Intranasal Oxytocin for Frontotemporal Dementia (FOXY)

A Phase 2 Clinical Trial of Intranasal Oxytocin for Frontotemporal Dementia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Frontotemporal Dementia
• Intervention / Treatment: Drug: Syntocinon

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1J1Z4
    • Laval University
  • British Columbia
    • Vancouver, British Columbia, Canada
      • University of British Columbia
  • Ontario
    • London, Ontario, Canada, N6C 0A7
      • Parkwood Institute
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada
      • University Health Network
  • Quebec
    • Montreal, Quebec, Canada
      • Montreal Neurological Institute and Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Dose	Drug: Syntocinon; Intranasal Oxytocin; Other Names: Intranasal Oxytocin
Experimental: Low Dose	Drug: Syntocinon; Intranasal Oxytocin; Other Names: Intranasal Oxytocin
Experimental: Medium Dose	Drug: Syntocinon; Intranasal Oxytocin; 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	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

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: Canadian Institutes of Health Research (CIHR); Berry Consultants; Weston Brain Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): June 30, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 19, 2017
• First Submitted That Met QC Criteria: August 22, 2017
• First Posted (Actual): August 24, 2017

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: oxytocin; apathy; empathy; frontotemporal dementia
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: FTDOXY17EF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No