Intranasal Oxytocin for Frontotemporal Dementia

NCT03260920 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: FTDOXY17EF
• Study Type: interventional
• Target: 112
• Locations: 2 countries
• Sites: 11

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.

Conditions

Frontotemporal Dementia

Keywords

oxytocin; frontotemporal dementia; apathy; empathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (3)

Low Dose

EXPERIMENTAL

Drug: Syntocinon

Medium Dose

EXPERIMENTAL

Drug: Syntocinon

High Dose

EXPERIMENTAL

Drug: Syntocinon

Interventions

Syntocinon DRUG

Intranasal Oxytocin

Also known as: Intranasal Oxytocin

High Dose; Low Dose; Medium Dose

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.).

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Weston Brain Institute: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Berry Consultants: collaborator

Study Sites (11)

UCLA

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

University of British Columbia

Vancouver, British Columbia, Canada

Location

Parkwood Institute

London, Ontario, N6C 0A7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

University Health Network

Toronto, Ontario, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

Location

Laval University

Québec, G1J1Z4, Canada

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Frontotemporal Dementia; Lethargy

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Proof-of-Concept Double Blind Randomized Controlled, Cross-Over Adaptive Design Trial

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: August 24, 2017
• Study Start: January 31, 2018
• Primary Completion: June 30, 2023
• Study Completion: December 31, 2024
• Last Updated: December 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); CA (6)