A phase 2 clinical trial of intranasal oxytocin for frontotemporal dementia
University of Western Ontario
Frontotemporal dementia (FTD) is a progressive neurodegenerative disease for which there is presently no available cure, and only a few off-label symptomatic treatments that are marginally effective. Early in the course of the disease, patients with FTD develop striking deficits in fundamental components of social and emotional behavior including emotional blunting, apathy, and loss of empathy for even their closest family members. As these emotional changes in patients with FTD are among the most burdensome for caregivers, identification of treatments for these symptoms is a critical unmet need. Studies in healthy adults, patients with autism, and our work in patients with FTD suggest oxytocin, a hormone found in the body and brain, may improve the apathy and related empathy deficits in patients with FTD. We aim to conduct a multi-centre, randomized, double blind, placebo controlled trial to determine whether intranasal oxytocin may be an effective treatment for these symptoms in patients with FTD. We will examine different dose schedules of oxytocin to determine if oxytocin improves social apathy and empathy deficits, and whether daily or less frequent dosing is most effective. If effective, oxytocin would be the first symptomatic treatment for patients with FTD specifically targeting the core deficits in social apathy so devastating in this disorder.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
If oxytocin were found to be effective in the present study and a subsequent phase III study, this would have a significant impact on management of patients with FTD and would likely change practice guidelines. If the results are negative, this would still be important information for patients and caregivers as oxytocin can now be purchased over the internet and is increasingly advertised in lay-social media for a variety of conditions. Further, data from the adaptive phase 2 study is anticipated to impact clinical trial design of oxytocin and related compounds in other neuropsychiatric disorders (eg. autism, Alzheimer’s disease, schizophrenia).
At present, the lack of treatments targeting the early apathy/indifference in FTD renders physicians unable to effectively manage the most difficult behaviours for caregivers. The results of this trial will be used to determine whether a follow up full phase III randomized clinical trial required for proof of effectiveness and eventual approval of oxytocin as a treatment for FTD is indicated. If effective, oxytocin would be the first symptomatic treatment for patients with FTD specifically targeting the core deficits in apathy and emotional experience so devastating in this disorder.