Clinical trial NCT04115384: Intranasal Insulin in Frontotemporal Dementia (FTD)
Official title: A Single Center Feasibility Study of Intranasal Insulin in Frontotemporal Dementia NIFT-D
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Frontotemporal Dementia, Behavioral Variant
Keywords: intranasal
insulin
Lead sponsor: HealthPartners Institute
Sponsor class: OTHER
First posted: 2019-10-04
Enrollment: 3
Sex: ALL
Minimum age (years): 41
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This project will study intranasal (IN) insulin in Frontotemporal dementia (FTD) in 12 patients. Study Investigators aim to evaluate the feasibility of the EXAMINER cognitive battery as a cognitive outcome measure in FTD, the ability of the HealthPartners Center for Memory and Aging's ability to sufficiently recruit subjects with FTD, and the safety of IN regular insulin administered 20 IU twice per day in two specific variants of FTD (behavioral variant frontotemporal dementia (bv-FTD), semantic dementia (SD)) over a 4 week period.

Detailed description: Frontotemporal dementia (FTD) with its multiple pathological manifestations, is a disease that results in progressive deterioration of social comportment, executive function, and language. Despite the debilitating nature of FTD and the relatively high prevalence in the younger patient population, available pharmacological interventions are limited to symptomatic treatments. There are no therapeutic agents that have been developed that specifically treat the progressive cognitive symptoms of FTD. This project will study IN insulin in FTD in 12 patients. Investigators aim to evaluate the feasibility of the EXAMINER cognitive battery as a cognitive outcome measure in FTD, the ability of the HealthPartners Center for Memory and Aging's Center's ability to sufficiently recruit subjects with FTD, and the safety of IN regular insulin administered 20 IU twice per day in two specific variants of FTD (behavioral variant frontotemporal dementia (bv-FTD), semantic dementia (SD)) over a 4 week period. Frontotemporal dementia (FTD) with its multiple pathological manifestations, is a disease that results in progressive deterioration of social comportment, executive function, and language. Despite the debilitating nature of FTD and the relatively high prevalence in the younger patient population, available pharmacological interventions are limited to symptomatic treatments. There are no therapeutic agents that have been developed that specifically treat the progressive cognitive symptoms of FTD.

Eligibility criteria: Inclusion Criteria:

1. Male or female subject meeting international consensus criteria for probable behavioral variant frontotemporal dementia or criteria for semantic dementia (Gorno-Tempini et al., 2011; Rascovsky et al., 2011)
2. Subject has a Mini-Mental State Exam (MMSE) score ≥18.
3. Subject is \> 40 and \<90 years of age.
4. Female subjects are post-menopausal or have a negative pregnancy test
5. The subject must be proficient in speaking, reading and understanding English in order to comply with procedural testing of cognitive function, memory and physiology.
6. Subject has a dedicated family member/caregiver, who will be able to attend all visits and report on subject's status.
7. Subject and family member/caregiver have both provided fully informed written consent prior to participation. In the event that subject is legally unable to provide informed written consent due to deterioration in cognitive abilities, fully informed written consent must be provided by a legally authorized representative.
8. Subject must have undergone a brain computed tomography (CT) scan or magnetic resonance imaging (MRI) scan as part of receiving frontotemporal dementia (FTD) diagnosis

Exclusion Criteria:

1. Subject has medical history and/or clinically determined evidence of other central nervous system (CNS) disorders including, but not limited to brain tumor, active subdural hematoma, seizure disorder, multiple sclerosis, Alzheimer's disease, vascular dementia, corticobasal syndrome, progressive supranuclear palsy, Parkinson's disease, multiple system atrophy, Lewy body dementia, normal pressure hydrocephalus, Huntington's disease, or Jakob-Creutzfeldt disease presenting as dementia.
2. Subject has medical history and/or clinically determined disorders: current B12 deficiency, chronic sinusitis, untreated thyroid disease, or significant head trauma.
3. Subject has history of any of the following: moderate to severe pulmonary disease, poorly controlled congestive heart failure, significant cardiovascular and/or cerebrovascular events within previous 6 months, condition known to affect absorption, distribution, metabolism, or excretion of drugs such as any hepatic, renal or gastrointestinal disease or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator.
4. Subject has had previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies.
5. Subject has a history of any psychiatric illness that would pose a safety risk to the subject as determined by investigator.
6. Subject is currently taking any medications (anticholinergics, antihistamines, benzodiazepines, barbiturates, or insulin) that are clinically contraindicated as determined by investigator.
7. Subject has undergone a recent change (\<1 month) in their selective serotonin reuptake inhibitors (SSRI) or anti-depressant medication.
8. Subject has current or recent drug or alcohol abuse or dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders 5, Text Revision (DSM-IV TR).
9. Screening laboratory results that are medically relevant, in which inclusion would pose a safety risk to the subject as determined by investigator.
10. The subject has participated in a clinical trial investigation within 1 month of this study.
11. The subject has an insulin allergy.

Primary outcomes:
measure: Feasibility Measured by EXAMINER Battery
timeFrame: Baseline and Post Treatment
measure: Feasibility Measured by Recruitment
timeFrame: Baseline
measure: Safety Measured by Total Serious Adverse Events (SAEs) and Adverse Events (AEs)
timeFrame: 2 months
Secondary outcomes:
measure: Feasibility Measured by Completion of Study
timeFrame: 2 months
measure: Feasibility Measured by Screen Fails
timeFrame: 2 years
measure: Safety Measured by Unique Subjects With Serious Adverse Events (SAEs) and Adverse Events (AEs)
timeFrame: 4 weeks
Other outcomes:
measure: Pre to Post Working Memory Measured by EXAMINER - Dot Counting
timeFrame: 4 weeks
measure: Pre to Post Verbal Fluency Measured by EXAMINER - Animal Fluency
timeFrame: 4 weeks
measure: Pre to Post Inhibition by EXAMINER - Flanker
timeFrame: 4 weeks
measure: Pre to Post Inhibition by EXAMINER - Set Shifting
timeFrame: 4 weeks
measure: Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Swallowing Subscore
timeFrame: 4 weeks
measure: Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Appetite Subscore
timeFrame: 4 weeks
measure: Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Eating Habits Subscore
timeFrame: 4 weeks
measure: Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Food Preference Subscore
timeFrame: 4 weeks
measure: Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Other Oral Behaviors Subscore
timeFrame: 4 weeks
Locations:
city: Saint Paul
country: United States
facility: HealthPartners Neuroscience Center
state: Minnesota
Study officials:
affiliation: HealthPartners Neurology
name: Michael H Rosenbloom, MD
role: PRINCIPAL_INVESTIGATOR
References: