Measurement of Insulin Levels in the Cerebrospinal Fluid of Healthy Adults After a Single Intranasal Dose - Middle Age (INI-CSF-MA)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Drug: Low Dose Regular insulin; Drug: High Dose Regular insulin; Other: 0.9% Saline

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • HealthPartners Neuroscience Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose intranasal insulin; One dose of 40 international units of regular insulin administered intranasally.	Drug: Low Dose Regular insulin; Administered intranasally at 40 IU; Other Names: Novolin-R
Experimental: High dose Intranasal Insulin; One dose of 80 international units of regular insulin administered intranasally.	Drug: High Dose Regular insulin; Administered Intranasally at 80 IU; Other Names: Novolin-R
Placebo Comparator: Placebo Control; One dose of 0.9% saline administered intranasally.	Other: 0.9% Saline; Placebo control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of insulin over Time - Cerebrospinal fluid	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.	0-40 minutes post-intranasal administration
Cmax of insulin concentration- Cerebrospinal Fluid	CSF insulin concentration will also be reported by Cmax (peak concentration)	0-40 minutes post- intranasal administration
Tmax of insulin concentration-Cerebrospinal FLuid	CSF insulin concentration will also be reported by Tmax (time of peak concentration)	0-40 minutes post-intranasal administration
AUC (area under the curve) of insulin concentration-Cerebrospinal Fluid	CSF insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration)	0-40 minutes post-intranasal administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (area under the curve) of insulin concentration - Serum	Serum insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration).	0-40 minutes post-intranasal administration
Insulin Concentration Over Time- Serum	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.	0-40 minutes post-intranasal administration
Cmax of insulin concentration - Serum	Serum insulin concentration will also be reported by Cmax (peak concentration)	0-40 minutes post-intranasal adminitration
Tmax of insulin - Serum	Serum insulin concentration will also be reported by Tmax (time to peak concentration)	0-40 minutes post-intranasal administration

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Collaborators: Uniformed Services University of the Health Sciences; Department of Defense Congressionally Directed Medical Research Program
• Investigators: Principal Investigator: Leah R Hanson, PhD, HealthPartners Institute; Principal Investigator: Kimberly Byrnes, PhD, Uniformed Services University of the Health Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): August 30, 2025
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: May 23, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: intranasal; insulin; Healthy Adults; Middle Age
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Nutritional and Metabolic Diseases; Insulin Resistance; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Insulins; Pancreatic Hormones; Proinsulin; Insulin; Saline Solution
• Other Study ID Numbers: A22-210; CDMRP-SC220220 (Other Identifier: Department of Defense Congressionally Directed Medical Research Program)

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: No