Alzheimer's DiseasePhase 2NCT01436045

Safety and Effectiveness Study of Intranasal Insulin Glulisine on Cognitive and Memory in Mild-Mod AD Patients.

A Phase 2 study testing Insulin glulisine and Saline in people with Alzheimer's Disease, run by HealthPartners Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to investigate the effect of the rapidly acting intranasal insulin derivative (glulisine) on memory and cognition in 12 patients suffering from mild-moderate Alzheimer's Disease (AD) using a double-blind placebo-controlled single dose study. Read more about this study

Who is it for?: Ages 65 to 85 years
Conditions the study is for: Alzheimer's Disease
What is being tested?: Insulin glulisine and Saline
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 12 participants
Where: 1 siteUnited States
Study dates: Sep 2011to Jun 2013
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 65 to 85 years
All sexes
No healthy volunteers
Older adult

Who may be able to join

Male or female subject with a clinical diagnosis of probable 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 and Dementia Rating Scale (McKhann 1984).
Mini-Mental State Examination (MMSE) score of 18-26.
Hachinski Ischemia Score < 4.
Age is > 65 and <85 years
Females must be > 2 years post-menopausal or surgically sterile.
Must be able to speak, read and understand English in order to comply with testing of cognitive function, memory and physiology.

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Must have a dedicated family member /caregiver, able to attend all visits and report on subject's status.
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.
On a stable dose (≥ 1 months) of a prescribed acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) and/or memantine.
A brain CT or MRI in the last 2 years compatible with the diagnosis of probable Alzheimer's Disease.
A Clinical Dementia Rating (CDR) ranging from 1 to 2.

Who cannot join

Medical history and/or clinically determined evidence of other central nervous system (CNS) disorders including 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.
Personal medical history and/or clinically determined disorders: current B12 deficiency, positive syphilis serology, chronic sinusitis or any untreated thyroid disease, significant head trauma, or history of difficulty with smell and/or taste prior to AD diagnosis.
Diagnosis with any form of diabetes mellitus, actively takes insulin, or has HbA1c > 6.1 % at screening.
Personal history of any of the following: moderate to severe pulmonary disease, congestive heart failure, significant cardiovascular and/or cerebrovascular events in 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.
Heavy smoker (defined as smoking half a pack or more per day in the last 10 years prior to entry in the study).
Personal history of any psychiatric illness, except major depressive disorder (according to Diagnostic and Statistical Manual (DSM)-IV TR) currently in remission or stable with treatment for > 2 years, or any other psychiatric condition that inclusion would pose a safety risk to the subject as determined by Investigator. Patients with active depression (Geriatric Depression Score>9) are excluded from the study.

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Currently taking any medications, herbals and food supplements that are determined by Investigator to interfere with procedural testing of cognitive function as well as ensure study safety.
Recent change (< 1 months) in prescribed acetylcholinesterase inhibitor (e.g. donepezil, rivastigmine, galantamine) or memantine.
Current or recent drug or alcohol abuse or dependence defined by DSM-IV TR.
Systolic blood pressure > 160 or < 90 mmHg or diastolic blood pressure > 100 or < 60 mmHg at Screening.
Screening laboratory results that are medically relevant and which would pose a safety risk to the subject as determined by Investigator.
Participation in any other research study at least 3 months prior to this study.
Insulin allergy.
History of significant traumatic brain injury
History of acute and chronic rhinitis and/or sinusitis.
Legally unable to provide informed written consent due to deterioration in cognitive abilities.

Trial locations and contacts

1 site in 1 country.

United States1 site

HealthPartners Specialty Center - Center for Dementia & Alzheimer's Care
Saint Paul, Minnesota, 55130

Other trials in United States

About this study

Official title: A Double-Blind, Placebo-Controlled Single Dose Study of the Safety and Efficacy of Glulisine on Cognitive Function and Memory in Individuals Diagnosed With Probable Mild to Moderate Alzheimer's Disease/Intranasal Insulin Study.

Read the detailed description

A single center, phase II randomized, double-blind, placebo-controlled, cross-over study designed to assess the efficacy and safety of intranasally (IN) delivered insulin glulisine versus placebo in patients aged 65-85 with mild-moderate Alzheimer's Disease (AD). Twelve AD subjects (six female and six male) will be randomized to receive a single dose of either 20 IU/IN insulin glulisine or placebo using the MAD 300 device.

Conditions: Alzheimer's Disease
Being tested: Insulin glulisine, Saline
Keywords: Memory, Insulin glulisine, Alzheimer's Disease
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Insulin glulisineDrug
Also called Apidra
Single treatment, 20 IU/Intranasal (.1ml/10 units Intranasally in each nostril)
SalineDrug
Also called salt water
Single treatment,(saline) 20 IU/Intranasal (.1ml/10units intranasally in each nostril)

Study groups in NCT01436045
Study group	Role	What they receive
Insulin glulisine	Experimental	A randomized, double-blind, placebo-controlled, cross-over designed - all subject will receive intervention (insulin glulisine) and placebo (saline) during separate visits. Receives: Drug: Insulin glulisine
Saline	Placebo comparator	A randomized, double-blind, placebo-controlled, cross-over designed - all subject will receive intervention (insulin glulisine) and placebo (saline) during separate visits. Receives: Drug: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

Cognitive Performance
The results are presented as a mean number of correct responses for each cognitive assessment.
For each of these, a lower number correct is indicative of a higher cognitive deficit.
Ranges are as follows: RBANS List Learning (0-40), RBANS Story Memory (0-24), RBANS Figure Copy (0-20), RBANSLine Orientation (0-20), RBANS Semantic Fluency (0-unlimited), RBANS List Recall (0-10), RBANS List Recognition (0-20), RBANS Story Recall (0-12), RBANS Figure Recall (0-20), Digit Span Forward (0-16), Digit Span Backward (0-16), Boston Naming (0-15).
Measured: 20 minutes post-intranasal administration
Trails B - Seconds
The results are presented as the number of seconds to complete Trails B. For each of these, a higher number of seconds is indicative of a higher cognitive deficit.
Measured: 20 minutes post-intranasal administration
Trails B - Errors
The results are presented as the mean sum of the errors during the Trails B assessment For each of these, a higher number of errors is indicative of a higher cognitive deficit.
Measured: 20 minutes post-intranasal administration

Secondary outcomes (1)

Olfactory Function
The Sniff Magnitude Test (SMT) measures olfactory function not influenced by cognitive problems (minimal dependence on language, cognitive ability, memory, and odor naming ability). Sniff magnitude ratios are calculated as a ratio of sniff magnitudes (area under the sniff curve). Lower sniff magnitude ratios indicate more impairment.
[average sniff magnitude of malodor/average sniff magnitude to a null odor]
Measured: 60 minute post intranasal administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011Jun 2013

First posted19 Sep 2011 (estimated)
Study startSep 2011
Primary completionJun 2013
Study completionJun 2013

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.
Other trials for Alzheimer's DiseaseStudies 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: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01436045
Sponsor's protocol ID: 11-111
Status last verified: Sep 2015
First submitted: 16 Sep 2011
Last updated: 19 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind, Placebo-Controlled Single Dose Study of the Safety and Efficacy of Glulisine on Cognitive Function and Memory in Individuals Diagnosed With Probable Mild to Moderate Alzheimer's Disease/Intranasal Insulin Study.
ClinicalTrials.gov ID: NCT01436045
Acronym / sponsor ID: 11-111
Conditions: Alzheimer's Disease
Keywords: Memory, Insulin glulisine, Alzheimer's Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: HealthPartners InstituteUniversity, hospital or other
Study start: Sep 2011
Primary completion: Jun 2013 (actual)
Study completion: Jun 2013 (actual)
First posted: 19 Sep 2011 (estimated)
Results: Posted 19 Oct 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Insulin glulisine	Experimental	Drug: Insulin glulisineA randomized, double-blind, placebo-controlled, cross-over designed - all subject will receive intervention (insulin glulisine) and placebo (saline) during separate visits.
Saline	Placebo comparator	Drug: SalineA randomized, double-blind, placebo-controlled, cross-over designed - all subject will receive intervention (insulin glulisine) and placebo (saline) during separate visits.

Who may qualify

Ages: 65 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (11 listed)

Male or female subject with a clinical diagnosis of probable 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 and Dementia Rating Scale (McKhann 1984).
Mini-Mental State Examination (MMSE) score of 18-26.
Hachinski Ischemia Score < 4.
Age is > 65 and <85 years
Females must be > 2 years post-menopausal or surgically sterile.

Key exclusion criteria (16 listed)

Medical history and/or clinically determined evidence of other central nervous system (CNS) disorders including 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.
Personal medical history and/or clinically determined disorders: current B12 deficiency, positive syphilis serology, chronic sinusitis or any untreated thyroid disease, significant head trauma, or history of difficulty with smell and/or taste prior to AD diagnosis.
Diagnosis with any form of diabetes mellitus, actively takes insulin, or has HbA1c > 6.1 % at screening.
Personal history of any of the following: moderate to severe pulmonary disease, congestive heart failure, significant cardiovascular and/or cerebrovascular events in 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.
Heavy smoker (defined as smoking half a pack or more per day in the last 10 years prior to entry in the study).

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: ApidraSingle treatment, 20 IU/Intranasal (.1ml/10 units Intranasally in each nostril)	Drug	Insulin glulisine
SalineAlso: salt waterSingle treatment,(saline) 20 IU/Intranasal (.1ml/10units intranasally in each nostril)	Drug	Saline

Primary outcome

Cognitive Performance
Time frame: 20 minutes post-intranasal administration
The results are presented as a mean number of correct responses for each cognitive assessment. For each of these, a lower number correct is indicative of a higher cognitive deficit. Ranges are as follows: RBANS List Learning (0-40), RBANS Story Memory (0-24), RBANS Figure Copy (0-20), RBANSLine Orientation (0-20), RBANS Semantic Fluency (0-unlimited), RBANS List Recall (0-10), RBANS List Recognition (0-20), RBANS Story Recall (0-12), RBANS Figure Recall (0-20), Digit Span Forward (0-16), Digit Span Backward (0-16), Boston Naming (0-15).
Trails B - Seconds
Time frame: 20 minutes post-intranasal administration
The results are presented as the number of seconds to complete Trails B. For each of these, a higher number of seconds is indicative of a higher cognitive deficit.
Trails B - Errors
Time frame: 20 minutes post-intranasal administration
The results are presented as the mean sum of the errors during the Trails B assessment For each of these, a higher number of errors is indicative of a higher cognitive deficit.

1 secondary outcome

Olfactory Function
Time frame: 60 minute post intranasal administration

Results and safety

Results posted to the registry on 19 Oct 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Insulin Glulisine, Then Placebo	6	6
Placebo, Then Insulin Glulisine	6	6

Primary outcome: Cognitive Performance

Time frame: 20 minutes post-intranasal administration. Mean (Standard Error). Unit: mean total correct responses

Measure	Post-Insulin Glulisine n = 12	Post-Placebo n = 12
RBANS List Learning	15.92 (1.32)	16.67 (2.02)
RBANS Story Memory	8.58 (1.17)	8.41 (1.55)
RBANS Figure Copy	16.58 (0.98)	16.92 (3.42)
RBANS Line Orientation	14.25 (0.97)	12.25 (1.38)
RBANS Semantic Fluency	12.25 (1.38)	12.5 (1.75)
RBANS List Recall	0.83 (0.42)	1.0 (0.51)
RBANS List Recognition	14.92 (0.69)	14.75 (0.97)
RBANS Story Recall	2.12 (0.96)	2.33 (0.90)

Post-Insulin Glulisine vs Post-Placebo: Percent Change: -15.7, p <0.05, t-test, 2 sided

Primary outcome: Trails B - Seconds

Time frame: 20 minutes post-intranasal administration. Mean (Standard Error). Unit: mean seconds

Measure	Post-Insulin Glulisine n = 12	Post-Placebo n = 12
Value	166.83 (20.82)	177.25 (21.65)

Primary outcome: Trails B - Errors

Time frame: 20 minutes post-intranasal administration. Mean (Standard Error). Unit: mean number of errors

Measure	Post-Insulin Glulisine n = 12	Post-Placebo n = 12
Value	1.17 (0.27)	2.08 (0.31)

Post-Insulin Glulisine vs Post-Placebo: Mean Difference (Final Values): 0.92, p <0.05, t-test, 2 sided

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Study Partipants	0 of 12 (0%)	0 of 12 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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

1 site 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 and Saline in people with Alzheimer's Disease, run by HealthPartners Institute at 1 site 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 11 inclusion and 16 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: finished, as of the sponsor's last update on 19 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 19 Oct 2015). 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?

Cognitive Performance (time frame: 20 minutes post-intranasal administration). 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 NCT01436045.

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 19 Oct 2015.