Intranasal Oxytocin for Frontotemporal Dementia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety, tolerability and effects on behaviour of Syntocinon given intranasally (by a spray into the nostrils) compared to placebo (an inactive saline substance that contains no medication) in participants with frontotemporal dementia/Pick's disease. This study will take place in approximately 15 centres across Canada and the United States. Approximately 112 patients in total will be enrolled in this study. In the first phase we will examine which of three different dosing schedules of oxytocin may be more effective. In the second phase of the study, patients entering the study will be randomized to the oxytocin dosing schedule that appeared most effective in the first phase.

Official Title
-----------------
A Phase 2 Clinical Trial of Intranasal Oxytocin for Frontotemporal Dementia

Conditions
-----------------
Frontotemporal Dementia

Intervention / Treatment
-----------------
* Drug: Syntocinon


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of probable FTD (behavioural variant FTD, FTD-semantic subtype or FTD-Progressive Nonfluent Aphasia) with supportive brain imaging (centrally rated frontotemporal atrophy score of 2 or greater on brain MRI or CT) or known FTD causing genetic mutation.68 Current symptoms of social apathy/indifference as measured by NPI apathy/indifference severity subscale score >= 2 indicating the presence of moderate to marked levels of apathy/indifference. Study partner who consents to study participation and who cares for/visits the patient daily for at least 3 hours/day and who can administer all trial medications. FTLD-CDR score 0-2. MMSE >10. Stable baseline medications related to cognition or behaviour for >=30 days such as acetylcholinesterase inhibitors, memantine, anti-depressants, antipsychotic agents, other mood stabilizers, benzodiazepines. Written informed consent must be obtained and documented (from the patient or, where jurisdictions allow it, from their substitute decision maker). Exclusion Criteria: History of stroke, other neurologic or psychiatric disorder other than FTD that is considered to better account for behavioural symptoms. History of a myocardial infarction within the last two years or congestive heart failure. Current uncontrolled hypertension Current bradycardia (rate < 50 beats per minute/bpm) or tachycardia (rate > 100 bpm) Current hyponatremia (Na <135 mEq/L) Current use of topical prostaglandin medications applied to the cervix. Females who are pregnant or breastfeeding, or planning to conceive within the study period. Use of any investigational or experimental drug or device within the last 60 days prior to screening or within 5 half-lives of the experimental drug, whichever is longer. Participant has speech difficulties that in the opinion of the investigator would be incompatible with neuropsychology and safety assessments History of cancer except: If considered to be cured If not being actively treated with anti-cancer therapy or radiotherapy and, in the opinion of the investigator, not likely to require treatment in the ensuing 5 years For prostate cancer or basal cell carcinoma, no significant progression over the previous 2 years Any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease. If the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included. For the CSF sub-study, current use of anticoagulant medications (warfarin, rivaroxaban, etc.). Plan for FTD patient to be placed into long-term care or plan for hospital admission for any kind of treatment within study period or if caregiver plans for holidays/respite care > 3 days during study period.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A Proof-of-Concept Double Blind Randomized Controlled, Cross-Over Adaptive Design Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br> | Drug: Syntocinon<br>* Intranasal Oxytocin<br>* Other names: Intranasal Oxytocin;|
| Experimental: Medium Dose<br> | Drug: Syntocinon<br>* Intranasal Oxytocin<br>* Other names: Intranasal Oxytocin;|
| Experimental: High Dose<br> | Drug: Syntocinon<br>* Intranasal Oxytocin<br>* Other names: Intranasal Oxytocin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Neuropsychiatric Inventory (NPI) apathy/indifference domain score | Pilot data from our two prior studies of oxytocin in FTD have driven the selection of the NPI as the primary outcome measure. | Up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in emotional facial expression recognition performance |  | Up to 20 weeks | 
| Change in the Revised Self-Monitoring Scale score |  | Up to 20 weeks | 
| Change in modified Clinicians Global Impression of Change (apathy) scores |  | Up to 20 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
frontotemporal dementia, empathy, oxytocin, apathy