Clinical trial NCT03935646: Acute Effects of Stimulant Medication in College Students With ADHD
Official title: Acute Effects of Prescription Stimulant Medication on Cognition and Mood in College Students With and Without ADHD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Attention Deficit Hyperactivity Disorder
Stimulant Use
Working Memory
Change in Sustained Attention
Mood
Keywords: Attention Deficit Hyperactivity Disorder
Stimulant Use
Working Memory
Change in Sustained Attention
Mood
Lead sponsor: University of Wyoming
Sponsor class: OTHER
First posted: 2019-05-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a mixed (within-subjects and between-subjects) design. ADHD and comparison participants will complete outcome measures at baseline and at two counter-balanced experimental sessions (placebo, Adderall).
Primary purpose: TREATMENT

Brief summary: The investigators will examine the acute effects of stimulant medication on executive functioning. The rationale for the proposed study is to examine the efficacy of stimulants for college students with ADHD and help prevent stimulant misuse among college students without ADHD. The working hypothesis is that stimulants, compared to baseline and placebo conditions, will improve executive functioning for college students with ADHD but not for college students without ADHD. Improvements on executive functioning measures (e.g., CPT-IP, Spatial Span) will be examined through 2 (ADHD vs. non-ADHD) x 3 (Baseline, Placebo, Stimulant) repeated measures ANOVAs. Follow-up analyses will include paired comparisons.

Expected outcomes are to confirm these hypotheses and demonstrate the need for further study of stimulants. If confirmed, the results will provide pilot data for a larger NIH grant proposal aimed at further examining the acute effects of stimulants (i.e., improved cognitive functioning with stimulants) and comparing them to the acute effects of physical exercise (i.e., improved cognitive functioning immediately after exercise). The investigators expect this outcome to have an important positive impact because it can help support stimulant medication as an effective treatment for college students with ADHD (DuPaul et al., 2012). Additionally, demonstration that stimulants do not improve executive functioning for college students without ADHD can be used to help prevent and discourage stimulant misuse and diversion on college campuses (Hartung et al., 2013).

Detailed description: Participants. The investigators will enroll 40 University of Wyoming (UW) and Laramie County Community College (LCCC) students including 20 with ADHD and 20 without ADHD (20 men, 20 women). Power analyses (G\*Power 3.1; Faul et al., 2007) indicated a sample of at least this size is needed to provide 80% power to detect medium effects. Participants will be recruited through several means including targeted email announcements, flyers, and SONA pre-screener data.

Full exclusion criteria can be found in the "Eligibility" section below. Most notably, participants must stratify as being low risk for stimulant medication use. A health history screening questionnaire and additional health items will be used to screen participants and responses will be reviewed and approved by a medical consultant.

All prospective participants will attend a baseline appointment to confirm eligibility including: (a) being at low risk for stimulant use contraindications and (b) meeting diagnostic threshold for ADHD. After confirming eligibility, participants will also complete baseline measures during the baseline appointment. After enrolling in the study, participants will be scheduled for two experimental appointments. The two experimental appointments will include: (a) Placebo pill and (b) Stimulant (Adderall IR 10mg). The ordering of experimental appointments will be counterbalanced. Experimental appointments will be scheduled in the mornings and on the same day of the week and same time of day. Participants will be asked to abstain from caffeine, alcohol, nicotine, and illicit drugs for 12 hours prior to their appointments. Participants will be administered either placebo or stimulant. After a 90-minute wait, participants will complete executive functioning measures. Physiological measures (e.g., heart rate and blood pressure) will be monitored at specific times throughout the appointment and a medical consultant will be available on call for any emergencies. Participants will also be sent a modified mood (i.e., Depression, Anxiety, and Stress Scale or DASS) and sleep (Pittsburgh Sleep Quality Index or PSQI) questionnaire the morning following all experimental appointments. The only difference between the two appointments is the administration of either placebo or stimulant.

Prior to analyses, all variables will be screened. Violations of statistical assumptions will be addressed through data transformations or nonparametric statistics. Improvements on executive functioning measures (e.g., CPT-IP, Spatial Span) will be examined through 2 (ADHD vs. non-ADHD) x 3 (Baseline, Placebo, Stimulant) repeated measures ANOVAs. When interactions are significant, paired samples t-tests will be used to evaluate group differences. When interaction effects fail to reach statistical significance, independent samples t-tests will be used to evaluate group differences. The magnitude of omnibus effects for repeated measures ANOVAs will be calculated using partial eta-squared (ηp2). Within-group effects (Cohen's d) and corresponding confidence intervals for within-group effect sizes will be standardized using the variability of baseline scores (Howell, 2011). Between-group effects will be calculated using Hedges g (Hedges, 1982).

Eligibility criteria: Inclusion Criteria:

* Be currently enrolled either full time or part time as an undergraduate in a 2-year or 4-year college
* Be between the ages of 18-29
* Be a native English speaker
* ADHD Participants: Must report a prior diagnosis of ADHD and self-report five or more inattention (IA) symptoms on the DSM-5 Symptom Checklist on the pre-screener.
* Healthy Participants: Must disavow ever being diagnosed with ADHD, report 3 or fewer IA symptoms and 3 or fewer hyperactivity/impulsivity (HI) symptoms on the DSM-5 ADHD Symptom Checklist in the pre-screener and are an age and sex match of an ADHD group participant

Exclusion Criteria:

* Not meeting any of the above stated inclusion criteria
* Any contraindications for physical exercise placing the participant at moderate or high-risk. This includes the following:

  1. Participants will be excluded if they report having an acute or uncontrolled disease (cardiovascular, pulmonary, neurological, endocrine, musculoskeletal, immunological).
  2. Participants will be excluded if they are non-ambulatory or rely on walking aids for ambulation.
  3. Participants will be excluded who chronically manage asthma or another respiratory condition or require using an inhaler to complete exercise.
  4. Participants will be excluded if they experience uncontrolled or current problems with syncope (loss of consciousness or fainting) or postural hypotension.
  5. Participants will be excluded if they have ever had a stroke, aneurysm, or transient ischemic attack (TIA).
  6. Participants will be excluded if they have exercise or physical activity restrictions imposed by a health provider.
  7. Participants will be excluded by the medical director due to possible underlying disease/condition or risk.
  8. Participants will be excluded if they are pregnant (determined by a urine pregnancy test), are attempting to become pregnant, or are currently breastfeeding will also be excluded (stated above).
  9. Participants will be excluded for any current use of other psychotropic drugs (e.g., SSRIs, SNRIs, sedatives; stated above).
* Any contraindications for stimulant medication use placing the participant at moderate or high-risk. This includes the following:

  1. Participants will be excluded if they have ever been diagnosed with seizure disorder, high blood pressure, glaucoma, gastrointestinal hypermotility disorder (e.g., IBS), diabetes, hypoglycemia, cardiac problems (e.g., heart disease), or thyroid problems.
  2. Participants will be excluded if they have ever been diagnosed with a bipolar disorder (e.g., Bipolar I or Bipolar II), a psychotic disorder (e.g., schizophrenia), a sleep disorder (e.g., narcolepsy), an eating disorder (e.g., bulimia nervosa), or a severe substance use disorder (e.g., endorsing six or more symptoms of a substance use disorder according to the DSM-5). Participants will also be excluded if they report a past year diagnosis of major depressive disorder, panic disorder, generalized anxiety disorder, or any substance use disorder.
  3. Participants will be excluded if they report any prior treatment for substance use (e.g. rehabilitation for alcohol or other substance use). Additionally, participants will be excluded if they do not agree to abstain from illicit or addictive drugs and marijuana use for the duration of the study beginning with the eligibility assessment.
  4. Participants will be excluded if they experience uncontrolled or current problems with syncope (e.g., loss of consciousness or fainting) or postural hypotension.
  5. Participants will be excluded if they are pregnant (determined by a urine pregnancy test), are attempting to become pregnant, or are currently breastfeeding.
  6. Non-ADHD participants will be excluded if they have ever engaged in non-prescription stimulant use.
  7. ADHD participants who are currently prescribed a prescription stimulant will be asked not to take their medication the day prior to and day of any study visits. They will be excluded if they are not comfortable with abstaining.
  8. Participants will be excluded for any current use of other psychotropic drugs (e.g., SSRIs, SNRIs, sedatives) or non-stimulant ADHD medication (i.e., Strattera).
  9. Participants will be excluded for any current use of any other prescription medication that could interact negatively with Adderall (e.g., neurological and blood-pressure drugs, antihistamines).
  10. They will also be excluded for current use of high levels of caffeine consumption (e.g., daily use more than 600mg/day or about six 8-oz. cups of coffee). Daily use is defined as 5 or more days per week for the last month.
  11. Participants who are using other over-the-counter-substances that could interact negatively with Adderall (e.g., dietary supplements, weight-loss pills, and low-to-moderate levels of caffeine consumption, antihistamines) will be asked to abstain from use for at least 12-hours prior to lab visits. They will be excluded if they are not comfortable with abstaining.
  12. Participants will be excluded if they report current nicotine use (i.e., 5 or more cigarettes per day), daily vaping (i.e., e-cigarettes), smokeless tobacco (i.e., chewing tobacco), nicotine gum, and/or nicotine patches use in the past month.
  13. Participants will be excluded if they experienced a concussion within the past 6 months, have experienced two or more concussions in their lifetime, or have a history of traumatic brain injury.
  14. Participants will be excluded if they have ever had a stroke, aneurysm, or transient ischemic attack (TIA).
  15. Participants will be excluded if they are unwilling to ingest a prescription stimulant medication (Adderall) or placebo in the lab.

Primary outcomes:
measure: Change in Continuous Performance Test - Identical Pairs (CPT-IP) for Adderall vs. Placebo
timeFrame: Completed at baseline and each experimental appointment over a period of three weeks
measure: Change in Spatial Span (SS) for Adderall vs. Placebo
timeFrame: Completed at baseline and each experimental appointment over a period of three weeks
measure: Change in Digit Span for Adderall vs. Placebo
timeFrame: Completed at baseline and each experimental appointment over a period of three weeks
measure: Change in Letter-Number Sequencing for Adderall vs. Placebo
timeFrame: Completed at baseline and each experimental appointment over a period of three weeks
measure: Visual Analogue Scales (VAS) for Adderall vs. Placebo
timeFrame: two weeks
measure: Addiction Research Center Inventory (ARCI) for Adderall vs. Placebo
timeFrame: two weeks
measure: Intentions to Use Questionnaire (IUQ) for Adderall vs. Placebo
timeFrame: two weeks
Secondary outcomes:
measure: Pittsburgh Sleep Quality Index-Modified (PSQI-M)
timeFrame: Completed the day after each experimental appointment over a period of two weeks
measure: Depression, Anxiety, and Stress Scale-Modified (DASS-M)
timeFrame: Completed the day after each experimental appointment over a period of two weeks
measure: DSM-5 ADHD Symptoms Checklist - Modified (DSM 5-M)
timeFrame: Completed the day after each experimental appointment over a period of two weeks
measure: Side Effects Rating Scale - Modified
timeFrame: Completed the day after each experimental appointment over a period of two weeks
measure: Substance Use Day After Questionnaire
timeFrame: Completed the day after each experimental appointment over a period of two weeks
Other outcomes:
Locations:
city: Laramie
country: United States
facility: University of Wyoming
state: Wyoming
Study officials:
affiliation: University of Wyoming
name: Cynthia M Hartung, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hartung CM, Canu WH, Cleveland CS, Lefler EK, Mignogna MJ, Fedele DA, Correia CJ, Leffingwell TR, Clapp JD. Stimulant medication use in college students: comparison of appropriate users, misusers, and nonusers. Psychol Addict Behav. 2013 Sep;27(3):832-40. doi: 10.1037/a0033822.
citation: Dupaul GJ, Weyandt LL, Rossi JS, Vilardo BA, O'Dell SM, Carson KM, Verdi G, Swentosky A. Double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in college students with ADHD. J Atten Disord. 2012 Apr;16(3):202-20. doi: 10.1177/1087054711427299. Epub 2011 Dec 12.