Measurement of Insulin Levels in Cerebral Spinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose (INI-CSF)

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 mild cognitive impairment and dementia, but more evidence is needed to support the ability to effectively target the brain through intranasal routes.

12 healthy adults will be randomly assigned to receive a single dose of either 40 units ("low dose" group) or 80 units ("high dose" group) of insulin. Participants will undergo image-guided lumbar puncture (spinal tap) performed by a study radiologist. 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 the SipNose device to effectively deliver insulin to the central nervous system of humans as measured in the cerebrospinal fluid.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Low dose Regular Insulin; Drug: High dose Regular insulin

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Meghan E O'Brien; Phone Number: 651-495-6363; Email: Meghan.E.Obrien@HealthPartners.com

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • Recruiting
      • HealthPartners Neuroscience Center
      • Contact: Clinical Trial Coordinator; Phone Number: 651-495-6363

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subject is between ≥18 and ≤ 35 years of age
2. Subject's body mass index is between >=18.5 and <=24.9
3. Subject must be proficient in speaking English to comply with instructions and measures for the study
4. Subject can provide written informed consent
5. Female subjects must have either: (1) a negative pregnancy test at the screening and treatment visits 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose Intranasal Insulin; One dose of 40 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device.	Drug: Low dose Regular Insulin; Regular insulin administered intranasally at either 40 IU; Other Names: Novolin-R
Experimental: High dose Intranasal Insulin; One dose of 80 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device.	Drug: High dose Regular insulin; Regular insulin administered intranasally at either 80 IU; Other Names: Novolin-R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Concentration 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
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 as 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. Serum insulin concentration will also be reported by Cmax (peak concentration), Tmax (time of peak concentration), and AUC (area under the curve, measured as time x concentration).	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 administration
Tmax of insulin concentration - Serum	Serum 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 - 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

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Investigators: Principal Investigator: Leah R Hanson, PhD, HealthPartners Neuroscience Research

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: A21-299

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