SNIFF - Combo INI+EMPA Trial

October 11, 2023 updated by: Wake Forest University Health Sciences

Study of Nasal Insulin to Fight Forgetfulness - Combination Intranasal Insulin and Empagliflozin Trial

The proposed pilot study will provide safety and efficacy preliminary data regarding singular and combined effects of two therapeutic approaches, intranasal insulin and treatment with the sodium-glucose cotransporter type 2 inhibitor (SGLT2i) empagliflozin, to correct bioenergetic and vascular dysfunction in adults with preclinical Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) or early AD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will consist of a single site, randomized, double-blind trial comparing the effects of 4 weeks of intranasal insulin(40 International Units four times daily), empagliflozin (10 mg daily) and combined intranasal insulin (INI) and empagliflozin (empa) compared with placebo on cerebrospinal fluid (CSF) biomarkers and cognition.

At study entry, participants will be randomized to one of 4 conditions: INI, empa, INI+empa or placebo. Participants who are cognitively normal but have abnormal elevations of brain amyloid or who have mild cognitive impairment (MCI) or early Alzheimer's disease (AD) will be enrolled.

The primary outcome measure will consist of safety (treatment-related serious adverse events). Secondary outcome measures will consist of cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral blood flow.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences / Wake Forest School of Medicine
        • Contact:
        • Principal Investigator:
          • Suzanne Craft, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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, unless documentation received from prescribing clinician that anticoagulant medication can be held before LP, and approved by study clinician
  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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Experimental: Intranasal Insulin and Empagliflozin Placebo
  • 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
  • Placebo capsules taken by mouth 30 minutes before breakfast once daily
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.
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.
Drug: Placebo (Capsules)
Participants will be assigned to receive placebo capsules (Empagliflozin 10 mg) to be taken by mouth once daily.
Experimental: Empagliflozin and Intranasal Insulin Placebo
  • Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
  • 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
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.
Drug: Empagliflozin 10 MG
Participants will be assigned to receive Empagliflozin 10 mg capsules to be taken by mouth once daily.
Drug: Placebo (Insulin Diluent)
Participants will administer placebo (insulin diluent) four times per day with an intranasal delivery device.
Experimental: Intranasal Insulin and Empagliflozin
  • 40 IU of intranasal insulin administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
  • Empagliflozin 10 mg capsules taken by mouth 30 minutes before breakfast once daily
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.
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.
Drug: Empagliflozin 10 MG
Participants will be assigned to receive Empagliflozin 10 mg capsules to be taken by mouth once daily.
Placebo Comparator: Placebo
  • 40 IU of intranasal insulin diluent (placebo) administered using the Aptar CPS device 30 minutes prior to eating and 30 minutes before bedtime for a total of four (4) times daily
  • Placebo capsules taken by mouth 30 minutes before breakfast once daily
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.
Drug: Placebo (Capsules)
Participants will be assigned to receive placebo capsules (Empagliflozin 10 mg) to be taken by mouth once daily.
Drug: Placebo (Insulin Diluent)
Participants will administer placebo (insulin diluent) four times per day with an intranasal delivery device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Treatment-related Serious Adverse Events as Assessed by CTCAE v5.0
Time Frame: Week 8
Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE v5.0). The number of participants with grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment will be reported.
Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) Z-Score
Time Frame: 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.
Baseline to Week 8
Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog 14) Score
Time Frame: 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.
Baseline to Week 8
Change in amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)
Time Frame: 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.
Baseline to Week 8
Change in amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)
Time Frame: 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.
Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau
Time Frame: 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.
Baseline to Week 8
Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181
Time Frame: 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.
Baseline to Week 8
Change in Total Cerebral Blood Flow (CBF) Using MRI Pseudocontinuous Arterial Spin Labeling (ASL)
Time Frame: Baseline to Week 8
Change in CBF in mL/100g/min, calculated as the difference between the pre- and post- ASL flow in response to the study intervention.
Baseline to Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Investigators

  • Principal Investigator: Suzanne Craft, PhD, Wake Forest University Health Sciences / Wake Forest School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 14, 2021

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

October 4, 2021

First Submitted That Met QC Criteria

October 4, 2021

First Posted (Actual)

October 18, 2021

Study Record Updates

Last Update Posted (Actual)

October 13, 2023

Last Update Submitted That Met QC Criteria

October 11, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00075245

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

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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