Intranasal Oxytocin for Frontotemporal Dementia

• Syntocinon (Drug), also known as Intranasal Oxytocin: Intranasal Oxytocin

Primary outcomes

• Change in Neuropsychiatric Inventory (NPI) apathy/indifference domain score [Up to 20 weeks]: Pilot data from our two prior studies of oxytocin in FTD have driven the selection of the NPI as the primary outcome measure.

Secondary outcomes

• 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]

Sex: All, ages: 30 Years to 80 Years

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.

• Results publication: Coleman KKL, Berry S, Cummings J, Hsiung GR, Laforce R, Huey E, Ducharme S, Tartaglia MC, Mendez MF, Onyike C, Domoto-Reilly K, Masellis M, Herrmann N, Porsteinsson A, Detry MA, Stewart C, Bosse AL, McGlothlin A, Dias B, Pandey S, Mayich M, Pasternak SH, Ruiz Garcia R, Restrepo-Martinez M, Feldman H, Boxer AL, Finger EC. Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial. Lancet Neurol. 2025 Feb;24(2):128-139. doi: 10.1016/S1474-4422(24)00456-3. PMID 39862881
• Results publication: 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. PMID 30261917

• Statistical Analysis Plan (PDF, 2023-11-22)