Clinical trial NCT03811951: Neuro Biomarkers of Smoking Behavior
Official title: Neurologic Biomarkers of Smoking Behavior
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Smoking Cessation
Keywords: Tobacco
Cigarettes
Nicotine
Insulin
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
First posted: 2019-01-22
Enrollment: 4
Sex: ALL
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Go/No-Go Accuracy
timeFrame: From time of drug administration to 70 minutes following drug administration, up to 90 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Department of Pharmacy Practice
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Ajna Hamidovic, PharmD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.