Brain Nicotine Receptor Density in Veteran Smokers

NCT ID: NCT01721473

Last Updated: 2019-10-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

184 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-01-01

Study Completion Date

2016-06-30

Brief Summary

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Cigarette smoking is more prevalent among Veterans (27%) than the general U.S. population (21%). Smoking is common among people who use marijuana or caffeine heavily, and the use of menthol cigarettes is becoming increasingly common, affecting approximately 9% of the Veteran population. Recent research by the group and others indicates that heavy marijuana or caffeine use, or the use of predominantly menthol cigarettes, can alter brain nicotinic acetylcholine receptor (nAChR) densities. For the proposed study, brain imaging with PET scanning will be used to determine nicotine receptor densities in Veteran cigarette smokers with and without heavy marijuana or caffeine use, and in menthol and non-menthol Veteran smokers. Results of the proposed research may have implications for improving treatments for Veterans who smoke cigarettes and who have specific drug use co-morbidities or who use menthol cigarettes.

Detailed Description

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Despite improvements in tobacco control, the prevalence of Tobacco Dependence (TD) remains high at 27% among Veterans and 21% among the general U.S. population (\~46 million U.S. adults). Both co-morbid substance use and menthol cigarette preference are important issues contributing to greater severity of TD. Among smokers, a lifetime history of substance use/dependence is common and approximately 33% of all smokers use primarily menthol cigarettes, meaning that roughly 9% of Veterans smoke menthol. In addition to menthol cigarette usage being prevalent among Veterans, this problem is likely to worsen over time, because recent military deployments increase the chances of smoking initiation and marketing of menthol cigarettes is aimed at roughly the age group that comprises the active military.

For substance use/dependence, marijuana (MJ) users are five times more likely than non-MJ users to smoke tobacco cigarettes, and regular caffeine users are twice as likely as non-caffeine users to smoke cigarettes. Cigarette smoking contributes greatly to morbidity and mortality among patients with drug (and alcohol) dependencies, making it vital to understand better the complex relationship between drug/alcohol dependence and brain nicotine receptor densities in cigarette smokers.

Based on prior literature and pilot data collected during the previous Merit Review period, the primary hypotheses for the proposed research are that: 1) Participants who are heavy MJ users will have higher 4 2\* nAChR densities in the thalami (and other brain regions) than participants who are not heavy MJ users, 2) Participants who are daily heavy caffeine users will have lower 4 2\* nAChR densities in the thalami (and other regions) than participants who are not heavy daily caffeine users, 3) Densities of 4 2\* nAChRs in the thalami (and other brain regions of interest) will be higher in menthol than non-menthol cigarette smokers, and 4) lesser severity of 4 2\* nAChR up-regulation at baseline (along with clinical factors such as lesser severity of nicotine dependence) will be associated with better treatment outcomes in a standard smoking cessation program, including an improved likelihood of quitting and/or decreasing smoking.

To test these hypotheses, cigarette smokers will be recruited through flyers posted at the VA Greater Los Angeles Healthcare System in areas where smokers are likely to be present. Participants will undergo the following sequence of procedures: (1) telephone/in-person screening, (2) a bolus-plus-continuous-infusion 2-FA positron emission tomography (PET) scanning session, (3) a structural magnetic resonance imaging scan within one week of the initial PET session, and (4) referral to a standard 12-week smoking cessation program. Rating scales for the determination of smoking-related symptoms will be collected before and during the PET scanning procedure. Smoking status and measures of nicotine exposure and metabolism will be collected during the study using participant reports, exhaled carbon monoxide (CO) levels, urine cotinine levels, and plasma nicotine, cotinine, and 3'-hydroxycotinine levels.

Conditions

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Positron Emission Tomography

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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cigarette smokers with heavy marijuana use

With heavy marijuana use

positron emission tomography scan

Intervention Type OTHER

2-FA positron emission tomography scan

cigarette smokers with heavy caffeine use

with heavy caffeine use

positron emission tomography scan

Intervention Type OTHER

2-FA positron emission tomography scan

cigarette smokers w/o heavy caffeine and marijuana use

cigarette smokers without the heavy use of marijuana or caffeine

positron emission tomography scan

Intervention Type OTHER

2-FA positron emission tomography scan

non-smokers

not a regular cigarette user

positron emission tomography scan

Intervention Type OTHER

2-FA positron emission tomography scan

cigarette smokers with non-menthol cigarette preference

non-menthol cigarette preference

positron emission tomography scan

Intervention Type OTHER

2-FA positron emission tomography scan

cigarette smokers with menthol cigarette preference

menthol cigarette preference

positron emission tomography scan

Intervention Type OTHER

2-FA positron emission tomography scan

Interventions

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positron emission tomography scan

2-FA positron emission tomography scan

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Must be a Veteran cigarette smoker, living within commuting distance of the VA San Diego Healthcare System
* Healthy adult Veterans (18 to 65 years old) who are tobacco dependent cigarette smokers (10 to 40 cigarettes per day) meeting criteria for Nicotine Dependence as defined by DSM-IV criteria109 and who want to quit smoking.
* Heavy marijuana or caffeine use (defined as using the equivalent of \> 2 marijuana cigarettes per week or the use of at least 3 coffee cup equivalents per day) for at least the past 6 months or no heavy drug/alcohol use.
* Ability to read, write, and give voluntary informed consent.
* An exhaled CO \> 8 ppm during the study screening visit to verify smoking status.

Exclusion Criteria

* Any Axis I diagnosis (including mood, anxiety, and psychotic disorders) other than Nicotine, Marijuana, or Caffeine Dependence within the past 1 year.
* A current diagnosis (within the past month) of other substance abuse/dependence diagnoses (such as cocaine, amphetamine, or opiates). (Length of abstinence will be verified through participant interview and a chart review at the initial study visit, which typically includes information about substance abuse treatment history and objective verification with breathalyzer and/or urine toxicology screens). Occasional drug/alcohol use not meeting criteria for abuse/dependence will not be exclusionary.
* Any current medication or any history of a medical condition that might affect the central nervous system at the time of scanning (e.g., current treatment with a psychotropic medication, or history of severe head trauma with loss of consciousness, epilepsy, or other neurological diseases).
* The combination of both heavy marijuana and caffeine use.
* Unstable cardiovascular disease, severe liver disease, or renal insufficiency, which might make tolerating study procedures difficult. Routine history and physical examination will be performed at the initial screening visit to insure that participants meet study criteria (Section D4).
* Pregnancy (urine pregnancy tests will be obtained on all women of childbearing potential) due to the theoretical risk of radiation exposure to the fetus.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arthur L Brody, MD

Role: PRINCIPAL_INVESTIGATOR

VA San Diego Healthcare System, San Diego, CA

Locations

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VA San Diego Healthcare System, San Diego, CA

San Diego, California, United States

Site Status

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States

Site Status

Countries

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United States

References

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Potenza MN, Brody AL. Commentary on Boileau et al. (2013): Distinguishing D2/D3 dopaminergic contributions to addictions. Addiction. 2013 May;108(5):964-5. doi: 10.1111/add.12119. No abstract available.

Reference Type BACKGROUND
PMID: 23587083 (View on PubMed)

Jasinska AJ, Zorick T, Brody AL, Stein EA. Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans. Neuropharmacology. 2014 Sep;84:111-22. doi: 10.1016/j.neuropharm.2013.02.015. Epub 2013 Mar 6.

Reference Type BACKGROUND
PMID: 23474015 (View on PubMed)

Brody AL, Mukhin AG, Stephanie Shulenberger, Mamoun MS, Kozman M, Phuong J, Neary M, Luu T, Mandelkern MA. Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density. Neuropsychopharmacology. 2013 Jul;38(8):1548-56. doi: 10.1038/npp.2013.53. Epub 2013 Feb 21.

Reference Type BACKGROUND
PMID: 23429692 (View on PubMed)

Jarcho JM, Feier NA, Bert A, Labus JA, Lee M, Stains J, Ebrat B, Groman SM, Tillisch K, Brody AL, London ED, Mandelkern MA, Mayer EA. Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain. Pain. 2013 Jul;154(7):987-96. doi: 10.1016/j.pain.2013.02.026. Epub 2013 Mar 5.

Reference Type BACKGROUND
PMID: 23582152 (View on PubMed)

Storage S, Mandelkern MA, Phuong J, Kozman M, Neary MK, Brody AL. A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability. Psychiatry Res. 2013 Dec 30;214(3):415-21. doi: 10.1016/j.pscychresns.2013.07.010. Epub 2013 Oct 19.

Reference Type BACKGROUND
PMID: 24148908 (View on PubMed)

Xu J, Fregni F, Brody AL, Rahman AS. Transcranial direct current stimulation reduces negative affect but not cigarette craving in overnight abstinent smokers. Front Psychiatry. 2013 Sep 20;4:112. doi: 10.3389/fpsyt.2013.00112. eCollection 2013.

Reference Type BACKGROUND
PMID: 24065930 (View on PubMed)

Le Foll B, Guranda M, Wilson AA, Houle S, Rusjan PM, Wing VC, Zawertailo L, Busto U, Selby P, Brody AL, George TP, Boileau I. Elevation of dopamine induced by cigarette smoking: novel insights from a [11C]-+-PHNO PET study in humans. Neuropsychopharmacology. 2014 Jan;39(2):415-24. doi: 10.1038/npp.2013.209. Epub 2013 Aug 19.

Reference Type BACKGROUND
PMID: 23954846 (View on PubMed)

Zanchi D, Brody AL, Montandon ML, Kopel R, Emmert K, Preti MG, Van De Ville D, Haller S. Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate. Addict Biol. 2015 Nov;20(6):1033-41. doi: 10.1111/adb.12292. Epub 2015 Aug 25.

Reference Type BACKGROUND
PMID: 26303184 (View on PubMed)

Brody AL, Zorick T, Hubert R, Hellemann GS, Balali S, Kawasaki SS, Garcia LY, Enoki R, Abraham P, Young P, McCreary C. Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers With Schizophrenia: A Randomized Controlled Trial. Nicotine Tob Res. 2017 Jan;19(1):68-76. doi: 10.1093/ntr/ntw190. Epub 2016 Aug 3.

Reference Type BACKGROUND
PMID: 27613888 (View on PubMed)

Xie J, Douglas PK, Wu YN, Brody AL, Anderson AE. Decoding the encoding of functional brain networks: An fMRI classification comparison of non-negative matrix factorization (NMF), independent component analysis (ICA), and sparse coding algorithms. J Neurosci Methods. 2017 Apr 15;282:81-94. doi: 10.1016/j.jneumeth.2017.03.008. Epub 2017 Mar 18.

Reference Type BACKGROUND
PMID: 28322859 (View on PubMed)

Brody AL, Mukhin AG, La Charite J, Ta K, Farahi J, Sugar CA, Mamoun MS, Vellios E, Archie M, Kozman M, Phuong J, Arlorio F, Mandelkern MA. Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers. Int J Neuropsychopharmacol. 2013 Jun;16(5):957-66. doi: 10.1017/S1461145712001022. Epub 2012 Nov 21.

Reference Type RESULT
PMID: 23171716 (View on PubMed)

Brody AL, Mukhin AG, Mamoun MS, Luu T, Neary M, Liang L, Shieh J, Sugar CA, Rose JE, Mandelkern MA. Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial. JAMA Psychiatry. 2014 Jul 1;71(7):797-805. doi: 10.1001/jamapsychiatry.2014.138.

Reference Type RESULT
PMID: 24850280 (View on PubMed)

Zorick T, Mandelkern MA, Brody AL. A naturalistic study of the association between antidepressant treatment and outcome of smoking cessation treatment. J Clin Psychiatry. 2014 Dec;75(12):e1433-8. doi: 10.4088/JCP.14m09012.

Reference Type RESULT
PMID: 25551240 (View on PubMed)

Brody AL, McClernon FJ. Prediction of smoking cessation with treatment: the emerging contribution of brain imaging research. Neuropsychopharmacology. 2015 May;40(6):1309-10. doi: 10.1038/npp.2015.31. No abstract available.

Reference Type RESULT
PMID: 25868069 (View on PubMed)

Dubroff JG, Doot RK, Falcone M, Schnoll RA, Ray R, Tyndale RF, Brody AL, Hou C, Schmitz A, Lerman C. Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism. J Nucl Med. 2015 Nov;56(11):1724-9. doi: 10.2967/jnumed.115.155002. Epub 2015 Aug 13.

Reference Type RESULT
PMID: 26272810 (View on PubMed)

Brody AL, Hubert R, Mamoun MS, Enoki R, Garcia LY, Abraham P, Young P, Mandelkern MA. Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use. Psychopharmacology (Berl). 2016 Sep;233(17):3249-57. doi: 10.1007/s00213-016-4367-x. Epub 2016 Jul 1.

Reference Type RESULT
PMID: 27370018 (View on PubMed)

Brody AL, Hubert R, Enoki R, Garcia LY, Mamoun MS, Okita K, London ED, Nurmi EL, Seaman LC, Mandelkern MA. Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study. Neuropsychopharmacology. 2017 Jul;42(8):1630-1639. doi: 10.1038/npp.2017.48. Epub 2017 Mar 6.

Reference Type RESULT
PMID: 28262740 (View on PubMed)

Other Identifiers

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NURA-02-11S

Identifier Type: -

Identifier Source: org_study_id

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