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| ID | Type | Description | Link |
|---|---|---|---|
| MIRECC 000000000 | Registry Identifier | Department of Veteran's Affairs | |
| DPMC | Other Identifier | NIDA | |
| R01DA014537 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| US Department of Veterans Affairs | FED |
| National Institute on Drug Abuse (NIDA) | NIH |
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To examine the effects of varenicline on the subjective, physiological and cognitive responses to intravenous nicotine. Varenicline is a partial nicotine agonist and it is approved as a treatment for smoking cessation. We predict that varenicline treatment will modify subjective, physiological and cognitive responses to IV nicotine.
This will be a 2-4 week double-blind, placebo-controlled study. Twenty four male and female smokers will have two 4-day treatment periods, in which they will be randomized to varenicline (1 mg/day) or placebo. During the first 3 days of each treatment period, smokers will have daily clinic visits and receive their study medication. On Day 4, subjects will come to the laboratory, where they will receive ascending doses of intravenous (IV) nicotine (0.1, 0.4, and 0.7 mg per 70kg). This procedure will allow accurate assessment of varenicline effects on the subjective, physiological and cognitive responses to nicotine. Following a washout period, subjects will be crossed over to the alternative treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo First, varenicline, + IV Nic | Experimental | Subjects received a Placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg).After a minimum of a 5 day washout subjects then received varenicline tablet (1mg). once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1,0.4,0.7 mg per 70kg). |
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| Varenicline first, placebo, + IV Nic | Experimental | Subjects received Varenicline tablet (1 mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg). After a washout of a minimum of 5 days subjects then received placebo tablet for per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1,0.4,, and 0.7mg per 70 kg). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Varenicline | Drug | Varenicline (1 mg per day) given for 4 days prior to laboratory session |
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| Measure | Description | Time Frame |
|---|---|---|
| Subjective Responses to Intravenous Nicotine | The Drug Effects Questionaire( DEQ) is a 7-item psychometric that measures the following subjective categories: 'drug strength',' high', 'feels stimulated', 'good effects', 'bad effects', 'head rush', and 'like the drug'. Smokers rated each item on a 100 millimeter scale from "not at all" (a score of 0) to "extremely" with a maximum score of 100. | 30 minutes after each nicotine infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Reaction Time (RT) on Modified Stroop Task. | A Modified stroop task was used to assess attentional responses to smoking and negative affect cues. Cues were presented as blue, red or green text. Subjects completed 2 counterbalanced blocks (60 trials per block). One block contained smoking cues and neutral cues. The other block contained negative affect cues and a different set of matched neutral cues. The 2 blocks were administered twice during each experimental session - prior to nicotine infusion, and 30 mins after the last nicotine infusion (2 hrs and 45 mins after medication dosing). The Stroop effect is a differential RT when identifying the colors of words presented as neutral cues vs. emotional cues (i.e. smoking or negative affect cues). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mehmet Sofuoglu, M.D., Ph.D. | Yale University Associate Professor | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Veterans Affairs Hospital | West Haven | Connecticut | 06516 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19693492 | Result | Sofuoglu M, Herman AI, Mooney M, Waters AJ. Varenicline attenuates some of the subjective and physiological effects of intravenous nicotine in humans. Psychopharmacology (Berl). 2009 Nov;207(1):153-62. doi: 10.1007/s00213-009-1643-z. Epub 2009 Aug 20. |
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There was no special pre-assignment procedures for this study. Thirty seven smokers signed a consent form with only 17 randomized. 13 smokers never return to clinic after signing a consent form. 2 smokers were excluded secondary to poor IV access. 5 smokers had dropped out due to a scheduling conflict.
Subjects were recruited from the New Haven Connecticut area through newspaper advertisements and fliers from the summer of 2007 thru the winter of 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo First, Then Varenicline | Subject received a placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending dose of Nicotine (0.1,0.4, and 0.7mg per70kg). After a minimum washout period of 5 days,then subjects received Varenicline (1mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7mg per 70kg). |
| FG001 | Varenicline First, Then Placebo | Subjects received Varenicline (1mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7mg per 70kg).After a minimum of washout period of 5 days, then subjects received a placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending dose of Nicotine (0.1,0.4, and 0.7mg per70kg). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adaptation |
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| First Intervention |
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| Washout Period |
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| Second Intervention |
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37 subjects signed consent. 17 subjects received the first treatment. Five subjects dropped out due to non-compliance with study procedures prior to study completion, and therefore were not included in the analysis. The 12 subjects who completed both interventions were included in the analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | Includes all subjects who completed the study. (The total number of subjects who were enrolled in both arms of the study.) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Mean Reaction Time (RT) on Modified Stroop Task. | A Modified stroop task was used to assess attentional responses to smoking and negative affect cues. Cues were presented as blue, red or green text. Subjects completed 2 counterbalanced blocks (60 trials per block). One block contained smoking cues and neutral cues. The other block contained negative affect cues and a different set of matched neutral cues. The 2 blocks were administered twice during each experimental session - prior to nicotine infusion, and 30 mins after the last nicotine infusion (2 hrs and 45 mins after medication dosing). The Stroop effect is a differential RT when identifying the colors of words presented as neutral cues vs. emotional cues (i.e. smoking or negative affect cues). | Data from all subjects who completed both experimental sessions (nicotine infusion after 4 days of placebo and also 4 days of varneicline, n=12) are presented. RT's < 100 ms, or > 1501 ms were excluded from the analysis (>3 SD's of the mean). The data presented are the mean RT's to identifying word colors under each treatment condition. | Posted | Mean | Standard Deviation | milliseconds | pre-nicotine, and 30 min after last nicotine infusion (Post-Nicotine) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo First, Then Varenicline, First Intervention | Subjects received a placebo tablet once per day for 4 days prior to the first laboratory session (first intervention) where they were given ascending doses of Nicotine (0.1, 0.7mg per 70kg). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mehmet Sofuoglu, M.D., Ph.D. | Yale University | 203-937-4809 | mehmet.sofuoglu@yale.edu |
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| ID | Term |
|---|---|
| D016540 | Smoking Cessation |
| ID | Term |
|---|---|
| D015438 | Health Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000068580 | Varenicline |
| D000073893 | Sugars |
| D009538 | Nicotine |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Sugar Pill |
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| IV Nic | Drug | IV Nicotine given during the laboratory session following 4 days of exposure to the study medication (varenicline or placebo). This nicotine was given during each laboratory session which followed the 4 days of exposure to either placebo then varenicline or varenicline then placebo. |
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| pre-nicotine, and 30 min after last nicotine infusion (Post-Nicotine) |
| Cotinine Levels | Subject Cotinine Levels before each laboratory session. | Before each laboratory session on day 5 |
| Heart Rate | The average peak change (change score = maximum post dose score minus predose baseline) in heart rate was calculated. | 30 minutes after each nicotine infusion |
| Changes in Systolic and Diastolic Blood Pressure | The average peak change (change score = maximum post dose score minus predose baseline) in systolic and diastolic blood pressure after nicotine infusion. | 30 minutes after each nicotine infusion |
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| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| ID | Title | Description |
|---|
| OG000 | Placebo, Pre-Nicotine | Mean reaction time during modified Stroop task under the placebo condition and prior to the nicotine infusions. |
| OG001 | Placebo, Post-Nicotine | Mean reaction time during modified Stroop task under the placebo condition and 30 minutes after the nicotine infusions. |
| OG002 | Varenicline, Pre-Nicotine | Mean reaction time during modified Stroop task under the varenicline condition prior to the nicotine infusions. |
| OG003 | Varenicline, Post-Nicotine | Mean reaction time during modified Stroop task under the varenicline condition and 30 minutes after the nicotine infusions. |
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| Secondary | Cotinine Levels | Subject Cotinine Levels before each laboratory session. | Subjects finishing the complete study. (n=12) | Posted | Mean | Standard Deviation | ng/mL | Before each laboratory session on day 5 |
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| Primary | Subjective Responses to Intravenous Nicotine | The Drug Effects Questionaire( DEQ) is a 7-item psychometric that measures the following subjective categories: 'drug strength',' high', 'feels stimulated', 'good effects', 'bad effects', 'head rush', and 'like the drug'. Smokers rated each item on a 100 millimeter scale from "not at all" (a score of 0) to "extremely" with a maximum score of 100. | All participants who complete all interventions. | Posted | Mean | Standard Error | millimeters | 30 minutes after each nicotine infusion |
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| Secondary | Heart Rate | The average peak change (change score = maximum post dose score minus predose baseline) in heart rate was calculated. | Changes in heart rate, systolic and diastolic blood pressure during the experimental sessions were analyzed on all subjects who completed both experimental sessions (n=12). | Posted | Mean | Standard Error | beats per minute | 30 minutes after each nicotine infusion |
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| Secondary | Changes in Systolic and Diastolic Blood Pressure | The average peak change (change score = maximum post dose score minus predose baseline) in systolic and diastolic blood pressure after nicotine infusion. | Changes in heart rate, systolic and diastolic blood pressure during the experimental sessions were analyzed on all subjects who completed both experimental sessions (n=12). | Posted | Mean | Standard Error | mm Hg | 30 minutes after each nicotine infusion |
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| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Varenicline First, Then Placebo, First Intervention | Subjects received varenicline once per day for 4 days prior to the first laboratory session (first intervention) where they were given ascending doses of Nicotine (0.1, 0.7mg per 70kg). | 0 | 8 | 0 | 8 |
| EG002 | Adaptation - Placebo First, Then Varenicline | Subjects randomized to the 'Placebo first' condition participated in a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, 0.7mg per 70 kg) to assess tolerability prior to the study medication intervention. | 0 | 9 | 0 | 9 |
| EG003 | Adaptation - Varenicline First, Then Placebo | Subjects randomized to the 'Varenicline first' condition first received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, 0.7mg per 70 kg) to assess tolerability before receiving the study medication. | 0 | 8 | 0 | 8 |
| EG004 | Placebo First, Then Varenicline, Second Intervention | Subjects crossed-over from the first intervention and received varenicline once per day for 4 days prior to the second laboratory session (second intervention) where they were given ascending doses of Nicotine (0.1, 0.7mg per 70kg). | 0 | 8 | 0 | 8 |
| EG005 | Varenicline First, Then Placebo, Second Intervention | Subjects crossed-over from the first intervention (varenicline) and received placebo once per day for 4 days prior to the second laboratory session (second intervention) where they were given ascending doses of Nicotine (0.1, 0.7mg per 70kg). | 0 | 4 | 0 | 4 |
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| D011810 | Quinoxalines |
| D002241 | Carbohydrates |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Head Rush |
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| Feels Stimulated |
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| Drug Strength |
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| Bad Effects |
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| Good Effects |
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| Like the Drug |
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| No |
| Superiority or Other |
| Diastolic Blood Pressure |
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