Nabilone for Agitation in Frontotemporal Dementia

NCT05742698 | Recruiting Phase 2 DMC

• 1 other identifier: Nabilone-FTD
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

The primary goal of this study is to test the hypothesis that oral nabilone treatment will reduce agitation compared with placebo in patients with Frontotemporal Dementia (both behavioural variant frontotemporal dementia and primary progressive aphasia). The study population is defined as patients with probable Frontotemporal Dementia that meet the International Psychogeriatric Association criteria for agitation in cognitive disorders.

Conditions

Frontotemporal Dementia; Frontotemporal Dementia, Behavioral Variant; Primary Progressive Aphasia; bvFTD; PPA; FTD

Keywords

Nabilone; Nabilone FTD; Agitation; TEVA Nabilone; Dementia; BvFTD; FTD

Outcome Measures

Primary Outcomes (1)

• Cohen Mansfield Agitation Inventory (CMAI)

  A scale that is completed by a caregiver with at lest 10 hours of weekly contact with the patient. This scale evaluates a range of symptoms that fall into the category of agitation.

  The patients CMAI score will be compared between their Baseline Assessment (prior to starting treatment) and the outcome Assessment (after 6 weeks of treatment) to determine whether agitation has changed across the treatment period.

Secondary Outcomes (2)

• Tumor necrosis factor alpha (TNFα)

  Is TNFα associated with CMAI scores at baseline or with change in CMAI scores after 6-weeks of nabilone treatment (i.e. between Baseline and Outcome Assessments)?

• 4-hydroxynonenal (4-HNE)

  Is 4-HNE associated with CMAI scores at baseline or with change in CMAI scores after 6-weeks of nabilone treatment (i.e. between Baseline and Outcome Assessments)?

Other Outcomes (1)

• Adverse drug reaction (ADR) to varying doses of nabilone

  Count the number of adverse drug reactions that occur accross the 6 week nabiolne treatment period to determine how well this medication is tolerated in this patient population.

Study Arms (2)

Nabilone

ACTIVE COMPARATOR

Weeks 1-2 Nabilone and placebo will be taken orally by the patient as per the schedule provided by the research team. All patients will start with one 0.5mg capsule per day, taken before bed for the first week and then increase administration to the 1mg capsule taken before bed for the second week. Weeks 3-4 Two weeks after the start of the trial patients and study partners will attend an in person or remote Interim Assessment. If remission is not achieved and no clinically significant adverse drug reactions are reported then the dose schedule will increase to 2 capsules per day (2mg/day), 1 capsule in the morning and 1 before bed. Weeks 5-6 Four weeks after the start of the trial there will be a second in person or remote Interim Assessment identical to the first. If remission of agitation has not been achieved and no adverse drug reactions are reported the dose schedule will increase to 4 tablets per day (4mg/day), with 2 tablets in the morning and 2 before bed.

Drug: Nabilone

Placebo

PLACEBO COMPARATOR

Weeks 1 and 2 Participants will receive one capsule per day to be taken orally before bedtime. Weeks 3-4 Participants will receive 2 capsules per day, one in the morning and one before bedtime. Weeks 5-6 Participants will receive 2 capsules per day, one in the morning and one before bedtime. The placebo dosing regimen is designed to be as similar as possible to the nabilone dosing regime, including using identical capsules.

Drug: Placebo

Interventions

Nabilone DRUG

Nabilone is a synthetic cannabinoid that has shown benefit for agitation in Alzheimer's disease. Nabilone further has potentially beneficial properties on oxidative stress and inflammation in neurodegenerative diseases, mechanisms that have been linked to the pathophysiology of frontotemporal dementia.

Also known as: Nabilone Oral Capsule, TEVA Nabilone

Nabilone

Placebo DRUG

The placebo is a capsule identical to the nabilone capsules that will be used in this clinical trial.

Placebo

Eligibility Criteria

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

You may qualify if:

• Men and women over 18 years
• Major neurocognitive disorder due to probable behavioural variant FTD (Rascovsky criteria)17 or primary progressive aphasia (Gorno-Tempini criteria)18. All ages and severity levels will be included.
• Meets International Psychogeriatric Association criteria for agitation in cognitive disorders19
• CMAI score of 39 or above
• Stable psychoactive medication for 2 weeks prior to screening (all medications allowed) with no intention to change dose during treatment period
• Available study partner with ≥10 hours per week in-person contact with the patient. This can either be a friend/family member or a staff member at an assisted living facility.
• Capacity to provide written consent in English or French, or consent from official surrogate decision maker in case of incapacity

You may not qualify if:

• Clinically significant psychotic symptoms (Neuropsychiatric Inventory domain score (severity x frequency) ≥4 on the delusions or hallucinations subscale)
• Clinically significant orthostatic hypotension (a decrease in systolic blood pressure of 20 mm Hg or in diastolic blood pressure of 10 mm Hg within three minutes of standing compared to blood pressure in a seated position)
• Symptomatic orthostatic tachycardia (heart rate increase from of at least 30 beats per minute within the first 5 minutes of standing compared to a seated position IF orthostatic hypotension is not a problem)
• Unstable cardiovascular condition in the opinion of the investigator
• Known or suspected history of drug or alcohol dependence or abuse in the past 12 months, including use of any psychomimetic drugs (e.g. ketamine, lysergic acid diethylamide, psilocybin).
• Major depressive episode within 6 months of screening
• Women who are breast feeding or pregnant
• Severe liver dysfunction, as determined by their treating clinician
• Other psychiatric or neurological condition that could cause significant agitation
• Ongoing use of any cannabinoid-related products. This includes any THC or CBD based products, regardless of administration method (oral, inhalation, topical, etc…)

Sponsors & Collaborators

• Simon Ducharme, MD: lead
• Alzheimer's Drug Discovery Foundation: collaborator

Study Sites (7)

University of British Columbia, St Paul's Hospital

Vancouver, British Columbia, V6Z1Y6, Canada

RECRUITING

Brain and Mind Institute, University of Western Ontario

London, Ontario, 2P6H+GJ, Canada

NOT YET RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

Baycrest Hospital, University of Toronto

Toronto, Ontario, M6A2E1, Canada

ACTIVE NOT RECRUITING

Western Hospital - University of Toronto

Toronto, Ontario, MH3V+9R, Canada

RECRUITING

CHU de Québec, Université Laval

Laval, Quebec, G1V0A6, Canada

RECRUITING

The Douglas Research Centre

Montreal, Quebec, H4H1R3, Canada

RECRUITING

MeSH Terms

Conditions

Frontotemporal Dementia; Pick Disease of the Brain; Aphasia, Primary Progressive; Psychomotor Agitation; Dementia

Interventions

nabilone

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dyskinesias; Psychomotor Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Central Study Contacts

Simon Ducharme, MD, MA

CONTACT

15144305748; simon.ducharme@mcgill.ca

Ahmad Fakhoury, MA

CONTACT

5147616131; ahmad.fakhoury.comtl@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomized using variable block sizes concealed from participating sites. Central randomization will be done with the database and project manager software, REDCap. After consent and screening, study staff will enter disease severity into the electronic data capture system randomization module so the research pharmacist will be notified via email of study ID and disease severity. Participants will be randomly assigned to receive either Nabilone or placebo for the first treatment phase.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, McGill University

Model Details: This is a multi-centre double blind, placebo-controlled randomized cross-over study comparing 6 weeks of nabilone treatment to 6 weeks of placebo with a 3-week washout between periods. The study will involve an established network of up to 8 FTD centres in Canada.

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: February 24, 2023
• Study Start: March 7, 2023
• Primary Completion: April 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)