Neuro Biomarkers of Smoking Behavior

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Neurologic Biomarkers of Smoking Behavior

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Novolin R


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 21-40 years Smokers only: Begin smoking within 5 minutes of waking (verified by carbon monoxide concentrations greater than 10 ppm). Non-smokers only: No self-reported cigarette use in the past 1-year period. Non-smokers only: Carbon monoxide concentration < 6 ppm. Normal vitals (blood pressure < 120/80 mmHg; heart rate between 60 and 100 bpm, body temperature <37 °C) Point-of-care (POC) blood glucose between 80 and 140 mg/dL Body mass index between 18.5 and 30 kg/m2 Exclusion Criteria: Use of non-cigarette tobacco products, e-cigarettes, or smoking cessation treatment Positive urine drug screen test Current pregnancy (urine test-verified) or lactation, or a plan to become pregnant Breath Alcohol Concentration >0.00% Shipley IQ (Intelligence Quotient) test <80 Hyposmic or anosmic individuals (identifying less than 10 of 12 smells correctly) Abnormal physical exam of the nares Lifetime DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-5) Axis 1 disorder (except anxiety and depression) Current DSM-5 Axis depression or anxiety disorder Prescription medications Over-the-counter psychotropic medications Use of any medications administered intranasally Allergies to any ingredients in intranasal insulin or placebo Braided hair that would cause noise in EEG recording

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 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: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Smokers<br>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. | Drug: Novolin R<br>* 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.<br>* Other names: McKesson Corporation, Novo Nordisk;|
| Experimental: Non-Smokers<br>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. | Drug: Novolin R<br>* 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.<br>* Other names: McKesson Corporation, Novo Nordisk;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tobacco, Cigarettes, Nicotine, Insulin