## Protocol Section
### Identification Module
**NCT ID:** NCT06434038

**Acronym:** INI-CSF-MA

**Brief Title:** Measurement of Insulin Levels in the Cerebrospinal Fluid of Healthy Adults After a Single Intranasal Dose - Middle Age

**Official Title:** Measurement of Insulin Levels in the Cerebrospinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose - Middle Age

#### Organization Study ID Info
**ID:** A22-210
#### Organization
**Class:** OTHER
**Full Name:** HealthPartners Institute
#### Secondary ID Infos
**Domain:** Department of Defense
**ID:** CDMRP-SC220220
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-02-28

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-02-28

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-10-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-23
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Collaborators

**Class:** FED

**Name:** Uniformed Services University of the Health Sciences

**Class:** FED

**Name:** United States Department of Defense

#### Lead Sponsor

**Class:** OTHER

**Name:** HealthPartners Institute

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to find out whether insulin, a drug approved by the FDA for the treatment of diabetes mellitus, reaches the brain and spinal cord when delivered as a nasal spray (intranasally). Intranasal insulin has been shown to improve memory and mood in patients with neurological diseases such as mild cognitive impairment and dementia, but more evidence is needed to support the ability to effectively target the brain through intranasal routes.

18 healthy middle-aged adults will be randomly assigned to receive a single intranasal dose of 40 units insulin ("low dose" group), 80 units insulin ("high dose" group), or saline (placebo, or control group). Participants will undergo an image-guided lumbar puncture (spinal tap) performed by a study clinician. Samples of cerebrospinal fluid (a fluid surrounding the brain and spinal cord) and blood will be collected at 5 timepoints during the lumbar puncture: once prior to the administration of intranasal insulin, and again at 10, 20, 30, and 40 minutes after the dose is given. Samples will be tested to determine the level of insulin detected in the cerebrospinal fluid and blood at each time point. Results of this study will provide essential information about the ability of insulin to reach the brain after intranasal administration.

### Conditions Module

**Conditions:**

- Healthy

**Keywords:**

- insulin

- intranasal

- Healthy Adults

- Middle Age

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Participants will be randomized into one of 3 groups: 40 IU insulin, 80 IU insulin, or saline control.

##### Masking Info

**Masking:** SINGLE

**Masking Description:** Single-blind

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 18

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** One dose of 40 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device.

**Intervention Names:**

- Drug: Low Dose Regular insulin

**Label:** Low dose intranasal insulin

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** One dose of 80 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device.

**Intervention Names:**

- Drug: High Dose Regular insulin

**Label:** High dose Intranasal Insulin

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** One dose of 0.9% saline administered intranasally using the SipNose SP1N1C1 device

**Intervention Names:**

- Other: 0.9% Saline

**Label:** Placebo Control

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Low dose intranasal insulin

**Description:** Administered intranasally at 40 IU

**Name:** Low Dose Regular insulin

**Other Names:**

- Novolin-R

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- High dose Intranasal Insulin

**Description:** Administered Intranasally at 80 IU

**Name:** High Dose Regular insulin

**Other Names:**

- Novolin-R

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Placebo Control

**Description:** Placebo control

**Name:** 0.9% Saline

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Insulin concentration detected in cerebrospinal fluid at 5 time points (pre-insulin dose; and 10, 20, 30, 40 minutes after dose). Values will be reported as μIU/mL. Higher values indicate a greater concentration of insulin in the cerebrospinal fluid. Concentrations for each time point (overall and by dose) will be reported as a mean +/- standard error.

**Measure:** Concentration of insulin over Time - Cerebrospinal fluid

**Time Frame:** 0-40 minutes post-intranasal administration

**Description:** CSF insulin concentration will also be reported by Cmax (peak concentration)

**Measure:** Cmax of insulin concentration- Cerebrospinal Fluid

**Time Frame:** 0-40 minutes post- intranasal administration

**Description:** CSF insulin concentration will also be reported by Tmax (time of peak concentration)

**Measure:** Tmax of insulin concentration-Cerebrospinal FLuid

**Time Frame:** 0-40 minutes post-intranasal administration

**Description:** CSF insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration)

**Measure:** AUC (area under the curve) of insulin concentration-Cerebrospinal Fluid

**Time Frame:** 0-40 minutes post-intranasal administration

#### Secondary Outcomes

**Description:** Insulin concentration detected in blood at 5 time points (pre-insulin dose; and 10, 20, 30, 40 minutes after dose). Values will be reported at μIU/mL. Higher values indicate a greater concentration of insulin in the blood. Concentrations for each time point (overall and by dose) will be reported as a mean +/- standard error.

**Measure:** Insulin Concentration Over Time- Serum

**Time Frame:** 0-40 minutes post-intranasal administration

**Description:** Serum insulin concentration will also be reported by Cmax (peak concentration)

**Measure:** Cmax of insulin concentration - Serum

**Time Frame:** 0-40 minutes post-intranasal adminitration

**Description:** Serum insulin concentration will also be reported by Tmax (time to peak concentration)

**Measure:** Tmax of insulin - Serum

**Time Frame:** 0-40 minutes post-intranasal administration

**Description:** Serum insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration).

**Measure:** AUC (area under the curve) of insulin concentration - Serum

**Time Frame:** 0-40 minutes post-intranasal administration

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Subject is between ≥36 and ≤ 55 years of age
2. Subject's BMI is between \>=18.5 and \<=24.9, or can safely undergo a lumbar puncture at the discretion of the radiologist
3. MOCA score ≥26
4. Subject must be proficient in speaking English to comply with instructions and measures for the study
5. Subject can provide written informed consent
6. Female subjects must have either: (1) a negative pregnancy test at the screening visit and treatment visit OR (2) be at least 2 years post-menopausal / surgically sterile.

Exclusion Criteria:

1. Subject has medical history and/or clinically determined disorders: chronic sinusitis, previous nasal and/or oto-pharyngeal surgery and severe deviated septum and/or other anomalies.
2. Subject has history of any of the following: active and significant central nervous system, psychiatric illness, pulmonary, or cardiovascular disorders or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator
3. Subject has participated in a clinical trial investigation within 3 months of this study.
4. Subject has an insulin allergy
5. Subject has Insulin-dependent diabetes
6. Subject is pregnant or breast feeding
7. Contraindication to spinal tap or other safety factors that preclude lumbar puncture in the investigator's opinion
8. Any other clinically relevant finding that would pose a safety risk to the subject as determined by the investigator

**Healthy Volunteers:** True

**Maximum Age:** 55 Years

**Minimum Age:** 36 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Meghan.E.Obrien@HealthPartners.com

**Name:** Meghan E O'Brien

**Phone:** 651-495-6363

**Role:** CONTACT

**Contact 2:**

**Email:** Bethany.K.Crouse@HealthPartners.com

**Name:** Bethany K Crouse, PhD

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Saint Paul

**Contacts:**

***Contact 1:***

- **Email:** Meghan.E.Obrien@HealthPartners.com

- **Name:** Meghan E O'Brien

- **Role:** CONTACT

***Contact 2:***

- **Email:** Bethany.K.Crouse@HealthPartners.com

- **Name:** Bethany K Crouse, PhD

- **Role:** CONTACT

***Contact 3:***

- **Name:** Leah R Hanson, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** HealthPartners Neuroscience Center

**State:** Minnesota

**Zip:** 55130

#### Overall Officials

**Official 1:**

**Affiliation:** HealthPartners Institute

**Name:** Leah R Hanson, PhD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Uniformed Services University of the Health Sciences

**Name:** Kimberly Byrnes, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Intervention Browse Module - Ancestors

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: HIGH

- As Found: Day 1

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: HIGH

- As Found: Premenopausal

- ID: M17768

- Name: Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000007328

- Term: Insulin

- ID: C000557859

- Term: Insulin, Globin Zinc

### Misc Info Module

- Version Holder: 2024-05-31
