Nabilone for Frontotemporal Dementia

(Nabilone-FTD Trial)

Recruiting at 6 trial locations

Overseen By Ahmad Fakhoury, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Simon Ducharme, MD

Must not be taking: Cannabinoids, Psychomimetics

Disqualifiers: Psychosis, Orthostatic hypotension, Cardiovascular, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nabilone, a medication, can reduce agitation in individuals with Frontotemporal Dementia (FTD), a type of dementia affecting personality, behavior, and language. Participants will be divided into two groups: one will receive nabilone, and the other will receive a placebo (a pill with no active medicine) for comparison. Suitable candidates for this trial exhibit symptoms of FTD, including frequent agitation, and have maintained a stable medication routine for at least two weeks. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that your psychoactive medication be stable for 1 month before starting and that you do not change the dose during the treatment period. However, ongoing use of any cannabinoid-related products must be stopped.

Is there any evidence suggesting that nabilone is likely to be safe for humans?

Research suggests that nabilone might be a safe option for treating restlessness in people with frontotemporal dementia. Studies have shown that nabilone often causes fewer mental health side effects, such as restlessness, irritability, and confusion. It works similarly to THC but with a milder effect.

People who have used nabilone for other conditions have generally tolerated it well. Few serious side effects have been reported, which is promising for those considering this treatment. As this is a Phase 2 trial, some safety information is available, but more testing is needed to fully understand its effects.

Overall, early findings suggest nabilone could be a well-tolerated treatment for reducing restlessness without causing major side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Frontotemporal Dementia?

Unlike the standard treatments for frontotemporal dementia, which often focus on managing symptoms with antidepressants, antipsychotics, or behavioral therapies, nabilone offers a novel approach. Nabilone is unique because it is a synthetic cannabinoid, similar in structure to THC, the active compound in cannabis. Researchers are excited about nabilone because it may help reduce agitation, a common and challenging symptom of frontotemporal dementia, by interacting with cannabinoid receptors in the brain. This new mechanism of action could provide relief where other treatments fall short, offering a fresh option for patients who struggle with agitation and other behavioral symptoms.

What evidence suggests that nabilone might be an effective treatment for Frontotemporal Dementia?

This trial will compare nabilone, a synthetic form of cannabis, with a placebo to assess its effects on calming individuals with Frontotemporal Dementia (FTD). Research has shown that in past studies, patients who took nabilone experienced less agitation, easing the burden on their caregivers. However, some patients felt very sleepy after taking it. These early results suggest that nabilone could effectively manage agitation in FTD. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Frontotemporal Dementia who experience significant agitation. Participants must be able to consent or have a surrogate decision-maker, not plan to change their psychoactive meds during the trial, and have a study partner available weekly. Excluded are those with allergies to cannabinoids, recent major depression, drug/alcohol abuse history, certain cardiovascular issues, severe liver dysfunction, or other conditions causing agitation.

Inclusion Criteria

You have symptoms of being very restless or agitated due to a cognitive disorder.

I am over 18 years old.

Capacity to provide written consent in English or French, or consent from official surrogate decision maker in case of incapacity

Exclusion Criteria

I have had a major depressive episode in the last 6 months.

I am currently using products that contain cannabinoids.

You are allergic to cannabinoids or had a bad reaction to them before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nabilone or placebo to assess the reduction in agitation over a 6-week period

6 weeks

2 visits (in-person or remote) for interim assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nabilone

Trial Overview

The trial is testing if nabilone can reduce agitation in patients with Frontotemporal Dementia compared to a placebo. It's designed for those meeting specific criteria for behavioral variant FTD or primary progressive aphasia and experiencing notable agitation as per International Psychogeriatric Association standards.

How Is the Trial Designed?

Group I: Nabilone Active Control 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Nabilone is already approved in United States, Canada, United Kingdom for the following indications:

Approved in United States as Cesamet for:

• Chemotherapy-induced nausea and vomiting

Approved in Canada as Cesamet for:

• Chemotherapy-induced nausea and vomiting

Approved in United Kingdom as Cesamet for:

• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Simon Ducharme, MD

Lead Sponsor

Trials

1

Recruited

50+

Alzheimer's Drug Discovery Foundation

Collaborator

Trials

22

Recruited

3,100+

Published Research Related to This Trial

A review of 9 randomized controlled trials found that pharmacological treatments like SSRIs, trazodone, and stimulants may help reduce behavioral symptoms in frontotemporal dementias, but they do not improve cognitive function.

All medications studied were well tolerated by participants, indicating a favorable safety profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatments for frontotemporal dementias: a systematic review of randomized controlled trials. Nardell, M., Tampi, RR.[2022]

Cognitive medications are more frequently prescribed for Alzheimer's disease (AD) patients (78%) compared to frontotemporal dementia (FTD) patients (56%), while psychiatric medications are used more in FTD (68%) than in AD (45%).

The study found significant off-label use of medications in both conditions, but there was no consistent relationship between neuropsychiatric symptoms and medication use, indicating a complex treatment landscape for these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demographic and neuropsychiatric factors associated with off-label medication use in frontotemporal dementia and Alzheimer's disease. Tartaglia, MC., Hu, B., Mehta, K., et al.[2021]

A study involving 2338 Han Chinese subjects found that specific genetic variations (SNPs) in RAB38, HLA-DRA/HLA-DRB5, and BTNL2 are significantly associated with an increased risk of late-onset Alzheimer's disease (AD).

The SNP rs16913634 related to RAB38/CTSC was not linked to AD risk, indicating that not all genetic factors associated with frontotemporal dementia (FTD) also contribute to AD susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Frontotemporal Dementia GWAS Loci with Late-Onset Alzheimer's Disease in a Northern Han Chinese Population. Tan, CC., Wan, Y., Tan, MS., et al.[2022]

A case study of a 61-year-old male with frontotemporal dementia (Pick's disease) showed significant improvement in behavioral and psychological symptoms after three months of treatment with rivastigmine, as indicated by a reduction in the Neuropsychological Inventory score from 36 to 10.

This case supports the potential efficacy of cholinesterase inhibitors like rivastigmine in treating symptoms of frontotemporal dementia, despite limited evidence from previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rivastigmine in a case of autopsy proved frontotemporal dementia (Pick's disease)]. Calatayud-Noguera, T., Astudillo-González, A., Alvarez-Carriles, JC., et al.[2015]

In a 6-month study involving 16 patients with frontotemporal dementia, memantine at a dose of 20 mg/day was well-tolerated but showed limited efficacy, with most patients either unchanged or minimally worse in cognitive and behavioral assessments.

The study indicated a decline in cognitive performance as measured by the Alzheimer's Disease Assessment Scale, suggesting that while memantine is safe, its effectiveness in improving symptoms of frontotemporal dementia remains uncertain and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month, open-label study of memantine in patients with frontotemporal dementia. Diehl-Schmid, J., Förstl, H., Perneczky, R., et al.[2013]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05742698?cond=Behavioral%20variant%20of%20frontotemporal%20dementia%20OR%20%22bv-FTD%22&aggFilters=status:not%20rec&viewType=Table&rank=7

Nabilone for Agitation in Frontotemporal Dementia

The primary goal of this study is to test the hypothesis that oral nabilone treatment will reduce agitation compared with placebo in patients with ...

2.

ctv.veeva.com

ctv.veeva.com/study/nabilone-for-agitation-in-frontotemporal-dementia

Nabilone for Agitation in Frontotemporal Dementia

The primary goal of this study is to test the hypothesis that oral nabilone treatment will reduce agitation compared with placebo in ...

3.

alzdiscovery.org

alzdiscovery.org/research-and-grants/portfolio-details/21533328

McGill University

We propose to conduct the first open-label clinical trial of nabilone for agitation in FTD to obtain data on effectiveness, optimal dose and tolerability. There ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8835388/

Medical cannabinoids for treatment of neuropsychiatric ...

Nabilone treatment was associated with a significant decrease in agitation, besides important reduction in related caregiver burden. Sedation constituted the ...

5.

withpower.com

withpower.com/trial/phase-3-dementia-5-2023-5bb8b

Nabilone for Frontotemporal Dementia (Nabilone-FTD Trial)

The primary goal of this study is to test the hypothesis that oral nabilone treatment will reduce agitation compared with placebo in patients with ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10096227/

Nabilone treatment for severe behavioral problems in ...

Notably, nabilone may have fewer adverse mental health effects such as agitation, irritability and psychosis, because, like THC, it has ...