Clinical trial NCT03169101: Cognition and Smoking Relapse (HCS)
Official title: Understanding the Role of Cognitive Dysfunction in the Treatment of Nicotine Dependence Among HIV-infected Smokers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Smoking Cessation
Keywords: Smoking Cessation
HIV
Cognition
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2017-05-30
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Three hundred (150 HIV+ and 150 HIV-) adult male and female smokers 18 years of age or older who smoke at least 5 cigarettes per day and are interested in quitting smoking will complete the study. HIV-infected smokers have been diagnosed with HIV/AIDS and HIV-uninfected smokers will have no diagnosis of HIV, either via blood test or self-report.

Brief summary: This study tests whether withdrawal-related cognitive deficits increase smoking relapse among HIV-infected (HIV+) vs. HIV-uninfected smokers (HIV-). Adult smokers (N=300; 150 HIV+, 150 HIV-) will complete 2 sessions to assess cognition (24h abstinence vs. smoking-as-usual; order counterbalanced; weeks 0-2). Subjects will then receive smoking cessation counseling and open label transdermal nicotine (weeks 3-12). Outcomes are: 1) cognition; and 2) abstinence rates at the end-of-treatment.

Detailed description: Medical advances in the treatment of HIV/AIDS have improved the life expectancy of HIV-infected individuals. Unfortunately, HIV-infected individuals are three times more likely to use tobacco than those in the general population, but little is known about the mechanisms that underlie these high smoking rates. This will be the first study to test whether the neurocognitive impairments associated with HIV-1 infection may be exacerbated during nicotine withdrawal and increase the probability of smoking relapse among HIV-infected smokers (HIV+), compared to HIV-uninfected smokers (HIV-). To this end, adult treatment-seeking smokers (N=300; 150 HIV+ and 150 HIV-) will complete this 12-week study, which is divided into two phases: a pre-quit laboratory phase (weeks 0-2) and a treatment phase (weeks 3-12). Subjects will complete two laboratory sessions during the pre-quit phase: once following 24 hours of mandatory smoking abstinence and once while smoking-as-usual (order counterbalanced). A comprehensive cognitive task battery assessing memory, attention, and executive function will be administered during each laboratory session. During the treatment phase, all subjects will receive standard smoking cessation treatment, including counseling (weeks 3-8) and open-label transdermal nicotine (TN) patches (weeks 4-12). The primary outcomes are: 1) cognitive performance following 24-hours smoking abstinence (vs. smoking-as-usual) during the pre-quit phase; and 2) 7-day point-prevalence, biochemically-confirmed abstinence rates at the end-of-treatment (EOT) for the treatment phase.

Eligibility criteria: Inclusion Criteria:

* Males and females 18 years of age or older who self-report smoking at least 5 cigarettes (menthol and non-menthol) per day, on average.
* HIV status

  1. HIV-infected smokers: diagnosed with HIV infection and exhibiting viral load of less than or equal to 1000 copies/mL and CD4+ counts of greater than or equal to 200 cells/mm3 within 12 months prior to enrollment.
  2. HIV-uninfected smokers: negative HIV status will be confirmed by an on-site rapid HIV blood test.
* Able to use transdermal nicotine (TN) safely, based on a medical evaluation.
* Residing in the geographic area for at least 4 months.
* Women of childbearing potential (based on medical history) must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are in the study and using transdermal nicotine.
* Able to communicate fluently in English.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent/HIPAA form.

Exclusion Criteria:

Smoking Behavior

1. Current enrollment or plans to enroll in another smoking cessation program in the next 4 months.
2. Regular (daily) use of electronic cigarettes, chewing tobacco, snuff, snus, cigars, cigarillos, or pipes.
3. Current use or plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) or smoking cessation treatments in the next 4 months.

Alcohol/Drug Exclusion Criteria

1. Current untreated and unstable diagnosis of substance dependence (eligible if past use and if receiving treatment and stable for at least 30 days). Current untreated and unstable diagnosis of substance abuse requires Study Physician approval.
2. A positive urine drug screen for cocaine, amphetamines, methamphetamines, Phencyclidine (PCP), barbiturates, ecstasy (MDMA) at Intake (see Measures and Table 1 for details). At Lab 1 and Lab 2, positive urine drug screens will be reviewed on a case-by-case basis. The PI will determine if the participant will be excluded or allowed to reschedule the visit, at which time they must provide a negative drug screen to continue with the study.

Medication Exclusion Criteria

Current use or recent discontinuation (within last 14 days) of the following medications:

1. Other smoking cessation medications (e.g. Zyban, Wellbutrin, Wellbutrin sustained release (SR), Chantix)

   a. Note: Once participants are found eligible for the study, they are instructed to only use the NRT provided to them by the study staff. If a subject reports using a non-study smoking cessation medication (including other forms of NRT), the study physician and PI will evaluate the situation and determine if it is safe for the subject to continue participation.
2. Anti-psychotic medications (if used to treat psychotic symptoms. Other uses may be eligible pending physician approval).
3. Daily use of opiate-containing medications for chronic pain (Duragesic/fentanyl patches, Percocet, Oxycontin). Smokers who report taking opiate-containing medications on an "as-needed" basis will be instructed to refrain from use until their study participation is over and that they will be tested to ensure they have complied with this requirement.
4. Asthma medications/corticosteroids (requires physician approval)
5. Anti-depressants (require physician approval)

Medical Exclusion Criteria

1. Females who self-report current pregnancy, planning a pregnancy during the study, or currently breastfeeding/lactating.
2. Current diagnosis of unstable and untreated major depression, as determined by self-report \& Mini International Neuropsychiatric Interview (MINI) (eligible if stable for at least 30 days).
3. Current or past diagnosis of bipolar disorder or psychotic disorder, as determined by self-report or MINI.
4. History of heart disease, stroke or MI, unstable angina, or tachycardia (if stable, requires Study Physician approval).
5. Uncontrolled hypertension (systolic blood pressure (SBP) greater than 160 or diastolic blood pressure (DBP) greater than 100) present at Intake.

   a. Note: If a participant presents with blood pressure greater than 160/100 at sessions occurring on Week 3 (Pre-Quit) or at any other point during the treatment period, they will not be provided with/able to continue on TN unless the study physician grants approval.
6. Previous allergic reaction to TN.
7. History of diabetes (requires Study Physician approval)
8. History of seizures (requires Study Physician approval)
9. History of stomach ulcers (requires Study Physician approval)

Suicide History Exclusion Criteria

1. Suicide risk as indicated by at least one of the following on the Columbia Suicide Severity Rating Scale (the PI \&/or study psychologist will be consulted to assess safety and determine eligibility in cases close to the eligibility cutoffs):

1. Current suicidal ideation (within 30 days of enrollment)
2. Two or more lifetime suicide attempts
3. Any suicide attempt within 2 years of enrollment

General Exclusion Criteria

1. Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.
2. Color blindness.
3. Any impairment (physical and/or neurological) including visual or other impairment preventing cognitive task performance.
4. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.

Primary outcomes:
measure: Cognitive Function
timeFrame: Lab session 1 (week 1), lab session 2 (week 2), End of treatment (week 12)
Secondary outcomes:
measure: 7-day Point Prevalence Abstinence
timeFrame: End of Treatment (week 12)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Rebecca L Ashare, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: