Clinical trial NCT03260920: Intranasal Oxytocin for Frontotemporal Dementia
Official title: A Phase 2 Clinical Trial of Intranasal Oxytocin for Frontotemporal Dementia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Frontotemporal Dementia
Keywords: oxytocin
frontotemporal dementia
apathy
empathy
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Weston Brain Institute
name: Canadian Institutes of Health Research (CIHR)
name: Berry Consultants
First posted: 2017-08-24
Enrollment: 112
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A Proof-of-Concept Double Blind Randomized Controlled, Cross-Over Adaptive Design Trial
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in Neuropsychiatric Inventory (NPI) apathy/indifference domain score
timeFrame: Up to 20 weeks
Secondary outcomes:
measure: Change in emotional facial expression recognition performance
timeFrame: Up to 20 weeks
measure: Change in the Revised Self-Monitoring Scale score
timeFrame: Up to 20 weeks
measure: Change in modified Clinicians Global Impression of Change (apathy) scores
timeFrame: Up to 20 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Quebec
country: Canada
facility: Laval University
Study officials:
References:
citation: Finger E, Berry S, Cummings J, Coleman K, Hsiung R, Feldman HH, Boxer A. Adaptive crossover designs for assessment of symptomatic treatments targeting behaviour in neurodegenerative disease: a phase 2 clinical trial of intranasal oxytocin for frontotemporal dementia (FOXY). Alzheimers Res Ther. 2018 Sep 27;10(1):102. doi: 10.1186/s13195-018-0427-2.