Safety and Efficacy of Combining Intranasal Insulin & Acute Exercise

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

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

Study Overview

• Status: Completed
• Conditions: Exercise; Insulin
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Department of Kinesiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants must be over the age of 18..
2. Participants must have normal or corrected-to-normal vision in order to complete the cognitive task.

Exclusion Criteria:

1. Lack of consent.
2. Presence of any major neurological health issues, brain trauma, or concussion with loss of consciousness assessed through a health history and demographics questionnaire.
3. Type I or Type II Diabetes
4. Self-reported pregnancy
5. Currently has any type of inflammation or blockage of the nasal passageways (i.e. allergies or a cold affecting the sinuses).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Passive Control; 20 minute sedentary control period during which participants watched an emotionally neutral video.	Drug: Placebo into the intranasal mucosa; 6 doses of 0.2mL saline solution administered into the intranasal mucosa using the MAD Nasal Atomizer; Other Names: Saline; Drug: 20 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 40 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 60 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 80 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 100 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 120 IU NovoLog Insulin aspart into the intranasal mucosa; 6 doses of 0.2mL NovoLog Insulin aspart (120 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer; Other Names: NovoLog Insulin aspart
Experimental: Acute Exercise; 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; 6 doses of 0.2mL saline solution administered into the intranasal mucosa using the MAD Nasal Atomizer; Other Names: Saline; Drug: 20 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 40 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 60 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 80 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 100 IU NovoLog Insulin aspart into the intranasal mucosa; 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; Other Names: NovoLog Insulin aspart; Drug: 120 IU NovoLog Insulin aspart into the intranasal mucosa; 6 doses of 0.2mL NovoLog Insulin aspart (120 IU) administered into the intranasal mucosa using the MAD Nasal Atomizer; Other Names: NovoLog Insulin aspart

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Michigan State University
• Investigators: Principal Investigator: Matthew B Pontifex, Ph.D., Michigan State University

Publications and helpful links

General Publications

• Gwizdala KL, Ferguson DP, Kovan J, Novak V, Pontifex MB. Placebo controlled phase II clinical trial: Safety and efficacy of combining intranasal insulin & acute exercise. Metab Brain Dis. 2021 Aug;36(6):1289-1303. doi: 10.1007/s11011-021-00727-2. Epub 2021 Apr 15.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): February 20, 2020

Study Registration Dates

• First Submitted: February 28, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Physical Activity; Exercise; Cognition; Intranasal Insulin
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: STUDY00000804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data sharing will be by request and approval of the Michigan State University Human Research Protections Program with the provision of a data-safety and sharing agreement. No individually identifiable information will be shared.
• IPD Sharing Time Frame: Data will be available following primary publication of the results.
• IPD Sharing Access Criteria: By request
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No