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

NCT06434038 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: A22-210CDMRP-SC220220
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Healthy

Keywords

insulin; intranasal; Healthy Adults; Middle Age

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Insulin Concentration Over Time- Serum

  0-40 minutes post-intranasal administration

• Cmax of insulin concentration - Serum

  0-40 minutes post-intranasal adminitration

• Tmax of insulin - Serum

  0-40 minutes post-intranasal administration

• AUC (area under the curve) of insulin concentration - Serum

  0-40 minutes post-intranasal administration

Study Arms (3)

Low dose intranasal insulin

EXPERIMENTAL

One dose of 40 international units of regular insulin administered intranasally.

Drug: Low Dose Regular insulin

High dose Intranasal Insulin

EXPERIMENTAL

One dose of 80 international units of regular insulin administered intranasally.

Drug: High Dose Regular insulin

Placebo Control

PLACEBO COMPARATOR

One dose of 0.9% saline administered intranasally.

Other: 0.9% Saline

Interventions

Low Dose Regular insulin DRUG

Administered intranasally at 40 IU

Also known as: Novolin-R

Low dose intranasal insulin

High Dose Regular insulin DRUG

Administered Intranasally at 80 IU

Also known as: Novolin-R

High dose Intranasal Insulin

0.9% Saline OTHER

Placebo control

Placebo Control

Eligibility Criteria

• Age: 36 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is between ≥36 and ≤ 55 years of age
• Subject's BMI is between \>=18.5 and \<=24.9, or can safely undergo a lumbar puncture at the discretion of the radiologist
• MOCA score ≥26
• Subject must be proficient in speaking English to comply with instructions and measures for the study
• Subject can provide written informed consent
• 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.

You may not qualify if:

• 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.
• Subject has participated in a clinical trial investigation within 3 months of this study.
• Subject has an insulin allergy
• Subject has Insulin-dependent diabetes
• Subject is pregnant or breast feeding
• Contraindication to spinal tap or other safety factors that preclude lumbar puncture in the investigator's opinion
• Any other clinically relevant finding that would pose a safety risk to the subject as determined by the investigator

Sponsors & Collaborators

• HealthPartners Institute: lead
• Uniformed Services University of the Health Sciences: collaborator
• Department of Defense Congressionally Directed Medical Research Program: collaborator

Study Sites (1)

HealthPartners Neuroscience Center

Saint Paul, Minnesota, 55130, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Insulin; Saline Solution

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Leah R Hanson, PhD

  HealthPartners Institute

  PRINCIPAL INVESTIGATOR

• Kimberly Byrnes, PhD

  Uniformed Services University of the Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single-blind
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: May 30, 2024
• Study Start: August 30, 2025
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)