Stimulant Medication for ADHD

Overseen By Cynthia M Hartung, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wyoming

Must not be taking: SSRIs, SNRIs, Sedatives, others

Disqualifiers: Seizure disorder, Bipolar, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

If you are currently taking a prescription stimulant for ADHD, you will need to stop taking it the day before and the day of any study visits. Additionally, you cannot participate if you are using other psychotropic drugs or certain medications that could interact with Adderall.

What data supports the effectiveness of the drug Adderall XR for treating ADHD?

Research shows that Adderall XR, a long-acting form of Adderall, is effective in treating ADHD in children and adults. It provides symptom control throughout the day with a single morning dose and has been shown to improve behavior and cognitive performance. ^{1 2 3 4 5}

Is stimulant medication for ADHD, like Adderall XR, generally safe for humans?

Adderall XR, a long-acting stimulant for ADHD, has been shown to be safe and effective in both children and adults. Common side effects include nausea and decreased appetite, but the overall safety profile is similar to other stimulant medications. ^{1 2 4 5 6}

What makes Adderall IR 10mg unique for treating ADHD?

Adderall IR 10mg is unique because it contains mixed amphetamine salts that provide a quick onset of action, making it effective for immediate symptom relief in ADHD, unlike extended-release versions that are designed for all-day coverage. ^{1 2 3 7 8}

Research Team

Cynthia M Hartung, Ph.D.

Principal Investigator

University of Wyoming

Eligibility Criteria

This trial is for college students aged 18-29 with ADHD who have been previously diagnosed and report significant inattention symptoms. They must be native English speakers, not pregnant, non-smokers, and not using conflicting medications or substances. Healthy peers without ADHD are also included as controls if they match an ADHD participant's age and sex.

Inclusion Criteria

Be between the ages of 18-29

You have been diagnosed with ADHD and experience five or more symptoms of inattention according to the DSM-5 Symptom Checklist.

If you are a healthy participant, you must not have been diagnosed with ADHD and should have very few symptoms of inattention and hyperactivity/impulsivity.

Exclusion Criteria

Participants will be excluded if they are pregnant (determined by a urine pregnancy test), are attempting to become pregnant, or are currently breastfeeding

Not meeting any of the above stated inclusion criteria

Any contraindications for physical exercise placing the participant at moderate or high-risk

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Participants attend a baseline appointment to confirm eligibility and complete baseline measures

1 week

1 visit (in-person)

Experimental Appointments

Participants attend two experimental appointments where they receive either a placebo or stimulant and complete cognitive tests

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Remote follow-up via questionnaires

Treatment Details

Interventions

• Adderall IR 10mg
• Placebo

Trial Overview The study tests the immediate effects of Adderall IR (a stimulant medication) on executive functioning in college students with ADHD compared to a placebo. The goal is to see if Adderall improves attention and working memory better than no treatment at all.

Participant Groups

Group I: Stimulant Medication Experimental Treatment 2 Interventions

Participants will be administered a stimulant medication (Adderall IR 10mg). The ordering of experimental vs. placebo appointments will be counterbalanced. Participants will complete computer-based tests of sustained attention and working memory during all appointments.

Adderall IR 10mg is already approved in United States, Canada for the following indications:

Approved in United States as Adderall for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in Canada as Adderall for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Who Is Running the Clinical Trial?

University of Wyoming

Lead Sponsor

Trials

20

Recruited

1,600+

Findings from Research

Adderall XR is a long-acting psychostimulant approved for treating ADHD in both children and adults, with a 12-hour duration of action and demonstrated superior efficacy compared to the nonstimulant atomoxetine.

The largest effectiveness trial for ADHD therapies confirmed that Adderall XR significantly improves quality of life in children and shows proven safety and efficacy in adults, with potential benefits for treating comorbid conditions like oppositional defiant disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adderall XR: long acting stimulant for single daily dosing. Sallee, FR., Smirnoff, AV.[2019]

SLI381 (Adderall-XR) has been shown to be a safe and effective treatment for ADHD in over 500 patients, with therapeutic effects lasting up to 12 hours, particularly at higher doses.

The side effects of SLI381 are similar to those of the existing Adderall preparation, with no significant increase in incidence except for anorexia, making it a reliable once-daily dosing option for ADHD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SLI381: a long-acting psychostimulant preparation for the treatment of attention-deficit hyperactivity disorder. Grcevich, S.[2019]

SLI381 (Adderall XR) demonstrated significant, dose-related improvements in ADHD symptoms in children aged 6 to 12 years, with consistent efficacy observed throughout the day, as measured by both teachers and parents.

The study, involving 584 children in a randomized, double-blind trial, showed that SLI381 was well-tolerated with a low incidence of adverse events, indicating it is a safe and effective once-daily treatment for ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder. Biederman, J., Lopez, FA., Boellner, SW., et al.[2019]

The study demonstrated that AMP XR-OS, a new extended-release amphetamine oral suspension, is bioequivalent to Adderall XR, as shown by pharmacokinetic parameters in 42 healthy adult volunteers.

Safety monitoring revealed that the most common side effects were nausea and decreased appetite, indicating that AMP XR-OS has a similar safety profile to Adderall XR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults. Sikes, C., Stark, JG., McMahen, R., et al.[2022]

A study involving 32 healthy adults found that coingestion of varying concentrations of alcohol (4%-40%) did not significantly affect the absorption or pharmacokinetics of the ADHD medication Adzenys™ XR-ODT (amphetamine).

The safety profile was consistent with known effects of amphetamine and alcohol, indicating that the combination does not lead to dose dumping or altered drug effectiveness, which is important for clinicians treating ADHD patients who may also consume alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase I Study to Assess the Effect of Alcohol on the Pharmacokinetics of an Extended-release Orally Disintegrating Tablet Formulation of Amphetamine in Healthy Adults. Newcorn, JH., Stark, JG., Adcock, S., et al.[2018]

A study using pharmacological MRI in rats showed that D- and L-amphetamine isomers produce different blood-oxygen-level-dependent (BOLD) responses in brain regions associated with cognition and motor control, suggesting they may have distinct effects on brain function.

The L-isomer of amphetamine resulted in greater overall changes in brain activity compared to the D-isomer, particularly in areas like the somatosensory and motor cortices, which could influence treatment strategies for ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effects of the D- and L- isomers of amphetamine on pharmacological MRI BOLD contrast in the rat. Easton, N., Marshall, F., Fone, KC., et al.[2022]

Combination therapy using stimulants and atomoxetine may improve ADHD symptoms in some patients, particularly children and adolescents with the combined subtype, but results vary widely among individuals.

The review highlighted that there were no serious adverse events reported, suggesting that this combination therapy is generally safe, although the evidence is limited and based on a small number of studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability. Treuer, T., Gau, SS., Méndez, L., et al.[2021]

Serdexmethylphenidate (SDX) is a newly approved treatment for ADHD that offers a longer duration of action compared to other stimulant medications, making it a promising option for patients.

Early studies indicate that SDX is safe and has side effects similar to other stimulants, while its prodrug design may help reduce the risk of abuse and allows for flexible administration for those who have difficulty swallowing pills.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating serdexmethylphenidate and dexmethylphenidate capsules as a once-daily treatment option for ADHD. Barnhardt, EA., Narayanan, AR., Coury, DL.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Adderall XR: long acting stimulant for single daily dosing. [2019]

2. England pubmed.ncbi.nlm.nih.gov

SLI381: a long-acting psychostimulant preparation for the treatment of attention-deficit hyperactivity disorder. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A Randomized Phase I Study to Assess the Effect of Alcohol on the Pharmacokinetics of an Extended-release Orally Disintegrating Tablet Formulation of Amphetamine in Healthy Adults. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Differential effects of the D- and L- isomers of amphetamine on pharmacological MRI BOLD contrast in the rat. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Evaluating serdexmethylphenidate and dexmethylphenidate capsules as a once-daily treatment option for ADHD. [2023]