andreazza AC, Kiss A, Verhoeff NPLG, Black SE, Lanctot KL. Investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe Alzheimer's disease: Study protocol for a cross-over randomized controlled trial. Contemp Clin Trials Commun. 2019 May 23;15:100385. doi: 10.1016/j.conctc.2019.100385. eCollection 2019 Sep.

  PMID: 31338476 BACKGROUND

• 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.

  PMID: 31182351 RESULT

• Ruthirakuhan M, Herrmann N, Andreazza AC, Verhoeff NPLG, Gallagher D, Black SE, Kiss A, Lanctot KL. 24S-Hydroxycholesterol Is Associated with Agitation Severity in Patients with Moderate-to-Severe Alzheimer's Disease: Analyses from a Clinical Trial with Nabilone. J Alzheimers Dis. 2019;71(1):21-31. doi: 10.3233/JAD-190202.

  PMID: 31322567 RESULT

• Ruthirakuhan M, Herrmann N, Andreazza AC, Verhoeff NPLG, Gallagher D, Black SE, Kiss A, Lanctot KL. Agitation, Oxidative Stress, and Cytokines in Alzheimer Disease: Biomarker Analyses From a Clinical Trial With Nabilone for Agitation. J Geriatr Psychiatry Neurol. 2020 Jul;33(4):175-184. doi: 10.1177/0891988719874118. Epub 2019 Sep 23.

  PMID: 31547752 RESULT

• Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2.

  PMID: 34532852 DERIVED

• Ruthirakuhan M, Lanctot KL, Vieira D, Herrmann N. Natural and Synthetic Cannabinoids for Agitation and Aggression in Alzheimer's Disease: A Meta-Analysis. J Clin Psychiatry. 2019 Jan 29;80(2):18r12617. doi: 10.4088/JCP.18r12617.

  PMID: 30753761 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Psychomotor Agitation; Weight Loss; Pain

Interventions

nabilone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Body Weight Changes; Body Weight

Study Officials

• Krista L. Lanctôt, PhD

  Sunnybrook Research Institute

  PRINCIPAL INVESTIGATOR

• Nathan Herrmann, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: January 30, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: March 1, 2019
• Last Updated: June 25, 2020

Record last verified: 2020-06

Locations

CA (1)