Nabilone for Agitation in Alzheimer's Disease

(NAB-IT Trial)

Recruiting at 5 trial locations

Overseen By NAB-IT Coordinating Centre

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: Cognitive enhancers

Must not be taking: Antidepressants, Cannabis

Disqualifiers: Cardiovascular disease, Liver disease, Psychiatric disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: 8 weeks

112 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if nabilone, a synthetic cannabinoid, can reduce agitation in individuals with Alzheimer's disease (AD). Agitation is a common and distressing symptom for those with AD, often leading to quicker institutionalization and increased caregiver stress. The trial will compare nabilone to a placebo to assess improvements in agitation, overall mental health, caregiver stress, cognitive skills, nutrition, and pain. Individuals diagnosed with major neurocognitive disorder due to Alzheimer's and experiencing significant agitation may be suitable for this trial. Participants will receive either nabilone or a placebo for 8 weeks, followed by an additional 8 weeks of follow-up. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but if you are taking cognitive-enhancing medications, your dosage must be stable for at least 3 months before joining. Also, you should not have changed any psychotropic medications within 1 week before starting the trial.

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

Research has shown that nabilone, a synthetic cannabis-like drug, may help reduce agitation in people with Alzheimer's. In a past study with 38 participants, those who took nabilone experienced less agitation, and their caregivers felt less stressed compared to those who took a placebo. Some participants felt more sleepy with nabilone, but it was generally well-tolerated.

Nabilone is already approved in Canada to treat nausea and vomiting in people undergoing chemotherapy, indicating that its safety is well-understood. Although more research is needed to confirm its safety for Alzheimer's patients, the early results are promising. This information can help prospective trial participants consider the possible risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's disease?

Nabilone is unique because it offers a new approach to treating agitation in Alzheimer's patients by using a synthetic cannabinoid. Unlike standard treatments like antipsychotics or benzodiazepines, which can come with serious side effects, nabilone might provide relief with potentially fewer adverse effects. Researchers are excited because nabilone works by targeting the body's endocannabinoid system, which may help modulate mood and behavior more effectively. This fresh mechanism of action could offer a safer, more effective way to manage agitation, improving quality of life for patients and caregivers alike.

What evidence suggests that nabilone might be an effective treatment for agitation in Alzheimer's disease?

Research has shown that nabilone, a synthetic compound similar to one found in cannabis, might help reduce restlessness in people with Alzheimer's disease. An earlier study demonstrated that nabilone noticeably improved restlessness and overall behavior while reducing caregiver stress compared to a placebo. In this trial, participants will receive either nabilone or a placebo at random. Although nabilone appears promising, it can cause side effects like drowsiness, so careful monitoring is important. These results provide a strong basis for further research into using nabilone to treat restlessness in Alzheimer's patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Krista L. Lanctot, PhD

Principal Investigator

Sunnybrook Research Institute

Giovanni Marotta, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for men and women over 55 with Alzheimer's who experience significant agitation. Women must be post-menopausal, and participants should have a stable dose of cognitive-enhancing meds for at least 3 months. They need a caregiver who speaks English well. People using cannabis recently, on certain drugs, or with uncontrolled heart disease or liver issues can't join.

Inclusion Criteria

I experience severe restlessness as defined by health professionals.

My medication for memory or thinking problems has been the same for the last 3 months.

I am a man or a post-menopausal woman aged 55 or older.

Exclusion Criteria

You have used marijuana or other cannabis products for fun in the 3 months before the study starts.

I am not allergic to cannabis or its products and do not have drug interactions.

You currently have symptoms that meet the criteria for a major depressive episode according to the DSM 5.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either nabilone or a placebo for 8 weeks to assess the effectiveness of nabilone in treating agitation and other outcomes in Alzheimer's disease patients.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nabilone
• Placebo

Trial Overview The study tests if nabilone helps reduce agitation in Alzheimer's patients compared to a placebo over an 8-week period. It also examines its effects on neuropsychiatric symptoms, caregiver stress, cognition, nutrition, and pain. Participants are randomly assigned to either the drug or placebo group.

How Is the Trial Designed?

Group I: Nabilone Arm Experimental Treatment 1 Intervention

Participants randomized to the nabilone arm will be titrated up to a maximum dose of 2 mg/day.

Group II: Placebo Arm Placebo Group 1 Intervention

Participants randomized to the placebo arm will receive placebo 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?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Alzheimer's Drug Discovery Foundation

Collaborator

Trials

22

Recruited

3,100+

Weston Brain Institute

Collaborator

Trials

13

Recruited

990+

Published Research Related to This Trial

A clinical trial is underway to evaluate nabilone, a synthetic cannabinoid, for treating agitation in patients with moderate-to-severe Alzheimer's disease, comparing its effects to a placebo over 6 weeks.

The study aims to assess not only the efficacy in reducing agitation but also the safety and potential benefits on pain, weight, and overall quality of life, which could help reduce caregiver stress and healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ruthirakuhan, MT., Herrmann, N., Gallagher, D., et al.[2022]

In a 14-week study involving 38 patients with Alzheimer's disease, the cannabinoid nabilone was associated with reduced agitation, particularly in patients with lower levels of the inflammatory marker TNF-α.

The study suggests that oxidative stress and neuroinflammation are linked to agitation severity in Alzheimer's patients, and nabilone may exert anti-inflammatory effects that contribute to its efficacy in reducing agitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agitation, Oxidative Stress, and Cytokines in Alzheimer Disease: Biomarker Analyses From a Clinical Trial With Nabilone for Agitation. Ruthirakuhan, M., Herrmann, N., Andreazza, AC., et al.[2020]

In a 14-week study involving 39 patients with moderate-to-severe Alzheimer's disease, nabilone significantly reduced agitation compared to placebo, as measured by the Cohen Mansfield Agitation Inventory.

While nabilone showed promise in reducing agitation and caregiver distress, it also caused more sedation, indicating that monitoring for sedation and cognitive effects is important when using this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease. Herrmann, N., Ruthirakuhan, M., Gallagher, D., et al.[2020]

The CitAD study, involving 200 individuals with Alzheimer's disease and significant agitation, evaluated the efficacy of citalopram compared to a placebo, aiming to provide a potential treatment option for this common neuropsychiatric symptom.

The study's design, which included structured psychosocial therapy for caregivers and robust outcome measures, highlights important considerations for future trials assessing psychotropic medications for agitation in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram for agitation in Alzheimer's disease: design and methods. Drye, LT., Ismail, Z., Porsteinsson, AP., et al.[2022]

In a pilot study involving 26 nursing home residents with Alzheimer's disease, buspirone (15 mg) was found to reduce agitation and anxiety more effectively than haloperidol (1.5 mg) over a 10-week period.

While the study lacked a placebo group, the results indicate that buspirone may be a promising option for managing agitation in Alzheimer's patients, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buspirone vs. Haloperidol: A Double-Blind Trial for Agitation in a Nursing Home Population With Alzheimer's Disease. Cantillon, M., Brunswick, R., Molina, D., et al.[2019]

Citalopram was found to be effective in reducing agitation in Alzheimer's disease, showing superior results compared to placebo in both primary response measures after 9 weeks of treatment.

The study highlighted that a longer treatment duration of at least 9 weeks is necessary to observe the full benefits of citalopram, as many patients showed a delayed response, particularly in the later stages of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease. Weintraub, D., Drye, LT., Porsteinsson, AP., et al.[2022]

In two 12-week studies involving a total of 703 patients with agitation in Alzheimer's dementia, brexpiprazole at a dose of 2 mg/day showed significant improvement in agitation symptoms compared to placebo, indicating its efficacy in this patient population.

Brexpiprazole was generally well tolerated, with most treatment-emergent adverse events being mild to moderate, although headaches and insomnia were reported more frequently than with placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials. Grossberg, GT., Kohegyi, E., Mergel, V., et al.[2021]

In a study involving 149 participants with moderate-to-severe Alzheimer's disease, memantine did not show a significant improvement in clinically significant agitation compared to placebo after 6 weeks, indicating it may not be effective for this symptom.

However, memantine did demonstrate a positive effect on cognitive function and showed some benefits in reducing neuropsychiatric symptoms, suggesting it may still have a role in managing other aspects of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial. Fox, C., Crugel, M., Maidment, I., et al.[2022]

Citalopram has shown promising efficacy in treating agitation in Alzheimer's disease dementia, potentially benefiting from a class effect seen in selective serotonin reuptake inhibitors, but concerns about its cardiac side effects have limited its use.

The article reviews safety and efficacy data for both citalopram and escitalopram, providing practical recommendations and risk mitigation strategies to enhance their use in clinical practice for managing agitation in dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When and How to Treat Agitation in Alzheimer's Disease Dementia With Citalopram and Escitalopram. Aga, VM.[2022]

Nabilone, an orally active cannabinoid, significantly reduces nausea and vomiting in 50 to 70% of patients experiencing severe gastrointestinal toxicity from chemotherapy, especially when conventional treatments fail.

While nabilone is more effective and preferred over prochlorperazine for symptom control, it has a high incidence of side effects, including drowsiness and dizziness, affecting 60 to 70% of patients, though serious side effects leading to discontinuation are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nabilone. A preliminary review of its pharmacological properties and therapeutic use. Ward, A., Holmes, B.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31182351/

Randomized Placebo-Controlled Trial of Nabilone ... - PubMed Conclusions: Nabilone may be an effective treatment for agitation. However, sedation and cognition should be closely monitored. Keywords: Alzheimer's disease ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1064748119303550

Randomized Placebo-Controlled Trial of Nabilone for ... Nabilone was shown to improve agitation, overall behavior, and caregiver distress compared to placebo. While sedation was greater in nabilone treatment group, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02351882

Safety and Efficacy of Nabilone in Alzheimer's Disease In addition to these potentially beneficial effects on appetite and pain, a recent study suggested positive effects of nabilone on agitation in dementia.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04516057

Nabilone for Agitation Blinded Intervention Trial They found that nabilone significantly improved agitation, overall neuropsychiatric symptoms, and caregiver distress. That study was limited by its sample size ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6627000/

Investigating the safety and efficacy of nabilone for the ... Another cross-over RCT with dronabinol in 2 patients with AD reported a reduction in night-time agitation during the active treatment phase.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31338476/

Study protocol for a cross-over randomized controlled trial We describe a clinical trial investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to- ...