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Different study initiation
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The purpose of this study is to evaluate cognition in smokers and nonsmokers. It involves administration of intranasal insulin (Novolin R), an investigational medication followed by a brief non-invasive cognitive test. All participants will receive both Novolin R and placebo in two separate testing sessions.
This program of research focuses on identifying neurologic biomarkers of smoking behavior in order to develop individualized smoking cessation aids. The intranasal insulin administered is an investigational drug and has been granted IND status by the FDA (IND#129432). During the times of drug effects, the investigators will evaluate a biomarker using computerized tasks. Non-smokers and smokers will participate in two testing sessions where the biomarker will be critically evaluated after administration of intranasal insulin and compared to the cognitive processes elicited by placebo administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Smokers | Experimental | All participants receive both Novolin R (experimental drug) and 14% NaCl (Sodium Chloride) solution (placebo), to be administered in randomly assigned order on two separate testing sessions. During administration of either Novolin R or 14% NaCl, participants will receive 1 spray in each nostril every 3 minutes for a total of 6 sprays. The nasal spray bottle delivers 0.1 ml of liquid per spray. Since the concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver a 60 IU dose. |
|
| Non-Smokers | Experimental | All participants receive both Novolin R (experimental drug) and 14% NaCl solution (placebo), to be administered in randomly assigned order on two separate testing sessions. During administration of either Novolin R or 14% NaCl, participants will receive 1 spray in each nostril every 3 minutes for a total of 6 sprays. The nasal spray bottle delivers 0.1 ml of liquid per spray. Since the concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver a 60 IU dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Novolin R | Drug | Novolin R is a sterile, clear, aqueous, and colorless solution that contains human insulin (rDNA origin) 100 units/mL, glycerol 16 mg/mL, metacresol 3 mg/mL, zinc chloride approximately 7 mcg/mL and water for injection. The pH (potential Hydrogen) is adjusted to 7.4. Hydrochloric acid 2N (concentration) or sodium hydroxide 2N may be added to adjust pH. Novolin R vials are latex-free. The drug substance is being purchased from McKesson. |
| Measure | Description | Time Frame |
|---|---|---|
| Go/No-Go Accuracy | Go/No-Go is used to measure a participants capacity for sustained attention and response control. The test requires a participant to perform an action given certain stimuli (e.g., press a button - Go) and inhibit that action under a different set of stimuli (e.g., not press that same button - No-Go). Average of the 2 runs (run 1 - insulin; run 2 - placebo) were calculated for mean reaction time (+SEM) of smokers and non-smokers on no-go stimuli. The minimum reaction time was 23.08 ms and the maximum reaction time was 97.44 ms. The higher mean value represents slower the reaction time, and the lower mean value represents quicker the reaction time. The higher value means that participants have difficulties with inhibiting a prepotent response. The values do not represent a better or worse outcome. | From time of drug administration to 70 minutes following drug administration, up to 90 minutes |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ajna Hamidovic, PharmD, MS | University of Illinois at Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Illinois Department of Pharmacy Practice | Chicago | Illinois | 60612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9180099 | Background | Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol. 1997 Jun;29(7):1422-31. doi: 10.1016/s0735-1097(97)00079-x. | |
| 24215447 | Background | de la Monte SM. Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art. Expert Opin Drug Deliv. 2013 Dec;10(12):1699-709. doi: 10.1517/17425247.2013.856877. Epub 2013 Nov 12. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Novolin R First, Then Placebo | Participants received active ingredients of intranasal insulin, Novolin R, every 3 minutes for the total of 6 sprays in session 1. Then, participants received placebo intranasal spray every 3 minutes for the total of 6 sprays in session 2. |
| FG001 | Placebo First, Then Novolin R | Participants received placebo intranasal spray every 3 minutes for the total of 6 sprays in session 1. Then, participants received active ingredients of intranasal insulin, Novolin R, every 3 minutes for the total of 6 sprays in session 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (1 Day) |
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| Washout (1 Week) |
| |||||||||||||
| Second Intervention (1 Day) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Novolin R First, Then Placebo | Participants received active ingredients of intranasal insulin, Novolin R, every 3 minutes for the total of 6 sprays in session 1. Then, participants received placebo intranasal spray every 3 minutes for the total of 6 sprays in session 2. |
| BG001 | Placebo First, Then Novolin R |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Go/No-Go Accuracy | Go/No-Go is used to measure a participants capacity for sustained attention and response control. The test requires a participant to perform an action given certain stimuli (e.g., press a button - Go) and inhibit that action under a different set of stimuli (e.g., not press that same button - No-Go). Average of the 2 runs (run 1 - insulin; run 2 - placebo) were calculated for mean reaction time (+SEM) of smokers and non-smokers on no-go stimuli. The minimum reaction time was 23.08 ms and the maximum reaction time was 97.44 ms. The higher mean value represents slower the reaction time, and the lower mean value represents quicker the reaction time. The higher value means that participants have difficulties with inhibiting a prepotent response. The values do not represent a better or worse outcome. | All the participants were non-smokers | Posted | Mean | Standard Deviation | Milliseconds | From time of drug administration to 70 minutes following drug administration, up to 90 minutes |
|
2 sessions, up to 2 days
All-Cause Mortality and Serious Adverse Events were monitored/assessed, but none observed
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Novolin R (First Intervention) | Participants received active ingredients of intranasal insulin, Novolin R, every 3 minutes for the total of 6 sprays in first session. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasal Irritation | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ajna Hamidovic | University of Illinois at Chicago - College of Pharmacy | 312-355-1713 | ahamidov@uic.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Nov 8, 2018 | Nov 9, 2018 | ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 15, 2019 | Nov 19, 2020 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D016540 | Smoking Cessation |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D015438 | Health Behavior |
| D001519 | Behavior |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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The University of Illinois Hospital and Health Sciences System Investigational Drug Service (IDS) randomizes treatment order to study subjects and prepares drug product and placebo. All other roles, including participant, investigator, and non-IDS study personnel are masked from treatment order.
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| 11033313 | Background | Fehm HL, Perras B, Smolnik R, Kern W, Born J. Manipulating neuropeptidergic pathways in humans: a novel approach to neuropharmacology? Eur J Pharmacol. 2000 Sep 29;405(1-3):43-54. doi: 10.1016/s0014-2999(00)00540-9. |
| 19781864 | Background | Franken IH, van Strien JW, Kuijpers I. Evidence for a deficit in the salience attribution to errors in smokers. Drug Alcohol Depend. 2010 Jan 15;106(2-3):181-5. doi: 10.1016/j.drugalcdep.2009.08.014. Epub 2009 Sep 24. |
| 28242873 | Background | Hamidovic A, Khafaja M, Brandon V, Anderson J, Ray G, Allan AM, Burge MR. Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial. Mol Psychiatry. 2017 Oct;22(10):1413-1421. doi: 10.1038/mp.2016.234. Epub 2017 Feb 28. |
| 10078556 | Background | Kern W, Born J, Schreiber H, Fehm HL. Central nervous system effects of intranasally administered insulin during euglycemia in men. Diabetes. 1999 Mar;48(3):557-63. doi: 10.2337/diabetes.48.3.557. |
| 21047524 | Background | Luijten M, van Meel CS, Franken IH. Diminished error processing in smokers during smoking cue exposure. Pharmacol Biochem Behav. 2011 Jan;97(3):514-20. doi: 10.1016/j.pbb.2010.10.012. Epub 2010 Oct 31. |
| 29257872 | Background | Nedelcovych MT, Gadiano AJ, Wu Y, Manning AA, Thomas AG, Khuder SS, Yoo SW, Xu J, McArthur JC, Haughey NJ, Volsky DJ, Rais R, Slusher BS. Pharmacokinetics of Intranasal versus Subcutaneous Insulin in the Mouse. ACS Chem Neurosci. 2018 Apr 18;9(4):809-816. doi: 10.1021/acschemneuro.7b00434. Epub 2018 Jan 4. |
| 21883804 | Background | Ott V, Benedict C, Schultes B, Born J, Hallschmid M. Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism. Diabetes Obes Metab. 2012 Mar;14(3):214-21. doi: 10.1111/j.1463-1326.2011.01490.x. Epub 2011 Nov 16. |
| 24380760 | Background | Rass O, Fridberg DJ, O'Donnell BF. Neural correlates of performance monitoring in daily and intermittent smokers. Clin Neurophysiol. 2014 Jul;125(7):1417-26. doi: 10.1016/j.clinph.2013.12.001. Epub 2013 Dec 11. |
| 17171192 | Background | Reger MA, Craft S. Intranasal insulin administration: a method for dissociating central and peripheral effects of insulin. Drugs Today (Barc). 2006 Nov;42(11):729-39. doi: 10.1358/dot.2006.42.11.1007675. |
| 29508509 | Background | Schmid V, Kullmann S, Gfrorer W, Hund V, Hallschmid M, Lipp HP, Haring HU, Preissl H, Fritsche A, Heni M. Safety of intranasal human insulin: A review. Diabetes Obes Metab. 2018 Jul;20(7):1563-1577. doi: 10.1111/dom.13279. Epub 2018 Apr 6. |
| 22162476 | Background | Shemesh E, Rudich A, Harman-Boehm I, Cukierman-Yaffe T. Effect of intranasal insulin on cognitive function: a systematic review. J Clin Endocrinol Metab. 2012 Feb;97(2):366-76. doi: 10.1210/jc.2011-1802. Epub 2011 Dec 7. |
| 16246040 | Background | Strachan MW. Insulin and cognitive function in humans: experimental data and therapeutic considerations. Biochem Soc Trans. 2005 Nov;33(Pt 5):1037-40. doi: 10.1042/BST20051037. |
| 10823399 | Background | West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl). 2000 Apr;149(3):198-202. doi: 10.1007/s002130000382. |
| NOT COMPLETED |
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| NOT COMPLETED |
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Participants received placebo intranasal spray every 3 minutes for the total of 6 sprays in session 1. Then, participants received active ingredients of intranasal insulin, Novolin R, every 3 minutes for the total of 6 sprays in session 2. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Smokers |
All participants receive both Novolin R (experimental drug) and 14% NaCl (Sodium Chloride) solution (placebo), to be administered in randomly assigned order on two separate testing sessions. During administration of either Novolin R or 14% NaCl, participants will receive 1 spray in each nostril every 3 minutes for a total of 6 sprays. The nasal spray bottle delivers 0.1 ml of liquid per spray. Since the concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver a 60 IU dose. Novolin R: Novolin R is a sterile, clear, aqueous, and colorless solution that contains human insulin (rDNA origin) 100 units/mL, glycerol 16 mg/mL, metacresol 3 mg/mL, zinc chloride approximately 7 mcg/mL and water for injection. The pH (potential Hydrogen) is adjusted to 7.4. Hydrochloric acid 2N (concentration) or sodium hydroxide 2N may be added to adjust pH. Novolin R vials are latex-free. The drug substance is being purchased from McKesson. |
| OG001 | Non-Smokers | All participants receive both Novolin R (experimental drug) and 14% NaCl solution (placebo), to be administered in randomly assigned order on two separate testing sessions. During administration of either Novolin R or 14% NaCl, participants will receive 1 spray in each nostril every 3 minutes for a total of 6 sprays. The nasal spray bottle delivers 0.1 ml of liquid per spray. Since the concentration of insulin in Novolin R is 100 IU/mL, six sprays will deliver a 60 IU dose. Novolin R: Novolin R is a sterile, clear, aqueous, and colorless solution that contains human insulin (rDNA origin) 100 units/mL, glycerol 16 mg/mL, metacresol 3 mg/mL, zinc chloride approximately 7 mcg/mL and water for injection. The pH (potential Hydrogen) is adjusted to 7.4. Hydrochloric acid 2N (concentration) or sodium hydroxide 2N may be added to adjust pH. Novolin R vials are latex-free. The drug substance is being purchased from McKesson. |
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | Placebo (First Intervention) | Participants received placebo intranasal spray every 3 minutes for the total of 6 sprays in first session. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG002 | Placebo (Second Intervention) | Participants received placebo intranasal spray every 3 minutes for the total of 6 sprays in second session. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG003 | Novolin R (Second Intervention) | Participants received active ingredients of intranasal insulin, Novolin R, every 3 minutes for the total of 6 sprays in second session. | 0 | 2 | 0 | 2 | 2 | 2 |
| Sweating | General disorders | Non-systematic Assessment |
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| Sneezing | General disorders | Non-systematic Assessment |
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| Decreased sense of smell, but not total loss | General disorders | Non-systematic Assessment |
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| Partial anosmia (blunted) | General disorders | Non-systematic Assessment |
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| Stinginess | General disorders | Non-systematic Assessment |
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| Hunger | General disorders | Non-systematic Assessment |
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| Dizziness | General disorders | Non-systematic Assessment |
|
| Sinus Pain | General disorders | Non-systematic Assessment |
|
| Pain | General disorders | Non-systematic Assessment |
|
| Burning | General disorders | Non-systematic Assessment |
|
| Taste | General disorders | Non-systematic Assessment |
|
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| D008659 |
| Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |