Healthy
Conditions
Keywords
insulin, intranasal, Healthy Adults, Middle Age
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.
Interventions
Administered intranasally at 40 IU
Administered Intranasally at 80 IU
OTHER0.9% Saline
Placebo control
Sponsors
Uniformed Services University of the Health Sciences
Department of Defense Congressionally Directed Medical Research Program
HealthPartners Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Masking description
Single-blind
Intervention model description
Participants will be randomized into one of 3 groups: 40 IU insulin, 80 IU insulin, or saline control.
Eligibility
Sex/Gender
ALL
Age
36 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC (area under the curve) of insulin concentration-Cerebrospinal Fluid | 0-40 minutes post-intranasal administration | CSF insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration) |
| Concentration of insulin over Time - Cerebrospinal fluid | 0-40 minutes post-intranasal administration | 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. |
| Cmax of insulin concentration- Cerebrospinal Fluid | 0-40 minutes post- intranasal administration | CSF insulin concentration will also be reported by Cmax (peak concentration) |
| Tmax of insulin concentration-Cerebrospinal FLuid | 0-40 minutes post-intranasal administration | CSF insulin concentration will also be reported by Tmax (time of peak concentration) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax of insulin - Serum | 0-40 minutes post-intranasal administration | Serum insulin concentration will also be reported by Tmax (time to peak concentration) |
| Insulin Concentration Over Time- Serum | 0-40 minutes post-intranasal administration | 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. |
| Cmax of insulin concentration - Serum | 0-40 minutes post-intranasal adminitration | Serum insulin concentration will also be reported by Cmax (peak concentration) |
| AUC (area under the curve) of insulin concentration - Serum | 0-40 minutes post-intranasal administration | Serum insulin concentration will also be reported by AUC (area under the curve, measured as time x concentration). |
Countries
United States
Outcome results
None listed