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Nicotinic Hepatic Metabolism on Neuroreceptor Substrates of Nicotine Addiction

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ClinicalTrials.gov Identifier: NCT03442413
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Jacob Dubroff, University of Pennsylvania

Brief Summary:

Physically healthy adult smokers may be eligible for this study. Volunteers may participate in this study if they are 18 - 65 years old.

Subjects will participate in two separate 10-hour PET/CT Scan Sessions (each with 2 hours of actual PET/CT scanning): one following an overnight abstinence and one following two overnights of abstinence. To achieve and confirm two overnights of abstinence, participants will present to the inpatient CHPS the day prior to the scheduled scan and stay overnight.

The 2-[18F]-FA PET/CT brain scans will consist of an injection followed by an 8-hour infusion of 2-[18F]-FA. The scan session will begin at approximately 6 hours after the bolus injection. The PET/CT scan will be approximately 120 minutes long with a bolus injection of IV nicotine that will occur during scanning at approximately 30 minutes into the procedure. The pre and post nicotine images will be analyzed to evaluate for differences in receptor uptake after the nicotine "challenge".

Subjects will have a structural Brain MRI performed within 1 year of study enrollment. Subjects who have not had a Brain MRI that is deemed acceptable for use for this study will undergo a research Brain MRI.


Condition or disease Intervention/treatment Phase
Smoking, Tobacco Drug: 2-[18F]-FA PET/CT Drug: I.V. Nicotine Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: The Influence of Nicotinic Hepatic Metabolism on Neuroreceptor Substrates of Nicotine Addiction
Actual Study Start Date : May 15, 2018
Estimated Primary Completion Date : March 13, 2020
Estimated Study Completion Date : March 13, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 2-[18F]-FA PET/CT
Subjects will participate in two separate 10-hour PET/CT Scan Sessions (each with 2 hours of actual PET/CT scanning): one following an overnight abstinence and one following two overnights of abstinence. To achieve and confirm two overnights of abstinence, participants will present to the inpatient CHPS the day prior to the scheduled scan and stay overnight
Drug: 2-[18F]-FA PET/CT
2-[18F]FA is a highly specific radiotracer which has been used successfully to image nicotinic acetylcholine receptors in the human brain to characterize the effects of nicotine exposure (via smoking) on these receptors.

Drug: I.V. Nicotine
Subjects in our study will receive intravenous nicotine at the adaptation session and each of the PET scans, close to the amount of nicotine absorbed from smoking 1/10 cigarette.




Primary Outcome Measures :
  1. Duration of abstinence affects brain nAChR availability in smokers [ Time Frame: 2 years ]
    To determine how duration of abstinence affects brain nAChR availability in smokers who metabolize nicotine at slow and normal rates (measured by the nicotine-metabolite ratio (NMR)).

  2. How nicotine administration affects nAChR availability during early abstinence in smokers [ Time Frame: 2 years ]
    To compare how nicotine administration affects nAChR availability during early abstinence in smokers who metabolize nicotine at slow and normal rates (measured by the NMR).


Secondary Outcome Measures :
  1. Standard measures of cigarette craving and withdrawal to nAChR availability in smokers [ Time Frame: 2 years ]
    To correlate standard measures of cigarette craving and withdrawal to nAChR availability in smokers who metabolize nicotine at slow and normal rates (measured by the NMR) who are abstinent, before and after administration of IV nicotine



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Participants will be 18-65 years of age
  2. Self-reported cigarette smoking history of at least 10 cigarettes/day for at least 6 months prior to enrollment
  3. Carbon monoxide reading > 10 ppm at the initial screening session
  4. Participants agree to be compliant with all study procedures including smoking abstinence and willingness to complete over-night stays at the Hospital of the University of Pennsylvania
  5. Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria:

  1. Women who are pregnant at the time of screening will not be eligible for this study. A urine pregnancy test will be performed in women of childbearing potential at screening.
  2. Self-reported regular (daily) use of chewing tobacco, snuff or snus
  3. Current enrollment in a smoking cessation or research program involving the use of nicotine substitutes
  4. History within one year or currently receiving treatment for substance abuse other than nicotine (e,g,, alcohol, opioids, cocaine, marijuana, or stimulants)
  5. Current use of cocaine, methamphetamines or other psychoactive substances per self-report and/or positive urine drug screen at the initial screening session
  6. Self-reported current alcohol consumption that exceeds greater than 25 drinks per week in men and 18 drinks per week in women
  7. BrAC reading greater than or equal to 0.01% at the initial screening session
  8. History of kidney and/or liver disease per medical record review or self-reported
  9. Uncontrolled hypertension (defined as Systolic BP > 160 and/or Diastolic BP > 100 at the screening intake session)
  10. History of Posttraumatic Stress Disorder (PTSD), bipolar disorder, schizophrenia or other psychotic disorder or Attention-Deficit/Hyperactivity Disorder (ADHD) as assessed by medical record review and/or self-report. History of unipolar depression or anxiety disorder may be accepted; current depression or anxiety may be accepted if the severity does not require psychoactive medication as assessed by medical record review and/or self-report.
  11. History of head trauma, that in the opinion of an investigator may interfere with the uptake of [18F]2-FA, as assessed by medical record review and/or self-report
  12. Current use or recent discontinuation (within the last 14 days) of any of the following:

    1. Smoking cessation medication (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix).
    2. Anti-psychotic medications.
    3. Certain medications used to treat depression, including SSRIs, Wellbutrin, MAOIs, and tricyclic antidepressants.
    4. Prescription stimulants (e.g. Provigil, Ritalin, Adderall).
  13. Current use of any of the following:

    1. Nicotine replacement therapy (NRT).
    2. Tagamet (cimetidine).
    3. Heart medications such as digoxin, quinidine, nitroglycerin. Use of these medications may result in ineligibility and will therefore be evaluated on a case-by-case basis by the Study Physician.
    4. Anti-coagulants (e.g. Coumadin, Warfarin).
  14. Daily use of any of the following:

    1. Opiate-containing medications for chronic pain; If a participant reports taking an opiate-containing medication every day for the 14 days prior to the telephone screen and/or the Intake Session, the participant will be ineligible.
    2. Rescue Inhalers (e.g. Albuterol, Proventil, Ventolin, or Maxair).
  15. Any contraindication to brain MRI
  16. Any current medical condition, psychiatric disorder, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03442413


Contacts
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Contact: Erin Schubert 215-573-6569 erinschu@pennmedicine.upenn.edu

Locations
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United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Erin Schubert    215-573-6569    Erin.Schubert@uphs.upenn.edu   
Sponsors and Collaborators
University of Pennsylvania

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Responsible Party: Jacob Dubroff, Principal Investigator, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03442413     History of Changes
Other Study ID Numbers: 828090
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action