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| ID | Type | Description | Link |
|---|---|---|---|
| SPD489-607 | Other Grant/Funding Number | Shire Pharmaceuticals |
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| Name | Class |
|---|---|
| Shire | INDUSTRY |
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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.
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.
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:
Exclusion Criteria:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vyvanse and transdermal nicotine patch | Experimental | 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. |
|
| Placebo and transdermal nicotine patch | Placebo Comparator | The second group will receive matching placebo and NRT after the quit date. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transdermal Nicotine Patch | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Smoking Rates | Smoking rates, measured as self-reported cigarettes/day. | 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) |
| Continuous Performance Test (CPT) Commission Errors |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Scott H Kollins, PhD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke Attention Deficit Hyperactivity Disorder (ADHD) Program | Durham | North Carolina | 27705 | United States |
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
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | NRT and Placebo | The second group will receive matching placebo and NRT after the quit date. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | NRT and Placebo |
| 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 | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Subjects exhibiting sustained 4 week smoking abstinence defined as CO levels <= 4ppm for each post quit study visit were analyzed for the outcome measure. | Posted | Number | participants | 4 weeks |
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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 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | Systematic Assessment |
Limitations of the study: 1. Our sample size was quite small and this can realistically only be considered a pilot trial. 2.We did not collect systematic follow-up data on our sample after the end of treatment.3.the duration of our trial was short.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scott Kollins, PhD | DukeUMC | 9196810014 | kolli001@mc.duke.edu |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| D014029 | Tobacco Use Disorder |
| D012907 | Smoking |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
| D019966 | Substance-Related Disorders |
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| ID | Term |
|---|---|
| D061485 | Tobacco Use Cessation Devices |
| D000069478 | Lisdexamfetamine Dimesylate |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D003913 | Dextroamphetamine |
| D000661 | Amphetamine |
| D000662 | Amphetamines |
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| Lis-dexamphetamine (Vyvanse) | Drug | 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. |
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| Placebo | Drug | Subjects on this arm will receive matching placebo, along with Nicotine Replacement Therapy. |
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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.
| 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) |
| 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. | 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) |
| 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) | Randomization, Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28) |
| 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. | 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) |
| 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. | Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28) |
| Non-compliance |
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The second group will receive matching placebo and NRT after the quit date. |
| BG002 | Total | Total of all reporting groups |
| 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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| Region of Enrollment | Number | participants |
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| OG001 | NRT and Placebo | The second group will receive matching placebo and NRT after the quit date. Placebo and transdermal nicotine patch: Subjects on this arm will receive matching placebo and NRT. |
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| Secondary | Smoking Rates | Smoking rates, measured as self-reported cigarettes/day. | Posted | Mean | Standard Error | Cigarettes smoked per day | 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) |
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| 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. | Posted | Mean | Standard Deviation | Errors of Commission | 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) |
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|
| 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. | Posted | Mean | Standard Deviation | Reaction time in seconds | 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) |
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|
|
| 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) | Posted | Mean | Standard Deviation | T-score on a scale | Randomization, Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28) |
|
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|
| 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. | Posted | Mean | Standard Deviation | proportion correct to stimuli response | 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) |
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| 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. | Posted | Mean | Standard Deviation | score on a scale | Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28) |
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| 0 |
| 17 |
| 15 |
| 17 |
| EG001 | NRT and Placebo | The second group will receive matching placebo and NRT after the quit date. | 0 | 15 | 12 | 15 |
| Acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Restlessness | Psychiatric disorders | Systematic Assessment |
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| Inability to concentrate | Psychiatric disorders | Systematic Assessment |
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| Irritability | Psychiatric disorders | Systematic Assessment |
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| Panic Attack | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Nightmares/Dreams | Psychiatric disorders | Systematic Assessment |
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| Increased Appetite | Psychiatric disorders | Systematic Assessment |
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| Decreased Appetite | Psychiatric disorders | Systematic Assessment |
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| Excessive Thirst | General disorders | Systematic Assessment |
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| Chest tightness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Muscle twitches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Stomach ache | Gastrointestinal disorders | Systematic Assessment |
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| Arm Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Bruxism | Psychiatric disorders | Non-systematic Assessment |
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| Heartburn | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Shaking hands/Tremor | Nervous system disorders | Systematic Assessment |
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| Insomnia | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Chills | General disorders | Systematic Assessment |
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| Skin irritation at NRT patch site | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Dry mouth | General disorders | Non-systematic Assessment |
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| Metallic Taste | Endocrine disorders | Non-systematic Assessment |
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| D064419 | Chemically-Induced Disorders |
| D001519 | Behavior |
| D010627 |
| Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| Visit 4 (day 14) |
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| Visit 8 (day 28) |
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| Visit 6 (day 21) CGI_I |
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| Visit 8 (day 28) CGI-I |
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