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NCT05742698 | RECRUITING | Frontotemporal Dementia

Nabilone for Agitation in Frontotemporal Dementia
Sponsor:

Simon Ducharme, MD

Information provided by (Responsible Party):

Simon Ducharme, MD

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.

Condition or disease

Frontotemporal Dementia

Frontotemporal Dementia, Behavioral Variant

Primary Progressive Aphasia

bvFTD

PPA

FTD

Intervention/treatment

Nabilone

Placebo

Phase

PHASE2

Detailed Description:

While the search for disease modifying treatment of frontotemporal dementia (FTD) remains elusive, on a day-to-day basis, clinicians struggle to help manage the severe neuropsychiatric symptoms of FTD. Agitation, irritability and aggression are common features of the behavioral variant of FTD and to a lesser extent in primary progressive aphasia, and these symptoms are strongly linked to care partner burden. Unfortunately, current pharmacological options for neuropsychiatric symptoms have limited efficacy. Agitation, aggressive behaviors and irritability in FTD are usually pharmacologically managed with a trial-and-error approach using a combination of trazodone, selective serotonin reuptake inhibitors, antiepileptic drugs, memantine and frequently, antipsychotics. Unfortunately, current pharmacological treatment options for neuropsychiatric symptoms of FTD have limited efficacy and are often based on small case studies or anecdotal evidence. Trazodone has the most support from randomized control trials, but shows limited effectiveness. Therefore, in clinical practice second-generation ('atypical') antipsychotics are commonly used despite a paucity of scientific evidence in FTD. This practice is problematic as antipsychotic use in dementia bears a significant burden of side-effects, including falls, and increased cerebrovascular accidents and mortality. There is a clear need for new treatments using novel mechanisms for neuropsychiatric symptoms in FTD. One promising candidate is nabilone, 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 FTD. We propose to conduct the first randomized clinical trial of nabilone for agitation, irritability, and aggression in FTD to obtain data on real-life effectiveness and tolerability. There is a need to obtain data on the efficacy of nabilone on a wide variety of neuropsychiatric symptoms beyond agitation in FTD, while also ensuring the safety of the medication (e.g., is there a detrimental effect on apathy and hyperorality, which are common in FTD). We require data on dosing and tolerability in this population, which is younger on average than Alzheimer's disease subjects from previous studies and therefore may tolerate higher doses of nabilone. The objective of this trial is to obtain robust evidence for the effectiveness and tolerability of nabilone in FTD.

Study Type : INTERVENTIONAL
Estimated Enrollment : 45 participants
Masking : QUADRUPLE
Masking Description : 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.
Primary Purpose : TREATMENT
Official Title : Double Blind Crossover Clinical Trial of Nabilone for Agitation in Frontotemporal Dementia
Actual Study Start Date : 2023-03-07
Estimated Primary Completion Date : 2026-04
Estimated Study Completion Date : 2026-05

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • * 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
  • Rationale for Inclusion Criteria: The inclusion criteria are designed to enroll patients with FTD with the behaviours of interest, with a range of disease severity that will permit assessment of all outcome measures.
Exclusion Criteria
  • * 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).
  • * Allergy, or significant adverse reaction to cannabinoids. If the adverse reaction involved psychological symptoms that are indicative of psychosis or severe anxiety the patient will be excluded. Their treating clinician may be consulted for a clinical opinion on the severity of the response to cannabis and whether this justifies exclusion from the trial.
  • * 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...)
  • Rationale for Exclusion Criteria: The exclusion criteria are designed to avoid inclusion of patients who may have medical comorbidities that would increase their risk of serious side effects from repeated nabilone administration.
Nabilone for Agitation in Frontotemporal Dementia

Location Details

NCT05742698

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

Canada, British Columbia

University of British Columbia, St Paul's Hospital

Vancouver, British Columbia, Canada, V6z1y6

NOT YET RECRUITING

Canada, Ontario

Brain and Mind Institute, University of Western Ontario

London, Ontario, Canada, 2p6h+GJ

RECRUITING

Canada, Ontario

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, Article 4

ACTIVE NOT RECRUITING

Canada, Ontario

Baycrest Hospital, University of Toronto

Toronto, Ontario, Canada, M6A2E1

RECRUITING

Canada, Ontario

Western Hospital - University of Toronto

Toronto, Ontario, Canada, MH3V+9R

RECRUITING

Canada, Quebec

CHU de Québec, Laval University

Laval, Quebec, Canada, G1V0A6

RECRUITING

Canada, Quebec

The Douglas Research Centre

Montreal, Quebec, Canada, H4H1R3