Attention Deficit Hyperactivity Disorder (ADHD) Smoking Cessation Study

Not Applicable

Completed

Conditions: Attention Deficit Hyperactivity Disorder
Nicotine Dependence

Interventions: Drug: Transdermal Nicotine Patch
Drug: Placebo
Drug: Lis-dexamphetamine (Vyvanse)

Registration Number: NCT00736255

Lead Sponsor: Duke University

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vyvanse and transdermal nicotine patch	Transdermal Nicotine Patch	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	Transdermal Nicotine Patch	The second group will receive matching placebo and NRT after the quit date.
Placebo and transdermal nicotine patch	Placebo	The second group will receive matching placebo and NRT after the quit date.
Vyvanse and transdermal nicotine patch	Lis-dexamphetamine (Vyvanse)	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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)