Attention Deficit Hyperactivity Disorder (ADHD) Smoking Cessation Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Lis-dexamphetamine (LDX/SPD489)as a Treatment for Smoking Cessation in Nicotine Dependent Individuals With ADHD

Conditions
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Attention Deficit Hyperactivity Disorder, Nicotine Dependence

Intervention / Treatment
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* Drug: Transdermal Nicotine Patch
* Drug: Lis-dexamphetamine (Vyvanse)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vyvanse and transdermal nicotine patch<br>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. | Drug: Transdermal Nicotine Patch<br>* 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.<br>* Other names: Nicotine Patch;Drug: Lis-dexamphetamine (Vyvanse)<br>* 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.<br>* Other names: LDX and Transdermal Nicotine Patch;|
| Placebo Comparator: Placebo and transdermal nicotine patch<br>The second group will receive matching placebo and NRT after the quit date. | Drug: Transdermal Nicotine Patch<br>* 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.<br>* Other names: Nicotine Patch;Drug: Placebo<br>* Subjects on this arm will receive matching placebo, along with Nicotine Replacement Therapy.<br>* Other names: Placebo and Transdermal Nicotine Patch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, Smoking