SNIFF - Combo INI+EMPA Trial

Wake Forest University (WFU)

Status and phase: Completed; Phase 2

Conditions: Alzheimer Disease; Cognitive Impairment; Mild Cognitive Impairment

Treatments: Drug: Insulin (Humulin® R U-100); Drug: Placebo (Insulin Diluent); Drug: Empagliflozin 10 MG; Drug: Placebo (Capsules); Device: Aptar Pharma CPS Intranasal Delivery Device

Study type: Interventional

Funder types: Other

Identifiers

NCT05081219

IRB00075245

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 55 to 85 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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30 participants in 4 patient groups, including a placebo group

Intranasal Insulin and Empagliflozin Placebo

Experimental group

Description:

* 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

Treatment:

Device: Aptar Pharma CPS Intranasal Delivery Device

Drug: Placebo (Capsules)

Drug: Insulin (Humulin® R U-100)

Empagliflozin and Intranasal Insulin Placebo

Experimental group

Description:

* 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

Treatment:

Device: Aptar Pharma CPS Intranasal Delivery Device

Drug: Placebo (Insulin Diluent)

Drug: Empagliflozin 10 MG

Intranasal Insulin and Empagliflozin

Experimental group

Description:

* 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

Treatment:

Device: Aptar Pharma CPS Intranasal Delivery Device

Drug: Empagliflozin 10 MG

Drug: Insulin (Humulin® R U-100)

Placebo

Placebo Comparator group

Description:

* 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

Treatment:

Device: Aptar Pharma CPS Intranasal Delivery Device

Drug: Placebo (Capsules)

Drug: Placebo (Insulin Diluent)