Healthy
Conditions
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 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.
Interventions
Regular insulin administered intranasally at either 40 IU
Regular insulin administered intranasally at either 80 IU
Sponsors
HealthPartners Institute
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
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). |
| Insulin Concentration 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 deviation. The limit of detection of the assay was 0.15mU/L (0.0065µg/L). |
| 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 |
|---|---|---|
| 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 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 deviation. 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). |
| Cmax of Insulin Concentration - Serum | 0-40 minutes post-intranasal administration | Serum insulin concentration will also be reported by Cmax (peak concentration). |
| Tmax of Insulin Concentration - Serum | 0-40 minutes post-intranasal administration | Serum insulin concentration will also be reported by Tmax (time of 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
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Intranasal Insulin One dose of 40 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device.
Low dose Regular Insulin: Regular insulin administered intranasally at either 40 IU | 2 |
| High Dose Intranasal Insulin One dose of 80 international units of regular insulin administered intranasally using the SipNose SP1N1C1 device.
High dose Regular insulin: Regular insulin administered intranasally at either 80 IU | 0 |
| Total | 2 |
Baseline characteristics
| Characteristic | Low Dose Intranasal Insulin | High Dose Intranasal Insulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Sex/Gender, Customized Sex assigned at birth Female | 2 Participants | 0 Participants | 2 Participants |
| Sex/Gender, Customized Sex assigned at birth Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 0 |
| other Total, other adverse events | 2 / 2 | 0 / 0 |
| serious Total, serious adverse events | 1 / 2 | 0 / 0 |
Outcome results
Primary
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).
Time frame: 0-40 minutes post-intranasal administration
Population: AUC was not calculated as most values were below the limit of detection of the assay.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low dose Intranasal Insulin | AUC (Area Under the Curve) of Insulin Concentration - Cerebrospinal Fluid | NA uU*min/mL |
Primary
Cmax of Insulin Concentration - Cerebrospinal Fluid
CSF insulin concentration will also be reported by Cmax (peak concentration)
Time frame: 0-40 minutes post-intranasal administration
Population: Cmax was not summarized as most values were below the limit of detection of the assay.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low dose Intranasal Insulin | Cmax of Insulin Concentration - Cerebrospinal Fluid | NA uU/mL |
Primary
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 deviation. The limit of detection of the assay was 0.15mU/L (0.0065µg/L).
Time frame: 0-40 minutes post-intranasal administration
Population: Study was terminated. No high dose individuals were consented prior to termination.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Cerebrospinal Fluid | 0 minutes | 0.57 µU/ml | Standard Deviation 0.64 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Cerebrospinal Fluid | 10 minutes | 0.01 µU/ml | Standard Deviation 0.01 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Cerebrospinal Fluid | 20 minutes | 0.02 µU/ml | Standard Deviation 0.03 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Cerebrospinal Fluid | 30 minutes | 0.05 µU/ml | Standard Deviation 0.04 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Cerebrospinal Fluid | 40 minutes | 0 µU/ml | Standard Deviation 0 |
Primary
Tmax of Insulin Concentration - Cerebrospinal Fluid
CSF insulin concentration will also be reported by Tmax (time of peak concentration)
Time frame: 0-40 minutes post-intranasal administration
Population: Tmax was not calculated as most values were below the limit of detection of the assay.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low dose Intranasal Insulin | Tmax of Insulin Concentration - Cerebrospinal Fluid | NA minutes |
Secondary
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).
Time frame: 0-40 minutes post-intranasal administration
Population: Study was closed. No high dose individuals were consented prior to closure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low dose Intranasal Insulin | AUC (Area Under the Curve) of Insulin Concentration - Serum | 382.25 uU*min/ml | Standard Deviation 115.75 |
Secondary
Cmax of Insulin Concentration - Serum
Serum insulin concentration will also be reported by Cmax (peak concentration).
Time frame: 0-40 minutes post-intranasal administration
Population: Study was closed. No high dose individuals were consented prior to closure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low dose Intranasal Insulin | Cmax of Insulin Concentration - Serum | 10.85 uU/ml | Standard Deviation 3.35 |
Secondary
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 deviation. 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).
Time frame: 0-40 minutes post-intranasal administration
Population: Study was closed. No high dose individuals were consented prior to closure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Serum | 0 minutes | 5.8 µU/ml | Standard Deviation 0.85 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Serum | 10 minute | 10.8 µU/ml | Standard Deviation 4.8 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Serum | 20 minutes | 9.75 µU/ml | Standard Deviation 3.6 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Serum | 30 minutes | 9.75 µU/ml | Standard Deviation 5.16 |
| Low dose Intranasal Insulin | Insulin Concentration Over Time - Serum | 40 minutes | 9.95 µU/ml | Standard Deviation 8.88 |
Secondary
Tmax of Insulin Concentration - Serum
Serum insulin concentration will also be reported by Tmax (time of peak concentration).
Time frame: 0-40 minutes post-intranasal administration
Population: Study was closed. No high dose individuals were consented prior to closure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low dose Intranasal Insulin | Tmax of Insulin Concentration - Serum | 10.0 minutes | Standard Deviation 0 |