- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01547169
Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 21 Days (SNIFF-LONG 21)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
It is well-known that insulin, a hormone that is naturally secreted by the pancreas, plays an important physiological role by regulating blood sugar levels in the body. The investigators now know that insulin plays many important roles in the brain as well. Insulin seems to be especially active in the part of the brain that corresponds to learning and memory. Studies have shown that when people have insufficient insulin in the brain (which, for example, is the case with Type-II diabetes), they are increasingly at risk to develop memory problems and Alzheimer's disease. In a past study, the investigators administered intravenous insulin to participants and found that it improves their memory. However, that particular method would not be a practical intervention for people with Alzheimer's disease due to the risk of hypoglycemia or exacerbation of insulin resistance. Instead, the investigators use an "intranasal" method of administration, in which the insulin is inserted into a device, and administered intranasally. In this method, the insulin travels directly to the brain, and bypasses the body. Our past studies have also demonstrated that this can be a reliable way to improve memory, and it does not change the body's blood glucose levels.
In our past studies, the investigators have used regular insulin, which lasts about 3-4 hours and creates a similar "spike" in insulin that one would have after eating a meal. However, in normal physiology, the pancreas also releases small and more constant "pulses" of insulin throughout the day and night, establishing a base level of insulin. Accordingly, several longer-lasting types of insulin are now available that last closer to 10-12 hours, mimicking that base level of insulin. The current study uses a long-lasting type of insulin called "insulin detemir," to determine if learning and memory will benefit from a more constant supplement of insulin. the investigators want to determine whether this treatment can benefit people who already have a memory impairment-either they already have a diagnosis of Alzheimer's disease or are diagnosed with mild cognitive impairment, a condition that precedes Alzheimer's disease, and whether a lower or higher dose of insulin detemir is more effective. The investigators will examine cognition, daily function, and different markers of Alzheimer's disease that are in the blood as outcome measures.
The investigators have these specific aims:
- The investigators will test the hypothesis that compared to placebo, three weeks of treatment with intranasal insulin detemir will improve cognition and function in adults with Alzheimer's Disease (AD) or Mild Cognitive Impairment (MCI).
- The investigators will determine which of two doses of intranasal insulin detemir produces the greatest improvement in cognition and daily function relative to placebo for adults with AD or MCI.
To examine these hypotheses, the investigators are recruiting approximately 60 participants who have been diagnosed with AD or MCI. They will be randomly selected to take a lower dose of insulin detemir, a higher dose of insulin detemir, or saline (which is an inactive substance and will serve as a placebo). Cognition and the level of daily function will be tested before they begin the study drug, and after 3 weeks of the study drug. The investigators will also measure glucose tolerance and take blood samples to measure markers of AD in the blood.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Washington
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Seattle, Washington, United States, 98108
- VA Puget Sound Health Care System
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 50-89
- Diagnosed with mild cognitive impairment, or mild/moderate AD
Exclusion Criteria:
- Excessively high or low blood pressure, heart rate
- BMI greater than 34
- Pre-existing diabetes not controlled by exercise
- Previous/current use of insulin
- Significant elevations in lipids, liver enzymes
- Menstrual period within the last 12 months
- Significant neurological or medical disorder (other than AD)
- Significant use of nasal decongestants
- Current use of anti-psychotic, anti-convulsive, anxiolytic, glucocorticoids, or sedative medications
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Saline
|
saline, taken twice per day for a 3 week duration
|
Experimental: Low Dose Insulin Detemir (10IU bid)
|
10IU of insulin detemir, administered intranasally twice per day for a 3 week duration
Other Names:
20IU insulin detemir, administered intranasally twice per day for a 3 week duration
Other Names:
|
Experimental: High Dose Insulin Detemir (20IU bid)
|
10IU of insulin detemir, administered intranasally twice per day for a 3 week duration
Other Names:
20IU insulin detemir, administered intranasally twice per day for a 3 week duration
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Verbal Memory Composite
Time Frame: Change from Baseline in Verbal Memory at 3 Weeks
|
The composite will consist of the weighted sum of Immediate + Delayed Story Recall and Immediate +Delayed List Recall
|
Change from Baseline in Verbal Memory at 3 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neuropsychological Test of Executive Function 1
Time Frame: Change from Baseline in Executive Functioning at 3 Weeks
|
Computerized Dot Counting Test (test of executive functioning)
|
Change from Baseline in Executive Functioning at 3 Weeks
|
Glucose Tolerance
Time Frame: Change from Baseline in Glucose Tolerance at 3 Weeks
|
Subjects will undergo oral glucose tolerance test (OGTT) to assess glucose tolerance
|
Change from Baseline in Glucose Tolerance at 3 Weeks
|
Functional Ability
Time Frame: Change from Baseline in Functional Ability at 3 Weeks
|
Subjects will have a collateral informant (i.e., spouse or friend) rate the subjects' ability to carry out activities of daily living on the Dementia Severity Rating Scale.
|
Change from Baseline in Functional Ability at 3 Weeks
|
Plasma biomarkers of AD
Time Frame: Change from Baseline in Plasma Biomarkers at 3 Weeks
|
Plasma Abeta (ABeta 38, ABeta 40, and Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.
|
Change from Baseline in Plasma Biomarkers at 3 Weeks
|
Neuropsychological Test of Executive Functioning 2
Time Frame: Change from Baseline in Executive Functioning at 3 Weeks
|
Computerized Stroop Test
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Change from Baseline in Executive Functioning at 3 Weeks
|
Neuropsychological Tests of Visual Working Memory
Time Frame: Change from Baseline in Visual Working Memory at 3 Weeks
|
Benton Visual Retention Test Form F&G (a test of visual working memory)
|
Change from Baseline in Visual Working Memory at 3 Weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Suzanne Craft, PhD, VA Puget Sound Health Care System; University of Washington School of Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Cognition Disorders
- Alzheimer Disease
- Cognitive Dysfunction
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Insulin
- Insulin, Globin Zinc
- Insulin Detemir
Other Study ID Numbers
- 39683-A
- 2P50AG005136-27 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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