Neuro Biomarkers of Smoking Behavior

NCT ID: NCT03811951

Last Updated: 2021-03-02

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-12

Study Completion Date

2019-09-27

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.

Conditions

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Smoking Cessation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

DOUBLE

Participants Investigators
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.

Study Groups

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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.

Group Type EXPERIMENTAL

Novolin R

Intervention Type 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.

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.

Group Type EXPERIMENTAL

Novolin R

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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McKesson Corporation, Novo Nordisk

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
Minimum Eligible Age

21 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Illinois at Chicago

OTHER

Sponsor Role lead

Responsible Party

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Ajna Hamidovic, PharmD, MS

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ajna Hamidovic, PharmD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

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University of Illinois Department of Pharmacy Practice

Chicago, Illinois, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 9180099 (View on PubMed)

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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PMID: 24215447 (View on PubMed)

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Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
PMID: 28242873 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10078556 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
PMID: 29257872 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21883804 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24380760 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17171192 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29508509 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22162476 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16246040 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10823399 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-1288

Identifier Type: -

Identifier Source: org_study_id

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