Clinical trial NCT03446885
Conditions: Attention Deficit Disorder With Hyperactivity
Sponsor: Gregory Fabiano
Start date: 2018-04-01; Completion date: 2019-08-30
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
There has been little research on the third area of impairment noted in the Diagnostic and Statistical Manual of Mental Disorders - "occupational functioning." Individuals with ADHD experience job-related impairments including a greater likelihood of being unemployed and not enrolled in school and for those that were employed they were in a lower status occupation, relative to typically-developing comparison peers. The current literature on analogue workplace settings and the effects of lisdexamfetamine dimesylate includes office-based tasks similar to school seat work. Unfortunately, this is inconsistent with the typical work environment most common for individuals with disabilities such as ADHD where food preparation is the most common job following high school. Therefore, medication effects in this type of setting, most common for individuals with ADHD entering the workforce, need to be studied. The investigators propose to study workplace behavior in an analogue work setting in a laboratory "pizza place." Individuals with ADHD will participate in an interview with a supervisor each day, have a list of deliveries that need to be managed, deal with situations that require occupational judgment and appropriate customer service, and drive to make deliveries accurately and on-time. These behaviors can be reliably assessed within the laboratory. Twenty young adults will participate in two "workdays" within a randomized, double-blind, placebo-controlled design wherein participants will be administered placebo and .3 mg/kg lisdexamfetamine dimesylate in a counter-balanced order.

Detailed description:

Arms: arm 1: 40 mg of Vyvanse administered q.a.m. or Placebo administered in random, counter-balanced fashion. arm 2: 40 mg of Vyvanse administered q.a.m. or Placebo administered in random, counter-balanced fashion.
Interventions: intervention 1: Lisdexamfetamine Dimesylate 40 MG intervention 2: Placebo
Intervention descriptions: intervention 1: Lisdexamfetamine Dimesylate 40 MG administered orally intervention 2: Placebo capsule administered orally

Protocol documents:
Prot_SAP_000.pdf: 
 
Efficacy of Lisdexamfetamine Dimesylate for Promoting Occupational Success in Young Adults With 
ADHD 
 
NCT03446885 
 
Document Date: September 23, 2020 
 
 


Participants were recruited through flyers at local venues (e.g., coffee shops, restaurants), 
social media advertisements, flyer mailing to psychiatrists, pediatricians, and other 
professionals, and direct mailings to participants who had previously expressed interest on 
being included on a mailing list. All participants had to have an estimated full-scale IQ above 70, 
a valid driving license or permit, no history of severe motion sickness, and no current 
psychoactive medication for another psychological disorder. Participants taking medication for 
ADHD had to agree to participate in the laboratory activities on a day that they did not take 
their current prescribed medication. 
To determine eligibility for the study, participants completed (1) a self-report of ADHD 
symptoms using the Disruptive Behavior Disorders rating scale ADHD Items (Molina, Smith, & 
Pelham, 2001; Pelham et al., 1992); (2) the Impairment Rating Scale modified to include 
functional domains appropriate for a young adult (Fabiano et al., 2006; Sibley et al., 2012a) 
based on the last six months; (3) a semi-structured Disruptive Behavior Disorders interview to 
obtain contextual information on symptoms and impairment over the last six months (Hartung 
McCarthy, Milich, & Martin, 2005); and (4) the Wechsler Abbreviated Scale of Intelligence 
(Wechsler, 2011). A collateral rater (i.e., the participant’s parent in 90% of cases or another 
adult who knew the participant’s developmental history) also reported on the participant’s 
ADHD symptom ratings for the past six months and retrospectively using the Disruptive 
Behavior Disorder Rating Scale ADHD items. Collaterals also completed an Impairment Rating 
Scale based on the last six months. Collateral raters were compensated with a $25 gift card for 
completing the forms. Participants were diagnosed with ADHD if they had (1) five or more 
inattentive and/or hyperactive impulsive behaviors endorsed as present in the last six months 


across the self-report, collateral, and interview sources, (2) evidence of historical ADHD 
symptoms (e.g., the collateral rater endorsed a clinically significant amount of childhood 
symptoms), and (3) present psychosocial impairment significant enough to warrant treatment 
as rated by self and/or collateral (Sibley et al., 2012a; Sibley et al., 2012b). 
Participants received a $25 gift card for completing a physical visit, and $75 for 
attending each laboratory visit. Thus, they had an opportunity to earn up to $175 in gift cards 
for completing the entire study. Of the 22 participants that met the study’s eligibility criteria, 
36% met criteria for the primarily inattentive presentation, 55% met criteria for combined 
presentation, 5% met criteria for hyperactive/impulsive presentation, and 5% met criteria for 
ADHD, unspecified (American Psychiatric Association, 2013). Table 1 lists demographic 
information on the participants.  
The majority of participants were also currently employed (75%). Of the employed 
participants, two were in their first job, with the remainder having other, prior jobs in the last 
five years (Range = 1-5; Median = 4). For these currently employed participants, two were in 
salaried, full-time professional positions ($34,500 and $54,000 salaries), three worked full-time 
in hourly positions (i.e., 40 hours a week), and the remainder worked 23 or fewer hours per 
week. Removing the salaried positions, the average hourly pay rate for the currently employed 
participants was $11.47 (SD = $1.08). Considering the entire employment history of the 
participants, 95% (N = 19) had been employed at some time.  For these participants, eight had 
worked in a food service or delivery position (e.g., dishwasher, barista, fast food, 
waiter/waitress, cook). Other occupations included lifeguarding, retail (e.g., cashier), 


production (e.g., in a factory that made boxes), and clerical office work (e.g., reception, 
scanning papers).  
Procedures  
 
The study was approved by the Institutional Review Board and registered at 
clinicaltrials.gov (NCT03446885). Upon enrollment into the study, participants were scheduled 
for two, three-hour visits to the Laboratory Assessment of Behavior in Occupational Roles 
(LABOR; Fabiano et al., 2018). The study utilized a within-subjects crossover design with two 
conditions: (1) single dose of placebo (micronized methylcellulose powder) and (2) a single dose 
of 40 mg lisdexamfetamine dimesylate (Vyvanse® Shire Pharmaceuticals). Lisdexamfetamine is 
a Schedule II central nervous stimulant prodrug that is converted to the active component 
dextroamphetamine. It was approved by the FDA as a treatment for ADHD in 2007 
(www.drugs.com/history/vyvanse.html).  
At the start of each visit to LABOR, participants first confirmed that they did not take 
any medication for ADHD that day. Order of study condition was randomized and counter-
balanced by the unblinded study pharmacist. Medication and placebo were placed in identical 
opaque blue capsules by the unblinded study pharmacist.  Both the participant and the study 
staff were blinded to the medication condition and order of medication or placebo dose 
administration. Participants were then administered either placebo or 40 mg lisdexamfetamine 
dimeslyate prior to engaging in the simulated workplace environment. Several studies of both 
children and adults have shown that the mean plasma concentration of dextroamphetamine 
(i.e., the active component) reaches above the limit of quantitation within 30 minutes of the 
administration of lisdexamfetamine dimesylate, with many participants experiencing 


therapeutic effects within the 1st hour of drug administration (Boellner, Stark, Krishnan, & 
Zhang, 2010; Elbe, Macbride, & Reddy, 2010; Krishnan, Pennick, & Stark, 2008). Thus, a 
medication wait period of 30-60 minutes was implemented to promote ecological validity (e.g., 
administration of medication immediately prior to beginning work shift) and to ensure that 
participants were experiencing therapeutic levels of the drug by the time they started the 
workplace paradigm.   
After completing the medication wait period, during which they completed several 
psychosocial surveys, participants were introduced to the LABOR analogue workplace. The 
LABOR analogue workplace setting included the completion of an online job application, which 
consisted of a series of questions typical of job applications for fast food restaurants, and 
participation in a video-recorded job interview, in which the interviewer asked a set of 13 open-
ended questions. Interviewers were trained to ask the question and wait for the participant’s 
response prior to going to the next question. At the completion of the final question, the 
interviewer congratulated the participant on completing the interview and “offered the job” by 
providing the participant an apron to put on before starting work. 
Participants subsequently completed an orientation session where the job tasks, 
delivery procedures, and driving simulator were introduced and practiced (See Figure 2).  The 
LABOR assessment included 40-minutes of job tasks commonly associated with working in a 
pizza place (i.e., creating 100 napkin bundles enclosing a fork, knife, and spoon, preparing 100 
to-go bags with napkin bundles and condiments, and folding 25 pizza boxes) and a 5-min menu 
search task, in which participants were given a pizzeria menu and asked to find and calculate 
prices for a series of guest checks. This was followed by approximately 30-minutes of delivery 


preparation and simulated delivery on a high-fidelity driving simulator. Following the 
completion of the final delivery and a return to the pizza restaurant, the participant completed 
some final ratings and was debriefed (see Figure 2 and Fabiano et al., 2018 for more details 
regarding the LABOR analogue workplace.) The LABOR analogue workplace setting and 
procedures were identical for both visits.  
Measures 
Job Application and Interview 
Application rating. Five independent coders reviewed each application and completed a 
rating form asking  them to make an overall evaluation regarding whether the person was an 
acceptable job candidate for an interview using a scale of 1 (“definitely not”) to 5 (“definitely”). 
The intra-class correlation for the ratings of overall acceptability of the job candidate was .91. 
The average score across raters was used as a dependent measure. 
Interview rating. Five coders who were unaware of the study participant identities or 
medication/placebo status viewed the job interview videotape and completed a form. Raters 
provided a rating of their overall impression of the interview behavior ranging from a score of 
one (Poor) to four (Outstanding). The intra-class correlation for the ratings of overall impression 
of the interview behavior was .90. The average score of the five coders for each participant was 
utilized as a dependent measure.  
In addition to these ratings of the interview performance, the rater also completed the 
five-item inattentive/overactive (I/O) factor of the Iowa Conners rating scale to assess the 
participants’ level of ADHD symptoms during the interview (Atkins, Pelham, & Licht, 1989; 
Milich, Loney, & Landau, 1982; Pelham, Milich, Murphy, & Murphy, 1989). The five items were 


rated on a scale of Not at all (0) to Very much (3) and the sum of these items represents the 
score. Inter-rater reliability for the job interview codes were acceptable, with intra-class 
correlations ranging from .75 to .89.  
Job Performance 
Item completion. Each participant was instructed on how to complete item preparation, 
similar to the expectations within the front end of a restaurant. All participants were instructed 
to complete the napkin rings first, then the take-out bags, and then the pizza boxes, in that 
order. Participants were instructed that they had to complete one entire task prior to 
proceeding to the next task. The dependent measures from this aspect of the study were the 
number of items completed correctly. The total number of items assigned was 223. Similar to 
studies of child productivity, participants were purposely given many more items to complete 
than could be reasonably done in 40 minutes to prevent a ceiling effect (e.g., Fabiano et al., 
2007; Pelham, et al., 1993).  
Delivery Performance. Participants completed two simulated deliveries on the high 
fidelity driving simulator.  In order to complete these tasks, participants had to put together the 
order from the laboratory “kitchen”, they had to package the order appropriately, and then 
drive to the address in the simulator, exit the vehicle, deliver the correct items, and make 
change correctly from the customer. The experimenter also completed a checklist of each item 
that was delivered, and indicated whether this was a correct item according to the order. 
Further, for each delivery, the experimenter noted whether the participant made correct 
change from the payment. The percentage of delivery tasks completed correctly was used as 
the dependent measure.  


Delivery Rating. Following the deliveries, the experimenter made a rating of the overall 
neatness and organization of the presented items delivered.  
Driving Rating. During the deliveries, the experimenter watched each participant on the 
driving simulator and completed a survey of the participant’s driving.  Number of roadway rule 
violations, imprudent decisions, and collisions were noted. Following the two delivery trips, the 
experimenter provided an overall rating of the driving performance (i.e., 1 = “Poor“ to 10 = 
“Excellent”).  
Integrity of LABOR Environment and Experimental Manipulation 
 
To ensure an identical workplace environment at both visits and across all participants, 
the laboratory set-up was operationalized in a written protocol. In addition to a manual that 
specified the placement of all workplace materials, the environment used in the driving 
simulation was programmed to be consistent at both visits and across all the participants. A 
script was used for the job application instructions, job interview questions, and all interactions 
used to orient and prompt the participants during the experiment.  
 
Independent observations of the laboratory sessions indicated that the laboratory was 
correctly set-up for the LABOR evaluation 93% of the time (e.g., on three instances the 
delivery/job task items were incorrectly placed). On 98% of occasions, all components of the 
visit were completed. That is, one participant in the placebo condition did not complete the 
workplace task or the delivery task due to illness not related to the experiment. Furthermore, a 
second participant elected to not complete the second visit. The data from these two 
participants were not included in the final analysis.  


 
Following the completion of the laboratory tasks, participants were asked to rate their 
experiences within the environment. There were no significant differences between groups on 
ratings of workplace realism (1 = Not at all realistic to 10 Very realistic); mean scores were 6.95 
(SD = 1.70) and 7.10 (SD = 1.45) for placebo and medication conditions, respectively. When 
asked about driving simulator realism, the mean scores were 7.10 (SD = 1.62) and 6.65 (SD = 
1.84) for placebo and medication conditions, respectively. Participants were also asked to rate 
their effort during the experience (1 = No effort at all to 10 All my effort), and the mean scores 
were 7.40 (SD = 2.06) and 8.15 (SD = 1.60) for placebo and medication conditions, respectively. 
Finally, participants were asked “To what degree was your behavior the same as it would be in 
a real workplace setting?” and ratings ranged from one (Not at all the same) to 10 (Exactly the 
same), and mean scores were 7.40 (SD = 1.93) and 7.75 (SD = 1.55) for placebo and medication 
conditions, respectively. These self-ratings from the participants indicate that, in general, the 
environment reasonably approximated a workplace environment, and participants’ own effort 
and behavior approximated an authentic workplace.  
Statistical Analysis 
 
Data were analyzed using a repeated measures, multivariate analysis of variance 
(MANOVA). Analyses were conducted for the pre-employment application and interview 
variables (application rating, interview rating, and I/O score during the interview), for the 
productivity variable (items completed), and for the delivery variable (delivery performance, 
delivery rating, and driving rating), separately. Medication status (medication, placebo) was 
entered as a within-subjects variable, and for all analyses order (placebo first vs. medication 
first) was entered as a covariate. Following the overall multivariate analysis, univariate tests 


were conducted. Estimates of effect size were calculated by calculating partial eta2. The 
primary outcomes listed in clinicaltrials.gov (NCT03446885) were application ratings, ratings of 
job interview performance, observed workplace productivity, and I/O rating.