Safety and Efficacy of Combining Intranasal Insulin & Acute Exercise

Study Overview
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Brief Summary
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To determine if physical activity engagement alters the dose-response profile and safety of administration of insulin into the intranasal mucosa.

Detailed Description
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Using a randomized placebo controlled double-blind pre-posttest design, participants will be randomly assigned to receive a dose of either 0, 20, 40, 60, 80, 100, or 120 IU of NovoLog insulin aspart prior to being randomized into participating in a 20 minute session of either moderate-intensity aerobic exercise or a passive control condition. The efficacy of the intranasal insulin for inducing alterations in cognition will be assessed using both behavioral and neuroelectric measures. The safety of the protocol will be assessed using a symptom questionnaire assessing common symptoms of altered blood glucose and common side effects of intranasal insulin.

Official Title
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Placebo Controlled Phase II Clinical Trial: Safety and Efficacy of Combining Intranasal Insulin & Acute Exercise

Conditions
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Insulin, Exercise

Intervention / Treatment
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* Drug: Placebo into the intranasal mucosa
* Drug: 20 IU NovoLog Insulin aspart into the intranasal mucosa
* Drug: 40 IU NovoLog Insulin aspart into the intranasal mucosa
* Drug: 60 IU NovoLog Insulin aspart into the intranasal mucosa
* Drug: 80 IU NovoLog Insulin aspart into the intranasal mucosa
* Drug: 100 IU NovoLog Insulin aspart into the intranasal mucosa
* Drug: 120 IU NovoLog Insulin aspart into the intranasal mucosa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be over the age of 18.. Participants must have normal or corrected-to-normal vision in order to complete the cognitive task. Exclusion Criteria: Lack of consent. Presence of any major neurological health issues, brain trauma, or concussion with loss of consciousness assessed through a health history and demographics questionnaire. Type I or Type II Diabetes Self-reported pregnancy Currently has any type of inflammation or blockage of the nasal passageways (i.e. allergies or a cold affecting the sinuses).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Random allocation to a dose of intranasal insulin (0, 20, 40, 60, 80, 100, 120) Within each dose, random allocation to exercise or control activity.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Passive Control<br>20 minute sedentary control period during which participants watched an emotionally neutral video. | Drug: Placebo into the intranasal mucosa<br>* 6 doses of 0.2mL saline solution administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: Saline;Drug: 20 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 5 doses of 0.2mL saline solution, 1 dose of 0.2mL NovoLog Insulin aspart (20 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 40 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 4 doses of 0.2mL saline solution, 2 doses of 0.2mL NovoLog Insulin aspart (40 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 60 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 3 doses of 0.2mL saline solution, 3 doses of 0.2mL NovoLog Insulin aspart (60 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 80 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 2 doses of 0.2mL saline solution, 4 doses of 0.2mL NovoLog Insulin aspart (80 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 100 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 1 dose of 0.2mL saline solution, 5 doses of 0.2mL NovoLog Insulin aspart (100 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 120 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 6 doses of 0.2mL NovoLog Insulin aspart (120 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;|
| Experimental: Acute Exercise<br>20 minute physical activity period during which participants exercised on a treadmill at an intensity corresponding to 60-65% of maximum heart rate while watching an emotionally neutral video. | Drug: Placebo into the intranasal mucosa<br>* 6 doses of 0.2mL saline solution administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: Saline;Drug: 20 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 5 doses of 0.2mL saline solution, 1 dose of 0.2mL NovoLog Insulin aspart (20 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 40 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 4 doses of 0.2mL saline solution, 2 doses of 0.2mL NovoLog Insulin aspart (40 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 60 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 3 doses of 0.2mL saline solution, 3 doses of 0.2mL NovoLog Insulin aspart (60 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 80 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 2 doses of 0.2mL saline solution, 4 doses of 0.2mL NovoLog Insulin aspart (80 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 100 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 1 dose of 0.2mL saline solution, 5 doses of 0.2mL NovoLog Insulin aspart (100 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;Drug: 120 IU NovoLog Insulin aspart into the intranasal mucosa<br>* 6 doses of 0.2mL NovoLog Insulin aspart (120 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer<br>* Other names: NovoLog Insulin aspart;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Manifestation of Any Symptom at Any Point During the Protocol | The manifestation of any symptom that could be associated with alterations in blood glucose and side effects of intranasal insulin. Fewer symptoms would indicate a better outcome. Burning/tingling of the nose and watering/tearing of the eyes during the nasal spray were the most cited symptoms. | During the 20 minute exercise/control period and the cognitive assessments. | 
| Number of Participants With Manifestation of Any Symptom Following the Protocol | The manifestation of any symptom that could be associated with alterations in blood glucose and side effects of intranasal insulin. Fewer symptoms would indicate a better outcome. The most cited symptom was having a runny nose. | Approximately 1 hour following the dose of intranasal insulin ( 32 minutes following the end of the passive control/exercise condition; immediately following the completion of the post-test cognitive assessments) | 
| Effect Size for Change in Behavioral Index of Inhibitory Control - RT | The effect size of the change from pre-to-posttest in behavioral metrics of performance (RT) on a flanker test of inhibitory control. A more negative effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 
| Effect Size for Change in Behavioral Index of Inhibitory Control - Accuracy | The effect size of the change from pre-to-posttest in behavioral metrics of performance (response accuracy) on a flanker test of inhibitory control. A more positive effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 
| Effect Size of Change in Neuroelectric Index of Attentional Engagement - Inhibition Task | The effect size of the change from pre-to-posttest in neuroelectric measures of attention (P3b amplitude) in response to the flanker test of inhibitory control. The effect size was collapsed across a nine-channel region-of-interest centering around the topographic maxima of the P3 (i.e., the CP3/Z/4, P3/Z/4, PO5/Z/6 electrodes). A larger effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 
| Effect Size of Change in Neuroelectric Index of Attentional Processing Speed - Inhibition Task | The effect size of the change from pre-to-posttest in neuroelectric measures of attention (P3b latency) in response to the flanker test of inhibitory control. The effect size was collapsed across a nine-channel region-of-interest centering around the topographic maxima of the P3 (i.e., the CP3/Z/4, P3/Z/4, PO5/Z/6 electrodes). A smaller effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 
| Effect Size of Change in Behavioral Index of Sustained Attention - RT | The effect size of the change from pre-to-posttest in behavioral metrics of performance (RT) on a Rapid Visual Information Processing test of sustained attention. A more negative effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 
| Effect Size of Change in Behavioral Index of Sustained Attention - Accuracy | The effect size of the change from pre-to-posttest in behavioral metrics of performance (response accuracy) on a Rapid Visual Information Processing test of sustained attention. A more positive effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 
| Effect Size of Change in Neuroelectric Index of Attentional Engagement - RVIP Task | The effect size of the change from pre-to-posttest in neuroelectric measures of attention (P3b amplitude) in response to the target trial of the Rapid Visual Information Processing test of sustained attention. The effect size was collapsed across a nine-channel region-of-interest centering around the topographic maxima of the P3 (i.e., the CP3/Z/4, P3/Z/4, PO5/Z/6 electrodes). A larger effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 
| Effect Size of Change in Neuroelectric Index of Attentional Processing Speed - RVIP Task | The effect size of the change from pre-to-posttest in neuroelectric measures of attention (P3b latency) in response to the target trial of the Rapid Visual Information Processing test of sustained attention. The effect size was collapsed across a nine-channel region-of-interest centering around the topographic maxima of the P3 (i.e., the CP3/Z/4, P3/Z/4, PO5/Z/6 electrodes). A smaller effect size would indicate a better outcome. Effect sizes were computed for each participant as the standardized change relative to the pretest assessment using the within-subject (drm) variance correction for Cohen's d (Lakens, 2013). To ensure the integrity of the effect size estimates, within-subject effect sizes exceeding 3 times the interquartile range were identified as outliers and removed from analysis. Effect sizes are computed per Arm and do not reflect comparisons or combinations across Arms/Groups. | Prior to intranasal insulin administration relative to 30 minutes following | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intranasal Insulin, Cognition, Exercise, Physical Activity