Neuro Biomarkers of Smoking Behavior

Smoking Cessation Clinical Trial

Official title:

Neurologic Biomarkers of Smoking Behavior

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03811951
• Other study ID #: 2017-1288
• Status: Terminated
• Phase: Phase 2
• Start date: September 12, 2018
• Est. completion date: September 27, 2019

Study information

• Verified date: March 2021
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 27, 2019
• Est. primary completion date: September 27, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Smoking Cessation

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	University of Illinois Department of Pharmacy Practice	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

References & Publications (15)

Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol. 1997 Jun;29(7):1422-31. Review. — View 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. Review. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. Review. — View Citation

Schmid V, Kullmann S, Gfrörer W, Hund V, Hallschmid M, Lipp HP, Häring 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. — View 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. Review. — View Citation

Strachan MW. Insulin and cognitive function in humans: experimental data and therapeutic considerations. Biochem Soc Trans. 2005 Nov;33(Pt 5):1037-40. Review. — View 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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From time of drug administration to 70 minutes following drug administration, up to 90 minutes