Intranasal Insulin in Frontotemporal Dementia (FTD)

A Single Center Feasibility Study of Intranasal Insulin in Frontotemporal Dementia NIFT-D

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.

Study Overview

• Status: Terminated
• Conditions: Frontotemporal Dementia, Behavioral Variant
• Intervention / Treatment: Drug: Novolin-R insulin

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • HealthPartners Neuroscience Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin (Novolin-R); Regular insulin (Novolin-R) 20 IU/IN (0.1ml/10 units IN in each nostril) BID	Drug: Novolin-R insulin; Insulin (Novolin-R) 20 IU/IN (0.1ml/10 units IN in each nostril), twice per day, once in the morning and again in the evening (at least 8 hours between doses) for 4 weeks.; Other Names: insulin, Novolin-R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Measured by EXAMINER Battery	Number of patients completing the entire EXAMINER battery. Range: 0-3. More participants completing EXAMINER indicates higher feasibility.	Baseline and Post Treatment
Feasibility Measured by Recruitment	Number of patients enrolled in this study. Range: 0-12. More participants enrolling indicates higher feasibility.	Baseline
Safety Measured by Total Serious Adverse Events (SAEs) and Adverse Events (AEs)	Total number of AEs/SAEs during the course of treatment. More AEs/SAEs indicates a less safe treatment.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Measured by Screen Fails	Number of patients screen failing during the study. More participants screen failing the study indicates lower feasibility.	2 years
Safety Measured by Unique Subjects With Serious Adverse Events (SAEs) and Adverse Events (AEs)	Total number of unique participants experiencing AEs/SAEs during the course of treatment. More unique participants experiencing AEs/SAEs indicates a less safe treatment.	4 weeks
Feasibility Measured by Completion of Study	Number of patients completing the entire study. Range: 0-12. More participants completing the study indicates higher feasibility.	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre to Post Working Memory Measured by EXAMINER - Dot Counting	Dot counting measures verbal working memory. Participants are asked to count colored shapes on a tables and remember the final total over 6 trials. Scores are totaled as the number of correct answers or the number of answers recalled. Range: 0-27. A higher score indicates better performance.	4 weeks
Pre to Post Verbal Fluency Measured by EXAMINER - Animal Fluency	Participants are asked to name as many animals as he/she can in 60 seconds. Scores are totaled as the number of animals verbalized. A higher score indicates better performance.	4 weeks
Pre to Post Inhibition by EXAMINER - Flanker	Participants are asked to choose the direction of one the center arrow in a group 5 arrows. Range: 0- 10. This is a global score that combines accuracy and reaction time. A higher score indicates better performance.	4 weeks
Pre to Post Inhibition by EXAMINER - Set Shifting	Participants are asked to match stimulus on different parts of a tablet screen. Range: 0- 10. This is a global score that combines accuracy and reaction time. A higher score indicates better performance.	4 weeks
Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Swallowing Subscore	A survey about changes in eating behaviors. The sum of frequency times severity of swallowing related questions is the score for this portion. Caregivers of participant are asked to fill this survey out. Range: 0-96. Higher scores indicate higher difficulty swallowing that produces conflict or embarrassment.	4 weeks
Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Appetite Subscore	A survey about changes in eating behaviors. The sum of frequency times severity of appetite related questions is the score for this portion. Caregivers of participant are asked to fill this survey out Range: 0-96. Higher scores indicate a greater change in appetite that produces conflict or embarrassment.	4 weeks
Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Eating Habits Subscore	A survey about changes in eating behaviors. The sum of frequency times severity of eating habit related questions is the score for this portion. Caregivers of participant are asked to fill this survey out Range: 0-72. Higher scores indicate a greater change in eating habits that produces conflict or embarrassment.	4 weeks
Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Food Preference Subscore	A survey about changes in eating behaviors. The sum of frequency times severity of food preference related questions is the score for this portion. Caregivers of participant are asked to fill this survey out Range: 0-84. Higher scores indicate a greater change in food preferences that produces conflict or embarrassment.	4 weeks
Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Other Oral Behaviors Subscore	A survey about changes in eating behaviors. The sum of frequency times severity of other oral behavior related questions is the score for this portion. Caregivers of participant are asked to fill this survey out Range: 0-60. Higher scores indicate a greater changes that produces conflict or embarrassment.	4 weeks

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Investigators: Principal Investigator: Michael H Rosenbloom, MD, HealthPartners Neurology

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Actual): February 26, 2020
• Study Completion (Actual): May 15, 2023

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 4, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: intranasal; insulin
• 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; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: A18-305

Drug and device information, study documents

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