Frontotemporal Dementia, Behavioral Variant
Conditions
Keywords
intranasal, insulin
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.
Interventions
DRUGNovolin-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.
Sponsors
HealthPartners Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
41 Years to 89 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility Measured by EXAMINER Battery | Baseline and Post Treatment | Number of patients completing the entire EXAMINER battery. Range: 0-3. More participants completing EXAMINER indicates higher feasibility. |
| Feasibility Measured by Recruitment | Baseline | Number of patients enrolled in this study. Range: 0-12. More participants enrolling indicates higher feasibility. |
| Safety Measured by Total Serious Adverse Events (SAEs) and Adverse Events (AEs) | 2 months | Total number of AEs/SAEs during the course of treatment. More AEs/SAEs indicates a less safe treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility Measured by Completion of Study | 2 months | Number of patients completing the entire study. Range: 0-12. More participants completing the study indicates higher feasibility. |
| Feasibility Measured by Screen Fails | 2 years | Number of patients screen failing during the study. More participants screen failing the study indicates lower feasibility. |
| Safety Measured by Unique Subjects With Serious Adverse Events (SAEs) and Adverse Events (AEs) | 4 weeks | Total number of unique participants experiencing AEs/SAEs during the course of treatment. More unique participants experiencing AEs/SAEs indicates a less safe treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Eating Habits Subscore | 4 weeks | 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. |
| Pre to Post Working Memory Measured by EXAMINER - Dot Counting | 4 weeks | 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. |
| Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Other Oral Behaviors Subscore | 4 weeks | 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. |
| Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Food Preference Subscore | 4 weeks | 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. |
| Pre to Post Verbal Fluency Measured by EXAMINER - Animal Fluency | 4 weeks | 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. |
| Pre to Post Inhibition by EXAMINER - Flanker | 4 weeks | 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. |
| Pre to Post Inhibition by EXAMINER - Set Shifting | 4 weeks | 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. |
| Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Swallowing Subscore | 4 weeks | 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. |
| Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Appetite Subscore | 4 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Insulin (Novolin-R) Regular insulin (Novolin-R) 20 IU/IN (0.1ml/10 units IN in each nostril) BID
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. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Insulin (Novolin-R) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Feasibility Measured by EXAMINER Battery
Number of patients completing the entire EXAMINER battery. Range: 0-3. More participants completing EXAMINER indicates higher feasibility.
Time frame: Baseline and Post Treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin (Novolin-R) | Feasibility Measured by EXAMINER Battery | 3 Participants |
Primary
Feasibility Measured by Recruitment
Number of patients enrolled in this study. Range: 0-12. More participants enrolling indicates higher feasibility.
Time frame: Baseline
Population: The original goal was to include 12 participants. Since this is a feasibility outcome, the analysis population is the original goal total.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin (Novolin-R) | Feasibility Measured by Recruitment | 3 Participants |
Primary
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.
Time frame: 2 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin (Novolin-R) | Safety Measured by Total Serious Adverse Events (SAEs) and Adverse Events (AEs) | 1 Total number of AEs/SAEs reported |
Secondary
Feasibility Measured by Completion of Study
Number of patients completing the entire study. Range: 0-12. More participants completing the study indicates higher feasibility.
Time frame: 2 months
Population: 12 participants were expected. Only 3 participants were able to complete the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin (Novolin-R) | Feasibility Measured by Completion of Study | 3 Participants |
Secondary
Feasibility Measured by Screen Fails
Number of patients screen failing during the study. More participants screen failing the study indicates lower feasibility.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin (Novolin-R) | Feasibility Measured by Screen Fails | 0 Participants |
Secondary
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.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin (Novolin-R) | Safety Measured by Unique Subjects With Serious Adverse Events (SAEs) and Adverse Events (AEs) | 1 Participants |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Appetite Subscore | -0.67 change in score on a scale | Standard Deviation 1.53 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Eating Habits Subscore | 7 change in score on a scale | Standard Deviation 11.3 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Food Preference Subscore | 2.67 change in score on a scale | Standard Deviation 4.62 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Other Oral Behaviors Subscore | 0.33 change in score on a scale | Standard Deviation 3.51 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Appetite Changes by the Appetite and Eating Habit Questionnaire (APEHQ) - Swallowing Subscore | 0.67 change in score on a scale | Standard Deviation 0.53 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Inhibition by EXAMINER - Flanker | -0.145 score on a scale | Standard Deviation 0.26 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Inhibition by EXAMINER - Set Shifting | -0.36 change is score on a scale | Standard Deviation 0.13 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Verbal Fluency Measured by EXAMINER - Animal Fluency | -0.33 named animals | Standard Deviation 3.21 |
Other Pre-specified
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin (Novolin-R) | Pre to Post Working Memory Measured by EXAMINER - Dot Counting | 6.33 score on a scale | Standard Deviation 3.06 |