Cigarette SmokingPhase 1NSSNCT03670212
Investigation of Nicotine Seeking Behavior in Current Smokers
A Phase 1 study testing Yohimbine Hydrochloride, Hydrocortisone and Lactose Monohydrate Powder in people with Cigarette Smoking, run by Wayne State University at 1 site in United States.
Trial summary
In this study, 21 non-treatment-seeking cigarette smokers were recruited to investigate the effects of acute stress on brain function and nicotine seeking/self-administration behavior. Read more about this study
- Who is it for?
- Ages 21 to 35 years
- Conditions the study is for
- Cigarette Smoking
- What is being tested?
- Yohimbine Hydrochloride, Hydrocortisone and Lactose Monohydrate Powder
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jan 2016to 4 Oct 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 1) Aged between 21-35 years old, 2) current smokers (expired breath carbon monoxide > 4ppm, self-reported 10+ cigarettes/day, Fagerstrom test for nicotine dependence score > 3, 3) normal seated and resting vital signs (systolic blood pressure 80-160mmHg, diastolic blood pressure 50-90mmHg, and heart rate 50-90 bpm), and 4) normal or corrected-normal vision.
Who cannot join
- 1) Abnormal electrocardiogram (reviewed by licensed cardiologist), 2) magnetic resonance imaging contraindications (e.g. metal implants), 3) medical/neurological contraindications (e.g., diabetes or head trauma), 4) pregnancy (urine test; females only), 5) positive urine test result for opioids, cocaine metabolites, benzodiazepines, barbiturates, or amphetamines, 6) psychiatric contraindications (subject met criteria for current Axis 1 disorder [other than nicotine dependence] as indicated by computerized MINI-6 screen), and 7) self-reported marijuana and/or alcohol use on 15+ days in the past month.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neuropharmacological Investigation of Frontostriatal Network Function and Nicotine Seeking Behavior in Current Smokers
In this study, 21 non-treatment-seeking cigarette smokers were recruited to investigate the effects of acute stress on brain function and nicotine seeking/self-administration behavior.
Read the detailed description
Non-treatment-seeking cigarette smoking individuals were recruited from the Detroit, MI area. Individuals were screened for cardiovascular, neurological, and psychiatric contraindications. 21 healthy smokers completed two oral pre-treatment experimental sessions (on separate non-consecutive days) in randomized order under double-blind conditions: placebo (lactose) and stress (54mg yohimbine and 10mg hydrocortisone). Yohimbine + hydrocortisone elicit a neurochemical and physiological response that mimics a 'natural' stressor. Placebo and stress sessions were identical and started at 11am. Upon arrival, subject sobriety was confirmed with expired breath alcohol measurement (<.02%). At 11:30am, each subject smoked 6 cigarette puffs (preferred brand; provided by study) over 5 minutes to control for recent nicotine exposure. Throughout each experimental session, subjects periodically completed self-reported measures of cigarette craving, nicotine withdrawal symptoms, affect, and anxiety, and vital signs were measured. Subjects self-administered (swallowed) oral doses of yohimbine (or placebo) at 11:45am and hydrocortisone (or placebo) at 12:15pm. At 1pm, subjects completed a 60-min neuroimaging scan which included: 1) T1-weighted structural scan, 2) proton functional magnetic resonance spectroscopy (fMRS) acquisition from the left prefrontal cortex during a letter 2-back working memory paradigm, and 3) functional magnetic resonance imaging (fMRI) acquisition during an N-back paradigm yoked with cigarette cues. At 2:30pm, subjects completed an 11-trial choice progressive ratio task in which they could earn cigarette puffs (preferred brand; provided by study) or money. At 3pm, subjects self-administered earned cigarette puffs (video monitored). Subjects remained on site until 4pm discharge.
- Conditions
- Cigarette Smoking
- Being tested
- Yohimbine Hydrochloride, Hydrocortisone, Lactose Monohydrate Powder
- Keywords
- cigarette smoking, acute stress, executive function, craving, nicotine seeking, relapse, excitatory neural activity, glutamate, negative affect
- Medical subject headings
- Cigarette Smoking, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Yohimbine HydrochlorideDrug
Also called YOH
54mg of yohimbine powder was encapsulated in a generic opaque capsule and swallowed with water.
HydrocortisoneDrug
Also called HYD
10mg hydrocortisone was encapsulated in a generic opaque capsule and swallowed with water.
Lactose Monohydrate PowderDrug
Also called Placebo
Lactose powder was encapsulated in generic opaque capsules identical to those used during the acute stress session. Lactose doses weighed the same as the acute stress session doses (54mg and 10mg, respectively).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | The placebo compound, Lactose Monohydrate Powder, was encapsulated in generic opaque capsules identical to the capsules used in the acute stress session. During the placebo session, two capsules were self-administered (swallowed) by each subject. At 11:45am, subjects self-administered a capsule containing 54mg of lactose. At 12:15pm, subjects self-administered a capsule containing 10mg of lactose. Receives: Drug: Lactose Monohydrate Powder |
| Acute Stress | Experimental | During the acute stress experimental session, subjects self-administered two generic opaque capsules. At 11:45am, subjects self-administered a capsule containing 54mg of Yohimbine Hydrochloride powder. At 12:15pm, subjects self-administered a capsule containing 10mg of Hydrocortisone. Receives: Drug: Yohimbine Hydrochloride; Drug: Hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cigarette puff vs. money choice task
Participants could earn (via computer mouse 'clicks') money or cigarette puffs (preferred brand; provided by the study) across 11 independent choice trials. At the start of each trial, subjects selected either money or cigarette puffs on a computer screen. After each selection, subjects could earn one unit of that selection by satisfying the computer 'mouse' click requirement. The click requirement increased with each successive unit earned separately for cigarette puffs and money following a progressive ratio schedule (5, 12, 33, 100, 180, 340, 540, 835, 1220, 1660, and 2275 'mouse' clicks; identical schedule for both options and experimental sessions). Units were $0.25 money and 1 cigarette puff. Earned cigarette puffs were smoked at the end of the task and earned money was applied to the subject's study payment. The task was completed between 2:30pm and 3pm for each session.
Measured: 30 minutes
Secondary outcomes (2)
Letter 2-back task
Participants completed 5 blocks of a letter 2-back working memory task during proton functional magnetic resonance spectroscopy data acquisition from the left dorsolateral prefrontal cortex. The 2-back task consisted of a neurochemistry normalization period (passive viewing of a 3Hz flashing checkerboard; 208s) and alternating periods of passive visual fixation (centered fixation cross; 32s) and letter 2-back (64s; 4s instructions ['2-back'], 20 letters [3s/letter; 500ms on screen; 2500ms blank screen], 6 target letters). Changes in neurochemistry as quantified using LCModel were the primary outcome variable. 2-back response accuracy (% correct) and response latency (ms) were secondary outcomes.
Measured: 12 minutes
Cigarette-cued letter N-back task
Participants completed a neutral image vs. cigarette smoking-related image cued letter N-back task during functional magnetic resonance imaging acquisition. The task consisted of pseudo-randomly ordered blocks of 0-, 1-, and 2-back with either cigarette cues or matched neutral images behind each letter. Two 32s blocks of each task permutation were collected separated by 16s of blank screen (to minimize carry-over effects). Patterns of brain activation throughout the task was the primary outcome measure while N-back response accuracy (% correct) and response latency (ms) were secondary outcomes.
Measured: 15 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2018
- Study start7 Jan 2016
- Primary completion4 Oct 2016
- Study completion4 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cigarette SmokingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Double-blind, placebo-controlled, and randomized cross-over study design. Each subject completed both the placebo and acute stress experimental sessions.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Eric Andrew Woodcock, Wayne State University
- Investigators
- Eric A Woodcock, PhD, Principal investigator, Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03670212
- Sponsor's protocol ID
- 1501013735
- Other IDs
- F31DA040369
- Acronym
- NSS
- Status last verified
- Sep 2018
- First submitted
- 9 Sep 2018
- Last updated
- 13 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cox LS, Tiffany ST, Christen AG. Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine Tob Res. 2001 Feb;3(1):7-16. doi: 10.1080/14622200020032051.
PubMed 11260806Spielberger CD. Assessment of state and trait anxiety: Conceptual and methodological issues. Southern Psychologist 2(4): 6-16, 1985.
Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.
PubMed 3397865Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986 Mar;43(3):289-94. doi: 10.1001/archpsyc.1986.01800030107013.
PubMed 3954551
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuropharmacological Investigation of Frontostriatal Network Function and Nicotine Seeking Behavior in Current Smokers
- ClinicalTrials.gov ID
- NCT03670212
- Acronym / sponsor ID
- NSS / 1501013735
- Conditions
- Cigarette Smoking
- Keywords
- cigarette smoking, acute stress, executive function, craving, nicotine seeking, relapse, excitatory neural activity, glutamate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 7 Jan 2016 (actual)
- Primary completion
- 4 Oct 2016 (actual)
- Study completion
- 4 Oct 2016 (actual)
- First posted
- 13 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, 21 non-treatment-seeking cigarette smokers were recruited to investigate the effects of acute stress on brain function and nicotine seeking/self-administration behavior.
Detailed description
Non-treatment-seeking cigarette smoking individuals were recruited from the Detroit, MI area. Individuals were screened for cardiovascular, neurological, and psychiatric contraindications. 21 healthy smokers completed two oral pre-treatment experimental sessions (on separate non-consecutive days) in randomized order under double-blind conditions: placebo (lactose) and stress (54mg yohimbine and 10mg hydrocortisone). Yohimbine + hydrocortisone elicit a neurochemical and physiological response that mimics a 'natural' stressor. Placebo and stress sessions were identical and started at 11am. Upon arrival, subject sobriety was confirmed with expired breath alcohol measurement (<.02%). At 11:30am, each subject smoked 6 cigarette puffs (preferred brand; provided by study) over 5 minutes to control for recent nicotine exposure. Throughout each experimental session, subjects periodically completed self-reported measures of cigarette craving, nicotine withdrawal symptoms, affect, and anxiety, and vital signs were measured. Subjects self-administered (swallowed) oral doses of yohimbine (or placebo) at 11:45am and hydrocortisone (or placebo) at 12:15pm. At 1pm, subjects completed a 60-min neuroimaging scan which included: 1) T1-weighted structural scan, 2) proton functional magnetic resonance spectroscopy (fMRS) acquisition from the left prefrontal cortex during a letter 2-back working memory paradigm, and 3) functional magnetic resonance imaging (fMRI) acquisition during an N-back paradigm yoked with cigarette cues. At 2:30pm, subjects completed an 11-trial choice progressive ratio task in which they could earn cigarette puffs (preferred brand; provided by study) or money. At 3pm, subjects self-administered earned cigarette puffs (video monitored). Subjects remained on site until 4pm discharge.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-blind, placebo-controlled, and randomized cross-over study design. Each subject completed both the placebo and acute stress experimental sessions.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Lactose Monohydrate PowderThe placebo compound, Lactose Monohydrate Powder, was encapsulated in generic opaque capsules identical to the capsules used in the acute stress session. During the placebo session, two capsules were self-administered (swallowed) by each subject. At 11:45am, subjects self-administered a capsule containing 54mg of lactose. At 12:15pm, subjects self-administered a capsule containing 10mg of lactose. |
| Acute Stress | Experimental | Drug: Yohimbine Hydrochloride, Drug: HydrocortisoneDuring the acute stress experimental session, subjects self-administered two generic opaque capsules. At 11:45am, subjects self-administered a capsule containing 54mg of Yohimbine Hydrochloride powder. At 12:15pm, subjects self-administered a capsule containing 10mg of Hydrocortisone. |
Who may qualify
- Ages
- 21 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 1) Aged between 21-35 years old, 2) current smokers (expired breath carbon monoxide > 4ppm, self-reported 10+ cigarettes/day, Fagerstrom test for nicotine dependence score > 3, 3) normal seated and resting vital signs (systolic blood pressure 80-160mmHg, diastolic blood pressure 50-90mmHg, and heart rate 50-90 bpm), and 4) normal or corrected-normal vision.
Key exclusion criteria (1 listed)
- 1) Abnormal electrocardiogram (reviewed by licensed cardiologist), 2) magnetic resonance imaging contraindications (e.g. metal implants), 3) medical/neurological contraindications (e.g., diabetes or head trauma), 4) pregnancy (urine test; females only), 5) positive urine test result for opioids, cocaine metabolites, benzodiazepines, barbiturates, or amphetamines, 6) psychiatric contraindications (subject met criteria for current Axis 1 disorder [other than nicotine dependence] as indicated by computerized MINI-6 screen), and 7) self-reported marijuana and/or alcohol use on 15+ days in the past month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Yohimbine HydrochlorideAlso: YOH54mg of yohimbine powder was encapsulated in a generic opaque capsule and swallowed with water. | Drug | Acute Stress |
| HydrocortisoneAlso: HYD10mg hydrocortisone was encapsulated in a generic opaque capsule and swallowed with water. | Drug | Acute Stress |
| Lactose Monohydrate PowderAlso: PlaceboLactose powder was encapsulated in generic opaque capsules identical to those used during the acute stress session. Lactose doses weighed the same as the acute stress session doses (54mg and 10mg, respectively). | Drug | Placebo |
Primary outcome
Cigarette puff vs. money choice task
Time frame: 30 minutes
Participants could earn (via computer mouse 'clicks') money or cigarette puffs (preferred brand; provided by the study) across 11 independent choice trials. At the start of each trial, subjects selected either money or cigarette puffs on a computer screen. After each selection, subjects could earn one unit of that selection by satisfying the computer 'mouse' click requirement. The click requirement increased with each successive unit earned separately for cigarette puffs and money following a progressive ratio schedule (5, 12, 33, 100, 180, 340, 540, 835, 1220, 1660, and 2275 'mouse' clicks; identical schedule for both options and experimental sessions). Units were $0.25 money and 1 cigarette puff. Earned cigarette puffs were smoked at the end of the task and earned money was applied to the subject's study payment. The task was completed between 2:30pm and 3pm for each session.
2 secondary outcomes
Letter 2-back task
Time frame: 12 minutes
Cigarette-cued letter N-back task
Time frame: 15 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Background: PubMed 11260806Cox LS, Tiffany ST, Christen AG. Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine Tob Res. 2001 Feb;3(1):7-16. doi: 10.1080/14622200020032051.
- BackgroundSpielberger CD. Assessment of state and trait anxiety: Conceptual and methodological issues. Southern Psychologist 2(4): 6-16, 1985.
- Background: PubMed 3397865Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.
- Background: PubMed 3954551Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986 Mar;43(3):289-94. doi: 10.1001/archpsyc.1986.01800030107013.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric A Woodcock, PhD principal investigator
Wayne State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Yohimbine Hydrochloride, Hydrocortisone and Lactose Monohydrate Powder in people with Cigarette Smoking, run by Wayne State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cigarette puff vs. money choice task (time frame: 30 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03670212, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.