The SNIFF 3-Week Aptar Device study will involve using a device to administer insulin or placebo through each participant's nose or intra-nasally. Insulin is a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. This study is measuring how much insulin the device delivers. In addition, this study will look at the effects of insulin or placebo administered intra-nasally using an intranasal delivery device on memory, blood, and cerebrospinal fluid (CSF).
The proposed study will examine whether an intranasal delivery device can be used by adults with preclinical Alzheimer's disease (cognitively normal but with abnormal brain levels of the hallmark peptide Aβ) to reliably deliver insulin or placebo four times daily over a 4 week period. We will also examine effects of treatment on cognition, CSF biomarkers, and cerebral perfusion. If successful, information gained from the study will inform the design of future Phase III trials of intranasal insulin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Participants will administer 40 IU of Humulin® U-100 insulin four times per day with an intranasal delivery device.
Participants will administer placebo (insulin diluent) four times per day with an intranasal delivery device.
Participants will be assigned to receive Humulin® insulin or placebo administered through the Aptar Pharma CPS intranasal delivery device.
Percentage of Prescribed Dose Taken
Participant self-reported medication adherence information will be calculated by study staff on a 0%-100% scale. A score below 80% indicates low medication adherence and a score of 80% or higher indicates high medication adherence.
Time frame: Week 4
Change in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) Z-Score
Cognition will be measured using the PACC5 scale, which includes the free/cued selective reminding test, delayed paragraph recall, digit-symbol substitution, mini mental state score, and the category fluency task. The PACC5 is a composite score comprised of measures of global cognition, memory, and executive function. The score reflects an averaged z-score, with higher scores indicating better cognitive performance.
Time frame: Baseline to Week 8
Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog 14) Score
A psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 65 (worse), and are added to the mean of the words not immediately recalled (max of 10) and the number of items not recalled after a delay (ranging from 0-10) all total the maximum score of 85. A positive change indicates cognitive worsening.
Time frame: Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Insulin Levels
Measurement of the levels of insulin in cerebrospinal fluid (CSF) after being delivered with the intranasal delivery device. This will help to determine the ability of the intranasal delivery device to increase levels of insulin in CSF.
Time frame: Baseline to Week 8
Change in amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)
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Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 40. CSF Aβ40 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.
Time frame: Baseline to Week 8
Change in amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)
Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 42. CSF Aβ42 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.
Time frame: Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau
Cerebrospinal fluid (CSF) samples will be used to measure the levels of total tau protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Time frame: Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181
Cerebrospinal fluid (CSF) samples will be used to measure the levels of phospho-tau 181 protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Time frame: Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 217
Cerebrospinal fluid (CSF) samples will be used to measure the levels of phospho-tau 217 protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Time frame: Baseline to Week 8