Clinical trial NCT00736255: Attention Deficit Hyperactivity Disorder (ADHD) Smoking Cessation Study
Official title: Lis-dexamphetamine (LDX/SPD489)as a Treatment for Smoking Cessation in Nicotine Dependent Individuals With ADHD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Attention Deficit Hyperactivity Disorder
Nicotine Dependence
Keywords: ADHD
Smoking
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Shire
First posted: 2008-08-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 4 weeks
Secondary outcomes:
measure: Smoking Rates
timeFrame: 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)
measure: Continuous Performance Test (CPT) Commission Errors
timeFrame: 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)
measure: Continuous Performance Test (CPT) Reaction Time Standard Error
timeFrame: 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)
measure: ADHD Conners' Adult ADHD Rating Scales (CAARS) Self-Report and Observer Short Forms
timeFrame: Randomization, Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28)
measure: N-back Test Proportion Correct Across 4 Load Factors
timeFrame: 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)
measure: Clinician Rated Clinical Global Impressions of Improvement Scale (CGI-I)
timeFrame: Visits 2 (day 7), 4 (day 14), 6 (day 21), 8 (day 28)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Attention Deficit Hyperactivity Disorder (ADHD) Program
state: North Carolina
Study officials:
affiliation: Duke University
name: Scott H Kollins, PhD
role: PRINCIPAL_INVESTIGATOR
References: