SNIFF - 3-Week Aptar CPS Device

Mild Cognitive Impairment Clinical Trial

Official title:

Study of Nasal Insulin to Fight Forgetfulness (SNIFF) - 3-Week Aptar CPS Device

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05006599
• Other study ID #: IRB00073876
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2025
• Est. completion date: May 2031

Study information

• Verified date: April 2024
• Source: Wake Forest University Health Sciences
• Contact: Deborah Dahl, RN
• Phone: 336-713-3432
• Email: ddahl[@]wakehealth.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: May 2031
• Est. primary completion date: May 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Age 55 to 85 (inclusive)

2. Fluent in English

3. Cognitively normal or diagnosis of amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD)

4. Amyloid positive by positron emission tomography (PET) or cerebrospinal fluid (CSF) criteria

5. Stable medical condition for 3 months prior to screening visit

6. 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)

7. Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician

Exclusion Criteria:

1. A diagnosis of dementia other than Alzheimer's disease (AD)

2. History of a clinically significant stroke

3. 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

4. Diabetes (type I or type II) insulin-dependent and non-insulin-dependent diabetes mellitus

5. Current or past regular use of insulin or any other anti-diabetic medication within 2 months of screening visit

6. History of seizure within past five years

7. Pregnancy or possible pregnancy

8. Use of anticoagulants

9. Residence in a skilled nursing facility at screening

10. Use of an investigational agent within two months of screening visit

11. 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)

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Early Onset
• Cognitive Dysfunction
• Cognitive Impairment
• Mild Cognitive Impairment

Intervention

Drug:
• Insulin (Humulin® R U-100)
Participants will administer 40 IU of Humulin® U-100 insulin four times per day with an intranasal delivery device.
• Placebo
Participants will administer placebo (insulin diluent) four times per day with an intranasal delivery device.

Device:
• Aptar Pharma CPS Intranasal Delivery Device
Participants will be assigned to receive Humulin® insulin or placebo administered through the Aptar Pharma CPS intranasal delivery device.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

References & Publications (52)

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* Note: There are 52 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Quick Dementia Rating Scale (QDRS) Score	The QDRS (Galvin, 2015) is a clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (Clinical Dementia Rating score of 0, 0.5, 1, 2, or 3, respectively). The score assesses six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. At Screening the QDRS global score will be used for eligibility purposes. For all other administrations, the 6 domain scores will be summed to get the QDRS Sum of Boxes (SB) score. Sum of boxes score ranges from 0-100 with a high score meaning more severe dementia.	Baseline to Week 8
Other	Change in Patient Health Questionnaire (PHQ-9) Score	The Patient Health Questionnaire (PHQ-9) is a 9-item, validated measure of depression severity. Respondents indicate how bothered by problems they are on a scale from 0 (not at all) to 3 (nearly every day). Total scores range from 0 to 27, where higher scores indicate more severe depression.	Baseline to Week 8
Other	Change in Generalized Anxiety Disorder scale-7 (GAD-7) Score	Changes in anxiety will be measured using the Generalized Anxiety Disorder Scale (GAD-7), which contains 7 items with total scores ranging from 0 to 21. Scores of 5, 10, and 15 are cut-offs for mild, moderate, and severe anxiety, respectively.	Baseline to Week 8
Other	Change in PROMIS Sleep Disturbance Questionnaire Score	A questionnaire to assess self-reported quality of general sleep and sleep disturbance. Each item on the form is rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 8 to 40 with higher scores indicating greater severity of sleep disturbance.	Baseline to Week 8
Other	Change in the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-ADL-MCI)	An interview-based assessment of information provided by the study partner (informant). The total scores based on 18 items on the scale range from 0 to 53 with lower scores representing greater impairment.	Baseline to Week 8
Primary	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.	Week 4
Secondary	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.	Baseline to Week 8
Secondary	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.	Baseline to Week 8
Secondary	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.	Baseline to Week 8
Secondary	Change in amyloid ß-peptide (Aß) 40 (Aß40) in Cerebrospinal Fluid (CSF)	Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid ß-peptide (Aß) 40. CSF Aß40 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.	Baseline to Week 8
Secondary	Change in amyloid ß-peptide (Aß) 42 (Aß42) in Cerebrospinal Fluid (CSF)	Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid ß-peptide (Aß) 42. CSF Aß42 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.	Baseline to Week 8
Secondary	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.	Baseline to Week 8
Secondary	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.	Baseline to Week 8
Secondary	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.	Baseline to Week 8