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

Trial Summary

What is the purpose of this 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 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.

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.

How is the drug Nabilone unique for treating frontotemporal dementia?

Nabilone is unique for treating frontotemporal dementia because it is a synthetic cannabinoid, which is different from the more commonly used treatments like SSRIs, trazodone, and stimulants that focus on behavioral symptoms. This novel approach may offer alternative benefits due to its distinct mechanism of action, although its effectiveness for this specific condition is still being studied. ^{1 2 3 4 5}

Eligibility Criteria

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

I am over 18 years old.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Demographic and neuropsychiatric factors associated with off-label medication use in frontotemporal dementia and Alzheimer's disease. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacological treatments for frontotemporal dementias: a systematic review of randomized controlled trials. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A 6-month, open-label study of memantine in patients with frontotemporal dementia. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Association of Frontotemporal Dementia GWAS Loci with Late-Onset Alzheimer's Disease in a Northern Han Chinese Population. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

[Rivastigmine in a case of autopsy proved frontotemporal dementia (Pick's disease)]. [2015]