Adderall XR for ADHD

Overseen By Meredith O'Connor, BS

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Gagan Joshi

Must be taking: Non-stimulant ADHD treatment

Must not be taking: MAOIs, Stimulants

Disqualifiers: Intellectual disability, Cardiac disease, Seizures, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

196 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stop taking stimulant medications, but those on a stable dose of non-stimulant ADHD medications can continue. If you are on a psychotropic medication, your dose must be stable for at least 4 weeks before starting the study.

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

Research shows that Adderall XR, a long-acting form of Adderall, is effective in treating ADHD in children and adults, with a single dose lasting up to 12 hours. It has been found to be more effective than a non-stimulant drug called atomoxetine and has shown positive effects on quality of life in children with ADHD. ^{1 2 3 4 5}

Is Adderall XR safe for humans?

Adderall XR has been shown to be generally safe for treating ADHD in children, adolescents, and adults, but it was withdrawn from the Canadian market in 2005 due to concerns about heart-related issues and strokes in a small number of people. ^{1 3 4 6 7}

How is the drug Adderall XR unique for treating ADHD?

Adderall XR is unique because it is an extended-release formulation that provides a single daily dose lasting up to 12 hours, which can improve convenience and adherence compared to multiple daily doses. It has shown superior efficacy to some non-stimulant treatments and has a distinct two-stage delivery system that offers unique advantages. ^{1 3 4 5 8}

What is the purpose of this trial?

The investigators are conducting a 10-week brain imaging and medication study. They are doing the research to study the response of Attention-Deficit/ Hyperactivity Disorder (ADHD) in youth with Autism Spectrum Disorder (ASD) on extended-release formulation of mixed amphetamine salts (MAS) (also know as Adderall XR). The investigators also want to find out if taking MAS has any effect on the brains of children and adolescents with ADHD and ASD. This study will help researchers better understand how the use of MAS to treat ADHD effects children and adolescents with ASD. The investigators will compare MAS to a placebo. The placebo will look exactly like the MAS capsules but will contain no MAS. During this study, participants may get a placebo instead of MAS. Placebos are used in research studies to see if the study results are due to the study drug or due to other reasons. Participants with ASD and ADHD will complete 4-weeks of treatment with the study medication or placebo. They will complete bi-weekly study visits virtually via a telemedicine platform with the study doctor and complete questionnaires. On alternating weeks, they will meet with a Massachusetts General Hospital (MGH) study team member to discuss medication adherence and potential side effects. Participants will have the option to attend all study visits in-person if participants prefer. They will also complete baseline and endpoint Magnetic Resonance (MR) scan visits at Massachusetts Institute of Technology (MIT). During the MR Scan visits, they will complete a series of tasks to measure inattention, impulsivity, reward sensitivity, decision-making, and working memory. Participants without ADHD or ASD will complete eligibility screening with MGH. If eligible, they will be invited to baseline and endpoint MR scan visits at MIT. During the MR Scan visits, they will complete a series of tasks to measure inattention, impulsivity, reward sensitivity, decision-making, and working memory.

Research Team

Gagan Joshi, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for children and adolescents with both Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). They will be tested to see how a medication called Adderall XR, which is used for ADHD, affects their brain function. Participants must be able to attend study visits virtually or in person and undergo MRI scans.

Inclusion Criteria

Participants with Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder

Must meet DSM-5-TR diagnoses of ADHD and ASD as established by clinical diagnostic interview

Must have at least moderate current ADHD symptoms severity (Clinician-rated ADHD-RS score ≥28 and ADHD-CGI-S of ≥4)

Exclusion Criteria

Participant unable to swallow pills (ASD participants only)

History of substance use (except nicotine, recreational use of THC, or caffeine) within the past 3 months

Participants with poor command of the English language and/or require an interpreter

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive either mixed amphetamine salts (MAS) or placebo for 4 weeks, with bi-weekly virtual visits and MR scans at baseline and endpoint

4 weeks

2 visits (in-person for MR scans), 2 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adderall XR

Trial Overview The TEAM Study tests the effectiveness of Adderall XR compared to a placebo over 10 weeks. It involves virtual bi-weekly check-ins, questionnaires about behavior changes, adherence discussions, and two MRI scans at MIT to assess brain activity related to attention and decision-making.

Participant Groups

Group I: Mixed Amphetamine Salts (MAS) (also known as Adderall XR) Experimental Treatment 1 Intervention

Participants in the MAS arm will receive MAS in capsule form daily for 4 weeks . Participants will undergo neuroimaging before and after the 4-week treatment phase.

Group II: Control Group Active Control 1 Intervention

Typically-developing controls will undergo neuroimaging twice (4 weeks apart) and will receive no intervention during the 4-week window.

Group III: Placebo Placebo Group 1 Intervention

Participants in the placebo arm will receive placebo (no active ingredients) in capsule for daily for 4 weeks. Participants will undergo neuroimaging before and after the 4-week treatment phase.

Who Is Running the Clinical Trial?

Gagan Joshi

Lead Sponsor

Trials

1

Recruited

200+

Massachusetts Institute of Technology (MIT)

Collaborator

Trials

2

Recruited

200+

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) 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]

A review of 43 studies involving around 7000 children found that common adverse drug reactions (ADRs) from ADHD medications included decreased appetite, gastrointestinal pain, and headaches, primarily reported by children or their parents.

Most studies reported low rates of serious ADRs, but many children dropped out due to serious reactions, suggesting that the actual incidence of serious ADRs may be higher, highlighting the need for long-term safety studies on ADHD medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The occurrence of adverse drug reactions reported for attention deficit hyperactivity disorder (ADHD) medications in the pediatric population: a qualitative review of empirical studies. Aagaard, L., Hansen, EH.[2021]

References

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

The impact of the withdrawal of Adderall XR (long-acting mixed amphetamine salts) from the Canadian market on paediatric patients and their families. [2021]

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

Analog classroom assessment of a once-daily mixed amphetamine formulation, SLI381 (Adderall XR), in children with ADHD. [2006]

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

Long-term tolerability and effectiveness of once-daily mixed amphetamine salts (Adderall XR) in children with ADHD. [2006]

6. New Zealand pubmed.ncbi.nlm.nih.gov

The occurrence of adverse drug reactions reported for attention deficit hyperactivity disorder (ADHD) medications in the pediatric population: a qualitative review of empirical studies. [2021]

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

Characteristics of online pharmacies selling Adderall. [2021]

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

Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall. [2007]