Attention Deficit Hyperactivity Disorder, Nicotine Dependence
Conditions
Keywords
ADHD, Smoking
Brief summary
The overall goal of the present project is to investigate whether lisdexamphetamine (LDX; Vyvanse) is an effective adjunct to nicotine replacement therapy (NRT) to promote smoking cessation in patients with comorbid Attention Deficit Hyperactivity Disorder (ADHD) and nicotine dependence. The investigators hypothesized initially that smokers with ADHD who are optimized to a dose of LDX prior to quitting smoking and who remain on this dose of medication after quitting will remain abstinent longer than patients who are treated with placebo before and after quitting.However due to recent key issues that have arisen showing that initiation of stimulant treatment while subjects are actively smoking may facilitate increased smoking, and given that the study was still in the very early stage of study execution, the investigators revised the study design to use an empirically validated pretreatment approach with NRT and to initiate LDX treatment on the first post quit date in order to reduce the withdrawal symptoms that accompany smoking cessation. The overall rationale for this revised study design remains similar to the original.
Detailed description
This will be a 2-group, parallel, placebo-controlled, double blind study. Regular, nicotine dependent individuals with ADHD will receive NRT pretreatment for 2 weeks prior to an identified quit date.At the quit date, subjects will be randomized into one of two groups. * The first group will begin treatment for 1 week with LDX 30 mg and then will be titrated up to 50mg and 70mg if tolerated. Subjects will continue on the highest tolerated dose until the 4th week. Concurrently subjects will receive transdermal NRT, 21 mg at week one, 14 mg at week 2 and 7 mg at weeks 3 and 4. * The second group will receive matching placebo and transdermal NRT after the quit date. Participants will attend a total of 16 visits over a period of 7-11 weeks. The primary outcome measure for this study will be the proportion of individuals in each group who report 4 weeks continuous smoking abstinence verified by both Carbon Monoxide (CO) levels and salivary cotinine, measured at Visit 5. It is hypothesized that the group co-treated with LDX will have a significantly higher proportion of individuals who remain abstinent across the 4 weeks measured every other day. Inclusion Criteria: * Aged 18-50 years * Meet DSM-IV criteria (Diagnostic and Statistical manual of mental Disorders Version 4) for ADHD, any subtype; assessed using the Conners Adult ADHD Interview for DSM (CAADID) * Meet DSM-IV criteria for nicotine dependence as verified by afternoon expired CO levels of \>15 parts per million (PPM) and self-report of smoking \>10 cigarettes/day * Free from major medical problems and deemed healthy by the study physician * Not currently receiving medication for ADHD or other psychiatric disorders. If a patient is screened as is currently receiving medication for ADHD, they may be enrolled, provided they washout of their current medication for an appropriate length of time. * No contraindications for treatment with either LDX or transdermal nicotine Exclusion Criteria: * DSM-IV Axis I or Axis II disorders that require additional pharmacological treatment or otherwise would interfere with participation in the present study * History of known cardiovascular disease, clinically significant hypertension, or other cardiovascular risk factors which, in the opinion of the study physician, would contraindicate treatment * BMI (Body Mass Index) \> 35
Interventions
DRUGTransdermal Nicotine Patch
All subjects will lreceive transdermal nicotine patch during beginning at Visit 0 (quit smoke date). The dose will be tapered down from 21 mg to 14mg after week 1,vthen to 7 mg after week 2. Subjects will remain at 7mg until the 4th week.
DRUGLis-dexamphetamine (Vyvanse)
Subjects on this arm will receive Lis-dexamphetamine day after the identified quit date. All subject will start with 30mg once a day and will be titrated up to 50mg then to 70mg over a 3 week period to reach an optimized dose. They will then be maintained on this optimized dose until the 4th week.
DRUGPlacebo
Subjects on this arm will receive matching placebo, along with Nicotine Replacement Therapy.
Sponsors
Shire
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Attention Deficit Hyperactivity Disorder(ADHD) diagnosis * smokes at least \> 10 cigarettes per day * no major medical problems * no contraindications to treatment with either LDX or transdermal nicotine
Exclusion criteria
* other psychiatric conditions that require medication * history of cardiovascular disease, clinically significant hypertension * Body Mass index (BMI) \> 35
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects in Each Treatment Group Exhibiting Sustained, 4-week Smoking Abstinence, Defined as CO Levels <= 4 Ppm for Each Post-quit Study Visit. | 4 weeks | The primary outcome measure was the proportion of subjects in each treatment group exhibiting sustained, 4-week smoking abstinence, defined as CO levels \<= 4 ppm for each post-quit study visit. Subjects who dropped from the study for any reason were considered to have lapsed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Continuous Performance Test (CPT) Commission Errors | Randomization, Visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28) | The CPT is a measure of both vigilance/sustained attention and response inhibition, has good normative data and has been shown to be sensitive to the effects of stimulants. Reaction time variability and commission errors - measures of attentional control and response inhibition have been shown to be sensitive in discriminating individuals with ADHD on active medication versus placebo. |
| Continuous Performance Test (CPT) Reaction Time Standard Error | Randomization, Visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28) | The CPT is a measure of both vigilance/sustained attention and response inhibition, has good normative data and has been shown to be sensitive to the effects of stimulants. Reaction time variability and commission errors - measures of attentional control and response inhibition have been shown to be sensitive in discriminating individuals with ADHD on active medication versus placebo. |
| Smoking Rates | Randomization, visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28) | Smoking rates, measured as self-reported cigarettes/day. |
| N-back Test Proportion Correct Across 4 Load Factors | Randomization, Visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28) | This is measured by the N-Back test, a cognitive functioning, including working memory test. The test is designed with 4 Load Factors, where the current stimulus matches the one from 'n' steps back or prior in the sequence. The load factor n is adjusted so there is a 'O-back' (i.e. 'n-0'), '1-back' (i.e. 'n-1'), '2-back' (i.e. 'n-2'), and '3-back' (i.e. 'n-3'). When the correct stimulus appears on the screen, the participant then responds on the computer. Missing the stimulus decreases the proportion correct. |
| Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28) | Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. 1-Very Much Improved through 7-Very Much Worse. |
| ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Randomization, Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28) | T-scores derived from compiled ADHD symptoms from two forms. Specifically the t-scores for the DSM-IV Total subscale, representing ADHD symptoms. This is conducted by the participant and clinician at randomization, visits 2 and 4 (i.e. dose titration visits), Visit 6 (i.e. monitoring visit), and Visit 8 (i.e. final/end of study visit). The following describes severity of the ADHD symptoms (based upon T-Score): 70+ = Very Much Above Average 66-70 = Much Above Average 61-65 = Above Average 56-60 = Slightly Above Average 45-55 = Average 30-44 = Below Average (Low scores are good) |
Countries
United States
Participant flow
Recruitment details
Recruitment ended in March 2011 at the Duke.A total of 59 subjects were screened. 24 did not pass screening while 35 were eligible. Of the 35 screen passers, 32 were randomized to receive either LDX or placebo, 3 were withdrawn prior to randomization. Of the 32 randomized, 17 received LDX and 15 received placebo. 14 completed on each arm.
Pre-assignment details
There were 24 screen fails. Reason for Screen Fails include:Did not complete screening - 2,Carbon monoxide too low - 3,Positive Urine drug screen - 3,Physical health reasons - 5,Psychiatric comorbidity - 11
Participants by arm
| Arm | Count |
|---|---|
| LDX and NRT • The first group will receive LDX/SPD489 titrated up to 70 mg qd for 4 weeks after the identified quit date. Subjects will continue to receive NRT 21 mg at week 1 post quit date, then 14mg at week 2 post quit date and 7 at weeks 3 and 4 post quit date. | 17 |
| NRT and Placebo The second group will receive matching placebo and NRT after the quit date. | 15 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Non-compliance | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | NRT and Placebo | LDX and NRT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 17 Participants | 32 Participants |
| Age, Continuous | 33.5 years STANDARD_DEVIATION 9.1 | 29.6 years STANDARD_DEVIATION 8.4 | 31 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 15 participants | 17 participants | 32 participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 6 Participants | 11 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 17 | 12 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 15 |
Outcome results
Primary
The Number of Subjects in Each Treatment Group Exhibiting Sustained, 4-week Smoking Abstinence, Defined as CO Levels <= 4 Ppm for Each Post-quit Study Visit.
The primary outcome measure was the proportion of subjects in each treatment group exhibiting sustained, 4-week smoking abstinence, defined as CO levels \<= 4 ppm for each post-quit study visit. Subjects who dropped from the study for any reason were considered to have lapsed.
Time frame: 4 weeks
Population: Subjects exhibiting sustained 4 week smoking abstinence defined as CO levels \<= 4ppm for each post quit study visit were analyzed for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDX and NRT | The Number of Subjects in Each Treatment Group Exhibiting Sustained, 4-week Smoking Abstinence, Defined as CO Levels <= 4 Ppm for Each Post-quit Study Visit. | 5 participants |
| NRT and Placebo | The Number of Subjects in Each Treatment Group Exhibiting Sustained, 4-week Smoking Abstinence, Defined as CO Levels <= 4 Ppm for Each Post-quit Study Visit. | 3 participants |
Comparison: Null Hypothesis:LDX and NRT will not facilitate smoking cessation compared to NRT and placebo.~Alternate Hypothesis: LDX and NRT will facilitate smoking cessation compared to NRT and placebo.~This is a one tailed, proof of concept study so there is no formal power analysis, however if we see a signal for treatment effect, we would like to do further investigation by conducting a separate trial.p-value: 0.54Chi-squared
Secondary
ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms
T-scores derived from compiled ADHD symptoms from two forms. Specifically the t-scores for the DSM-IV Total subscale, representing ADHD symptoms. This is conducted by the participant and clinician at randomization, visits 2 and 4 (i.e. dose titration visits), Visit 6 (i.e. monitoring visit), and Visit 8 (i.e. final/end of study visit). The following describes severity of the ADHD symptoms (based upon T-Score): 70+ = Very Much Above Average 66-70 = Much Above Average 61-65 = Above Average 56-60 = Slightly Above Average 45-55 = Average 30-44 = Below Average (Low scores are good)
Time frame: Randomization, Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDX and NRT | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 2 (day 7) | 63.07 T-score on a scale | Standard Deviation 11.48 |
| LDX and NRT | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 6 (day 21) | 52.83 T-score on a scale | Standard Deviation 17.07 |
| LDX and NRT | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Randomization (Visit 0) | 67.13 T-score on a scale | Standard Deviation 9.75 |
| LDX and NRT | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 8 (day 28) | 54.00 T-score on a scale | Standard Deviation 15.33 |
| LDX and NRT | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 4 (day 14) | 58.62 T-score on a scale | Standard Deviation 13.18 |
| NRT and Placebo | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 8 (day 28) | 61.92 T-score on a scale | Standard Deviation 11.46 |
| NRT and Placebo | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 2 (day 7) | 64.62 T-score on a scale | Standard Deviation 8.69 |
| NRT and Placebo | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 4 (day 14) | 65.25 T-score on a scale | Standard Deviation 9.85 |
| NRT and Placebo | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Visit 6 (day 21) | 63.42 T-score on a scale | Standard Deviation 12.7 |
| NRT and Placebo | ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms | Randomization (Visit 0) | 68.08 T-score on a scale | Standard Deviation 7.48 |
Secondary
Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I)
Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. 1-Very Much Improved through 7-Very Much Worse.
Time frame: Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDX and NRT | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 2 (day 7) CGI-I | 2.88 score on a scale | Standard Deviation 0.89 |
| LDX and NRT | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 4 (day 14) CGI-I | 2.73 score on a scale | Standard Deviation 1.03 |
| LDX and NRT | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 6 (day 21) CGI_I | 2.29 score on a scale | Standard Deviation 1.2 |
| LDX and NRT | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 8 (day 28) CGI-I | 2.00 score on a scale | Standard Deviation 1.24 |
| NRT and Placebo | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 8 (day 28) CGI-I | 3.15 score on a scale | Standard Deviation 0.99 |
| NRT and Placebo | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 2 (day 7) CGI-I | 3.50 score on a scale | Standard Deviation 0.76 |
| NRT and Placebo | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 6 (day 21) CGI_I | 3.31 score on a scale | Standard Deviation 1.18 |
| NRT and Placebo | Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I) | Visit 4 (day 14) CGI-I | 3.38 score on a scale | Standard Deviation 0.77 |
Secondary
Continuous Performance Test (CPT) Commission Errors
The CPT is a measure of both vigilance/sustained attention and response inhibition, has good normative data and has been shown to be sensitive to the effects of stimulants. Reaction time variability and commission errors - measures of attentional control and response inhibition have been shown to be sensitive in discriminating individuals with ADHD on active medication versus placebo.
Time frame: Randomization, Visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 1 (day 4) | 13.29 Errors of Commission | Standard Deviation 9.64 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 5 (day 18) | 15.00 Errors of Commission | Standard Deviation 7.67 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 3 (day 11) | 14.50 Errors of Commission | Standard Deviation 8.91 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 6 (day 21) | 12.36 Errors of Commission | Standard Deviation 10.43 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 2 (day 7) | 13.44 Errors of Commission | Standard Deviation 9.14 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 7 (day 25) | 14.64 Errors of Commission | Standard Deviation 9.2 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 4 (day 14) | 13.13 Errors of Commission | Standard Deviation 8.33 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Visit 8 (day 28) | 14.92 Errors of Commission | Standard Deviation 10.8 |
| LDX and NRT | Continuous Performance Test (CPT) Commission Errors | Randomization (Visit 0) | 15.29 Errors of Commission | Standard Deviation 10.58 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 8 (day 28) | 11.23 Errors of Commission | Standard Deviation 9.77 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Randomization (Visit 0) | 12.43 Errors of Commission | Standard Deviation 9.37 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 1 (day 4) | 10.71 Errors of Commission | Standard Deviation 8.62 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 2 (day 7) | 10.86 Errors of Commission | Standard Deviation 8.7 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 3 (day 11) | 10.79 Errors of Commission | Standard Deviation 7.52 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 4 (day 14) | 11.08 Errors of Commission | Standard Deviation 9.29 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 5 (day 18) | 11.15 Errors of Commission | Standard Deviation 9.2 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 6 (day 21) | 12.15 Errors of Commission | Standard Deviation 8.12 |
| NRT and Placebo | Continuous Performance Test (CPT) Commission Errors | Visit 7 (day 25) | 11.77 Errors of Commission | Standard Deviation 6.98 |
Secondary
Continuous Performance Test (CPT) Reaction Time Standard Error
The CPT is a measure of both vigilance/sustained attention and response inhibition, has good normative data and has been shown to be sensitive to the effects of stimulants. Reaction time variability and commission errors - measures of attentional control and response inhibition have been shown to be sensitive in discriminating individuals with ADHD on active medication versus placebo.
Time frame: Randomization, Visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 2 (day 7) | 5.42 Reaction time in seconds | Standard Deviation 3.45 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 5 (day 18) | 5.54 Reaction time in seconds | Standard Deviation 2.77 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 1 (day 4) | 5.52 Reaction time in seconds | Standard Deviation 3.44 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 6 (day 21) | 4.64 Reaction time in seconds | Standard Deviation 2.28 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 3 (day 11) | 4.97 Reaction time in seconds | Standard Deviation 2.71 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 7 (day 25) | 5.29 Reaction time in seconds | Standard Deviation 2.73 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Randomization (Visit 0) | 5.37 Reaction time in seconds | Standard Deviation 1.93 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 8 (day 28) | 4.86 Reaction time in seconds | Standard Deviation 2.23 |
| LDX and NRT | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 4 (day 14) | 4.83 Reaction time in seconds | Standard Deviation 2.55 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 8 (day 28) | 5.08 Reaction time in seconds | Standard Deviation 2.04 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Randomization (Visit 0) | 4.61 Reaction time in seconds | Standard Deviation 1.31 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 1 (day 4) | 4.68 Reaction time in seconds | Standard Deviation 1.44 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 2 (day 7) | 5.05 Reaction time in seconds | Standard Deviation 1.81 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 3 (day 11) | 5.01 Reaction time in seconds | Standard Deviation 1.46 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 4 (day 14) | 4.79 Reaction time in seconds | Standard Deviation 1.71 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 5 (day 18) | 5.15 Reaction time in seconds | Standard Deviation 1.71 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 6 (day 21) | 4.97 Reaction time in seconds | Standard Deviation 1.62 |
| NRT and Placebo | Continuous Performance Test (CPT) Reaction Time Standard Error | Visit 7 (day 25) | 5.73 Reaction time in seconds | Standard Deviation 2.01 |
Secondary
N-back Test Proportion Correct Across 4 Load Factors
This is measured by the N-Back test, a cognitive functioning, including working memory test. The test is designed with 4 Load Factors, where the current stimulus matches the one from 'n' steps back or prior in the sequence. The load factor n is adjusted so there is a 'O-back' (i.e. 'n-0'), '1-back' (i.e. 'n-1'), '2-back' (i.e. 'n-2'), and '3-back' (i.e. 'n-3'). When the correct stimulus appears on the screen, the participant then responds on the computer. Missing the stimulus decreases the proportion correct.
Time frame: Randomization, Visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 2-back _%cor | 0.90 proportion correct to stimuli response | Standard Deviation 0.25 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 1-back _%cor | 0.90 proportion correct to stimuli response | Standard Deviation 0.25 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 3-back _%cor | 0.90 proportion correct to stimuli response | Standard Deviation 0.25 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 2-back _%cor | 0.86 proportion correct to stimuli response | Standard Deviation 0.3 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 0-back _%cor | 1.00 proportion correct to stimuli response | Standard Deviation 0 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 3-back _%cor | 0.84 proportion correct to stimuli response | Standard Deviation 0.14 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 1-back _%cor | 0.98 proportion correct to stimuli response | Standard Deviation 0.08 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 3-back _%cor | 0.81 proportion correct to stimuli response | Standard Deviation 0.28 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 2-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.02 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 2-back _%cor | 0.89 proportion correct to stimuli response | Standard Deviation 0.27 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 3-back _%cor | 0.88 proportion correct to stimuli response | Standard Deviation 0.16 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 0-back _%cor | 0.89 proportion correct to stimuli response | Standard Deviation 0.27 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 0-back _%cor | 0.93 proportion correct to stimuli response | Standard Deviation 0.27 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 2-back _%cor | 0.96 proportion correct to stimuli response | Standard Deviation 0.08 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 1-back _%cor | 0.93 proportion correct to stimuli response | Standard Deviation 0.27 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 1-back _%cor | 0.89 proportion correct to stimuli response | Standard Deviation 0.28 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 2-back _%cor | 0.90 proportion correct to stimuli response | Standard Deviation 0.26 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 3-back _%cor | 0.80 proportion correct to stimuli response | Standard Deviation 0.31 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 3-back _%cor | 0.89 proportion correct to stimuli response | Standard Deviation 0.26 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 2-back _%cor | 0.89 proportion correct to stimuli response | Standard Deviation 0.27 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25) 0-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.03 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 0-back _%cor | 0.95 proportion correct to stimuli response | Standard Deviation 0.23 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25)1-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.03 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 3-back _%cor | 0.84 proportion correct to stimuli response | Standard Deviation 0.3 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25) 2-back _%cor | 0.97 proportion correct to stimuli response | Standard Deviation 0.07 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 0-back _%cor | 0.93 proportion correct to stimuli response | Standard Deviation 0.26 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25) 3-back _%cor | 0.91 proportion correct to stimuli response | Standard Deviation 0.11 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 0-back _%cor | 0.93 proportion correct to stimuli response | Standard Deviation 0.26 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 0-back _%cor | 0.93 proportion correct to stimuli response | Standard Deviation 0.23 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 1-back _%cor | 0.94 proportion correct to stimuli response | Standard Deviation 0.15 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 1-back _%cor | 0.98 proportion correct to stimuli response | Standard Deviation 0.03 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 1-back _%cor | 0.91 proportion correct to stimuli response | Standard Deviation 0.26 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 2-back _%cor | 0.92 proportion correct to stimuli response | Standard Deviation 0.27 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 1-back _%cor | 0.90 proportion correct to stimuli response | Standard Deviation 0.26 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 3-back _%cor | 0.91 proportion correct to stimuli response | Standard Deviation 0.13 |
| LDX and NRT | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 0-back _%cor | 0.96 proportion correct to stimuli response | Standard Deviation 0.12 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 3-back _%cor | 0.84 proportion correct to stimuli response | Standard Deviation 0.21 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 0-back _%cor | 1.00 proportion correct to stimuli response | Standard Deviation 0 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 1-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.03 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 2-back _%cor | 0.95 proportion correct to stimuli response | Standard Deviation 0.09 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Randomization (Visit 0) 3-back _%cor | 0.80 proportion correct to stimuli response | Standard Deviation 0.29 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 0-back _%cor | 1.00 proportion correct to stimuli response | Standard Deviation 0 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 1-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.02 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 2-back _%cor | 0.96 proportion correct to stimuli response | Standard Deviation 0.09 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 1 (day 4) 3-back _%cor | 0.83 proportion correct to stimuli response | Standard Deviation 0.18 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 0-back _%cor | 0.92 proportion correct to stimuli response | Standard Deviation 0.27 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 1-back _%cor | 0.95 proportion correct to stimuli response | Standard Deviation 0.11 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 2-back _%cor | 0.92 proportion correct to stimuli response | Standard Deviation 0.13 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 2 (day 7) 3-back _%cor | 0.81 proportion correct to stimuli response | Standard Deviation 0.27 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 0-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.02 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 1-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.02 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 2-back _%cor | 0.95 proportion correct to stimuli response | Standard Deviation 0.1 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 3 (day 11) 3-back _%cor | 0.90 proportion correct to stimuli response | Standard Deviation 0.14 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 0-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.02 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 1-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.03 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 2-back _%cor | 0.95 proportion correct to stimuli response | Standard Deviation 0.12 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 4 (day 14) 3-back _%cor | 0.89 proportion correct to stimuli response | Standard Deviation 0.15 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 0-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.03 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 1-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.02 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 2-back _%cor | 0.98 proportion correct to stimuli response | Standard Deviation 0.08 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 5 (day 18) 3-back _%cor | 0.92 proportion correct to stimuli response | Standard Deviation 0.16 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 0-back _%cor | 1.00 proportion correct to stimuli response | Standard Deviation 0 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 1-back _%cor | 0.98 proportion correct to stimuli response | Standard Deviation 0.03 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 2-back _%cor | 0.96 proportion correct to stimuli response | Standard Deviation 0.09 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 6 (day 21) 3-back _%cor | 0.87 proportion correct to stimuli response | Standard Deviation 0.15 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25) 0-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.04 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25)1-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.03 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25) 2-back _%cor | 0.95 proportion correct to stimuli response | Standard Deviation 0.12 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 7 (day 25) 3-back _%cor | 0.88 proportion correct to stimuli response | Standard Deviation 0.15 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 0-back _%cor | 0.99 proportion correct to stimuli response | Standard Deviation 0.02 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 1-back _%cor | 0.98 proportion correct to stimuli response | Standard Deviation 0.05 |
| NRT and Placebo | N-back Test Proportion Correct Across 4 Load Factors | Visit 8 (day 28) 2-back _%cor | 0.95 proportion correct to stimuli response | Standard Deviation 0.09 |
Secondary
Smoking Rates
Smoking rates, measured as self-reported cigarettes/day.
Time frame: Randomization, visits 1 (day 4), 2 (day 7), 3 (day 11), 4 (day 14), 5 (day 18), 6 (day 21), 7 (day 25), 8 (day 28)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDX and NRT | Smoking Rates | Randomization (Visit 0) | 6.43 Cigarettes smoked per day | Standard Error 1.38 |
| LDX and NRT | Smoking Rates | Visit 4 (day 14) | 2.98 Cigarettes smoked per day | Standard Error 1.31 |
| LDX and NRT | Smoking Rates | Visit 2 (day 7) | 3.16 Cigarettes smoked per day | Standard Error 1.1 |
| LDX and NRT | Smoking Rates | Visit 6 (day 21) | 3.94 Cigarettes smoked per day | Standard Error 1.59 |
| LDX and NRT | Smoking Rates | Visit 1 (day 4) | 3.90 Cigarettes smoked per day | Standard Error 1.28 |
| LDX and NRT | Smoking Rates | Visit 7 (day 25) | 4.38 Cigarettes smoked per day | Standard Error 1.69 |
| LDX and NRT | Smoking Rates | Visit 3 (day 11) | 2.75 Cigarettes smoked per day | Standard Error 1.12 |
| LDX and NRT | Smoking Rates | Visit 8 (day 28) | 4.15 Cigarettes smoked per day | Standard Error 1.58 |
| LDX and NRT | Smoking Rates | Visit 5 (day 18) | 3.08 Cigarettes smoked per day | Standard Error 1.45 |
| NRT and Placebo | Smoking Rates | Visit 8 (day 28) | 2.91 Cigarettes smoked per day | Standard Error 1.07 |
| NRT and Placebo | Smoking Rates | Visit 5 (day 18) | 2.92 Cigarettes smoked per day | Standard Error 1 |
| NRT and Placebo | Smoking Rates | Randomization (Visit 0) | 8.14 Cigarettes smoked per day | Standard Error 1.79 |
| NRT and Placebo | Smoking Rates | Visit 1 (day 4) | 2.59 Cigarettes smoked per day | Standard Error 1.02 |
| NRT and Placebo | Smoking Rates | Visit 2 (day 7) | 1.83 Cigarettes smoked per day | Standard Error 0.84 |
| NRT and Placebo | Smoking Rates | Visit 3 (day 11) | 2.23 Cigarettes smoked per day | Standard Error 0.94 |
| NRT and Placebo | Smoking Rates | Visit 4 (day 14) | 2.10 Cigarettes smoked per day | Standard Error 0.74 |
| NRT and Placebo | Smoking Rates | Visit 6 (day 21) | 2.67 Cigarettes smoked per day | Standard Error 0.98 |
| NRT and Placebo | Smoking Rates | Visit 7 (day 25) | 2.33 Cigarettes smoked per day | Standard Error 0.84 |