SNIFF - 3-Week Aptar CPS Device
- Conditions
- Alzheimer Disease, Early OnsetMild Cognitive ImpairmentCognitive Impairment
- Interventions
- Registration Number
- NCT05006599
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 40
- Age 55 to 85 (inclusive)
- Fluent in English
- Cognitively normal or diagnosis of amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD)
- Amyloid positive by positron emission tomography (PET) or cerebrospinal fluid (CSF) criteria
- Stable medical condition for 3 months prior to screening visit
- Stable medications for 4 weeks prior to the screening and study visits (exceptions may be made on a case by case basis by the study physician)
- Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician
- A diagnosis of dementia other than Alzheimer's disease (AD)
- History of a clinically significant stroke
- Current evidence or history in past two years of epilepsy, head injury with loss of consciousness, any major psychiatric disorder including psychosis, major depression, bipolar disorder
- Diabetes (type I or type II) insulin-dependent and non-insulin-dependent diabetes mellitus
- Current or past regular use of insulin or any other anti-diabetic medication within 2 months of screening visit
- History of seizure within past five years
- Pregnancy or possible pregnancy
- Use of anticoagulants
- Residence in a skilled nursing facility at screening
- Use of an investigational agent within two months of screening visit
- Regular use of alcohol, narcotics, anticonvulsants, anti-parkinsonian medications, or any other exclusionary medications (exceptions may be made on a case by case basis by the study physician)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Humulin® R U-100 Insulin (Humulin® R U-100) Twenty randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive intranasal administrations of Humulin® R U-100 (40 IU) four times daily for 3 weeks. Humulin® R U-100 Aptar Pharma CPS Intranasal Delivery Device Twenty randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive intranasal administrations of Humulin® R U-100 (40 IU) four times daily for 3 weeks. Placebo Aptar Pharma CPS Intranasal Delivery Device Twenty randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive intranasal administrations of placebo (insulin diluent) four times daily for 3 weeks. Placebo Placebo Twenty randomly assigned participants with Alzheimer's disease or mild cognitive impairment will receive intranasal administrations of placebo (insulin diluent) four times daily for 3 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Prescribed Dose Taken Week 4 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.
- Secondary Outcome Measures
Name Time Method Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181 Baseline to Week 8 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.
Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog 14) Score Baseline to Week 8 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.
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau Baseline to Week 8 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.
Change in amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF) Baseline to Week 8 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.
Change in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) Z-Score Baseline to Week 8 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.
Change in Cerebrospinal Fluid (CSF) Insulin Levels Baseline to Week 8 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.
Change in amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF) Baseline to Week 8 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.
Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 217 Baseline to Week 8 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.