Mild Cognitive ImpairmentPhase 2NCT02503501
Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease
A Phase 2 study testing Insulin glulisine in people with Mild Cognitive Impairment and Alzheimer's Disease (AD), run by HealthPartners Institute at 2 sites in United States.
Trial summary
This study evaluates the safety and effectiveness of intranasal (IN) glulisine in patients with amnestic mild cognitive impairment (aMCI) and probable Alzheimer's disease. Half of participants will receive IN glulisine, while the other half will receive IN placebo. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer's Disease (AD)
- What is being tested?
- Insulin glulisine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Sep 2015to 15 Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is/has
- clinical and research diagnosis of amnestic-MCI OR probable mild AD in accordance with National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
- Montreal Cognitive Assessment (MoCA) score 18-27
- Hachinski Ischemia Score <4
- 50-90 years of age
- Females at least 2 years post-menopausal or surgically sterile
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- Proficiency in speaking, reading and understanding English
- Dedicated family member /caregiver, who will be able to attend all visits and report on subject's status
- (and family member/caregiver) 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
- If AD, a brain computed tomography (CT) or magnetic resonance imaging (MRI) in the initial diagnostic workup or subsequent care that is compatible with the diagnosis of probable AD
Who cannot join
- Subject has/have/is
- 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, dementia with Lewy bodies, vascular dementia, corticobasal syndrome, progressive supranuclear palsy, Parkinson's disease, multiple system atrophy, frontotemporal dementia, normal pressure hydrocephalus, Huntington's disease, or Jakob-Creutzfeldt disease presenting as dementia
- medical history and/or clinically determined disorders: current B12 deficiency, chronic sinusitis, any untreated thyroid disease, significant head trauma and history of difficulty with smell and/or taste prior to AD diagnosis
- 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
- previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies
- history of any psychiatric illness, with the exception of major depressive and anxiety disorder (according to Diagnostic and Statistical Manual of Mental Disorders, version 5, Text Revision (DSM-IV TR)) currently in remission or stable with treatment for > 2 yrs, or any other psychiatric condition that inclusion would pose a safety risk to the subject as determined by investigator
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- currently taking any medications, herbals and food supplements that are medically/clinically contraindicated as determined by investigator in order to comply with procedural testing of cognitive function as well as ensure study safety. See list of prohibited medications and compounds
- undergone a recent change (<1mo) in their prescribed acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) or memantine.
- undergone a recent change (<1mo) in their selective serotonin re-uptake inhibitor (SSRI) or anti-depressant medication
- current or recent drug or alcohol abuse or dependence as defined by DSM-IV TR
- laboratory results that are medically relevant, in which inclusion would pose a safety risk to the subject as determined by investigator
- participated in any other research study at least 3 mos prior to this study
- an insulin allergy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
HealthPartners Riverside
Minneapolis, Minnesota, 55455
HealthPartners Neuroscience Center
Saint Paul, Minnesota, 55130
About this study
Official title: A Phase II, Single Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and the Therapeutic Effectiveness of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease
This study evaluates the safety and effectiveness of intranasal (IN) glulisine in patients with amnestic mild cognitive impairment (aMCI) and probable Alzheimer's disease. Half of participants will receive IN glulisine, while the other half will receive IN placebo.
Read the detailed description
Disruption of central nervous system (CNS) insulin signaling has been increasingly associated with Alzheimer's Disease pathogenesis, and consequently this disease has been referred to as a type III diabetes of the brain. Clinical trials of intranasal insulin in AD have demonstrated therapeutic effects of intranasal (IN) insulin in memory-impaired adults in terms of memory recall without significantly altering serum insulin or glucose levels. In this study, the investigators are investigating the chronic effects of the rapid acting insulin, glulisine, administered intranasally (IN) 20 IU two times daily in adults with amnestic-mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD). The investigation will enroll n=90 subjects and follow them over a 6 month period.
This study has the following objectives:
- Primary:
- To measure the chronic effects of IN insulin glulisine on cognition and function in subjects with aMCI and probable mild AD over a 6 month period.
- Secondary:
- To measure the effect of IN insulin glulisine on mood in subjects with aMCI and mild AD over a 6 month period.
- To measure the safety and efficacy of IN glulisine in aMCI and mild AD subjects with non-insulin dependent diabetes over a 6 month period.
- Exploratory:
- To measure the effect of IN delivery of insulin glulisine on parieto-temporal and posterior cingulate/precuneus glucose metabolism in subjects with aMCI and mild AD over a 6 month period.
- To measure the chronic effect of IN delivery of insulin glulisine on AD-specific cerebrospinal (CSF) biomarkers (Abeta42, tau, and phospho-tau) in subjects with aMCI and mild AD over a 6 month period.
- Being tested
- Insulin glulisine, Placebo
- Keywords
- Memory, Insulin glulisine, Alzheimer's disease, Mild Cognitive Impairment, Intranasal insulin, Cognition Disorders
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin glulisineDrug
Also called Apidra
PlaceboDrug
Also called Saline
Bacteriostatic 0.9% Sodium Chloride
| Study group | Role | What they receive |
|---|---|---|
| Insulin Glulisine | Experimental | Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Receives: Drug: Insulin glulisine |
| Placebo | Placebo comparator | Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13)
The ADAS-Cog was developed as an outcome measure for global cognition in clinical trials for Alzheimer's disease. The ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and orientation. The modified ADAS-Cog 13-item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a total of 85 points (0: no cognitive impairment; 85: severe impairment).
Measured: Baseline and 6 months
Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale
The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). The total CDR ratings for each of the six cognitive/functional domains can be added to create a CDR sum of boxes (SOB). The overall SOB score ranges from 0 to 18; with 18 indicating severe impairment and 0 indicating no impairment.
Measured: Baseline and 6 months
Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ)
The FAQ measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. The FAQ is a sum of scores ranging from 0 (normal) to 30 (complete dependence on others).
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start28 Sep 2015
- Primary completion11 Feb 2019
- Study completion15 Feb 2019
Why it stopped: Study will not have power to show a difference between groups.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- HealthPartners Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael H Rosenbloom, MD, Principal investigator, HealthPartners Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02503501
- Sponsor's protocol ID
- IN-INSUL-MCI-AD
- Status last verified
- Jan 2020
- First submitted
- 14 Jul 2015
- Last updated
- 9 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rosenbloom M, Barclay TR, Kashyap B, Hage L, O'Keefe LR, Svitak A, Pyle M, Frey W, Hanson LR. A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease. Drugs Aging. 2021 May;38(5):407-415. doi: 10.1007/s40266-021-00845-7. Epub 2021 Mar 15.
PubMed 33719017
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and the Therapeutic Effectiveness of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT02503501
- Acronym / sponsor ID
- IN-INSUL-MCI-AD
- Keywords
- Memory, Insulin glulisine, Alzheimer's disease, Mild Cognitive Impairment, Intranasal insulin, Cognition Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study will not have power to show a difference between groups.
- Enrolment
- 49 participants (actual)
- Lead sponsor
- HealthPartners InstituteUniversity, hospital or other
- Study start
- 28 Sep 2015 (actual)
- Primary completion
- 11 Feb 2019 (actual)
- Study completion
- 15 Feb 2019 (actual)
- First posted
- 21 Jul 2015 (estimated)
- Results
- Posted 9 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the safety and effectiveness of intranasal (IN) glulisine in patients with amnestic mild cognitive impairment (aMCI) and probable Alzheimer's disease. Half of participants will receive IN glulisine, while the other half will receive IN placebo.
Detailed description
Disruption of central nervous system (CNS) insulin signaling has been increasingly associated with Alzheimer's Disease pathogenesis, and consequently this disease has been referred to as a type III diabetes of the brain. Clinical trials of intranasal insulin in AD have demonstrated therapeutic effects of intranasal (IN) insulin in memory-impaired adults in terms of memory recall without significantly altering serum insulin or glucose levels. In this study, the investigators are investigating the chronic effects of the rapid acting insulin, glulisine, administered intranasally (IN) 20 IU two times daily in adults with amnestic-mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD). The investigation will enroll n=90 subjects and follow them over a 6 month period.
This study has the following objectives:
- Primary:
- To measure the chronic effects of IN insulin glulisine on cognition and function in subjects with aMCI and probable mild AD over a 6 month period.
- Secondary:
- To measure the effect of IN insulin glulisine on mood in subjects with aMCI and mild AD over a 6 month period.
- To measure the safety and efficacy of IN glulisine in aMCI and mild AD subjects with non-insulin dependent diabetes over a 6 month period.
- Exploratory:
- To measure the effect of IN delivery of insulin glulisine on parieto-temporal and posterior cingulate/precuneus glucose metabolism in subjects with aMCI and mild AD over a 6 month period.
- To measure the chronic effect of IN delivery of insulin glulisine on AD-specific cerebrospinal (CSF) biomarkers (Abeta42, tau, and phospho-tau) in subjects with aMCI and mild AD over a 6 month period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin Glulisine | Experimental | Drug: Insulin glulisineInsulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months |
| Placebo | Placebo comparator | Drug: PlaceboSaline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subject is/has
- clinical and research diagnosis of amnestic-MCI OR probable mild AD in accordance with National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
- Montreal Cognitive Assessment (MoCA) score 18-27
- Hachinski Ischemia Score <4
- 50-90 years of age
Key exclusion criteria (13 listed)
- Subject has/have/is
- 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, dementia with Lewy bodies, vascular dementia, corticobasal syndrome, progressive supranuclear palsy, Parkinson's disease, multiple system atrophy, frontotemporal dementia, normal pressure hydrocephalus, Huntington's disease, or Jakob-Creutzfeldt disease presenting as dementia
- medical history and/or clinically determined disorders: current B12 deficiency, chronic sinusitis, any untreated thyroid disease, significant head trauma and history of difficulty with smell and/or taste prior to AD diagnosis
- 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
- previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin glulisineAlso: Apidra | Drug | Insulin Glulisine |
| PlaceboAlso: SalineBacteriostatic 0.9% Sodium Chloride | Drug | Placebo |
Primary outcome
Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13)
Time frame: Baseline and 6 months
The ADAS-Cog was developed as an outcome measure for global cognition in clinical trials for Alzheimer's disease. The ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and orientation. The modified ADAS-Cog 13-item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a total of 85 points (0: no cognitive impairment; 85: severe impairment).
Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale
Time frame: Baseline and 6 months
The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). The total CDR ratings for each of the six cognitive/functional domains can be added to create a CDR sum of boxes (SOB). The overall SOB score ranges from 0 to 18; with 18 indicating severe impairment and 0 indicating no impairment.
Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ)
Time frame: Baseline and 6 months
The FAQ measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. The FAQ is a sum of scores ranging from 0 (normal) to 30 (complete dependence on others).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33719017Rosenbloom M, Barclay TR, Kashyap B, Hage L, O'Keefe LR, Svitak A, Pyle M, Frey W, Hanson LR. A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease. Drugs Aging. 2021 May;38(5):407-415. doi: 10.1007/s40266-021-00845-7. Epub 2021 Mar 15.
- HealthPartners Center for Memory and AgingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael H Rosenbloom, MD principal investigator
HealthPartners Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Insulin glulisine in people with Mild Cognitive Impairment and Alzheimer's Disease (AD), run by HealthPartners Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13) (time frame: Baseline and 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02503501, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2020; AzTrials last refreshed its copy on 8 Nov 2026.