Quillivant XR for ADHD in Down Syndrome

(TEAM-DS Trial)

Recruiting at 2 trial locations

Overseen By Emily K Hoffman, MEd

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: ADHD stimulants, MAOIs

Disqualifiers: Psychoses, Bipolar, Organic brain injury, Heart conditions, Severe OSA, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking ADHD stimulant or non-stimulant medication, you will need to stop for at least 3 days before starting the study. If you are on a stable dose of non-ADHD, non-MAO psychotropic medication, you can continue as long as there have been no dose changes for at least 4 weeks before the study.

What data supports the effectiveness of the drug Quillivant XR for ADHD in Down Syndrome?

Quillivant XR, a long-acting form of methylphenidate, has been shown to effectively reduce symptoms of ADHD by increasing certain brain chemicals. It is particularly useful for those who have difficulty swallowing pills, offering similar benefits to other ADHD medications. ^{1 2 3 4 5}

Is Quillivant XR safe for use in humans?

Quillivant XR, a form of methylphenidate, has been studied for safety in treating ADHD. Common side effects include decreased appetite, weight loss, trouble sleeping, high blood pressure, and mood changes, which are consistent with known effects of methylphenidate. ^{2 3 6 7 8}

How is Quillivant XR different from other ADHD drugs?

Quillivant XR is unique because it is the first long-acting liquid form of methylphenidate, making it easier for people who have trouble swallowing pills to take their medication. It provides a consistent release of the drug throughout the day, reducing the need for multiple doses and potentially improving adherence to treatment. ^{1 2 3 4 9}

What is the purpose of this trial?

Children with Down syndrome (DS) have a 3-5 time greater prevalence of Attention Deficit Hyperactivity Disorder (ADHD) than typically developing (TD) children. Despite this higher risk of ADHD, rates of stimulant medication treatment are disproportionately low in children with DS+ADHD, even though stimulants are the most efficacious ADHD treatment and are recommended by consensus guidelines for use in children with intellectual disability and ADHD. The investigators propose the first randomized clinical trial (RCT) of stimulant medication in children with DS+ADHD. This RCT may provide evidence regarding the short- and long-term safety and efficacy of stimulant use in children with DS+ADHD, both with and without CHD. All children enrolled in the study will complete a comprehensive assessment battery evaluating ADHD diagnostic criteria, as well as behavioral, cognitive, academic, and functional impairments.

Research Team

Anna Esbensen, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Tanya Froehlich, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Kathleen Angkustsiri, MD

Principal Investigator

University of California Davis MIND Institute

Benjamin Handen, MD

Principal Investigator

University of Pittsburgh Medical Center

Sabrina Sargado, MD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for children aged 6 to 17 with Down syndrome and ADHD who can take oral medication, speak English, and meet specific ADHD criteria. They must be willing to follow the study plan and not have brain injuries, severe sleep apnea, certain heart conditions, or be on current ADHD meds they can't stop.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

You show signs of ADHD, such as being very active, having trouble paying attention, or showing a combination of these behaviors during the KSADS evaluation.

I can take medicine by mouth.

Exclusion Criteria

You are allergic to methylphenidate or any of the ingredients in the medication, like banana.

I am taking ADHD medication and cannot stop it for 3 days before the study.

I am currently adjusting doses for my non-ADHD mental health medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline intelligence, diagnostic, behavioral, cognitive, health, and functioning assessments

1 week

1 visit (in-person)

Phase 1: Titration

Participants begin the lowest dose of MPH and titrate incrementally upward; biweekly diagnostic and health assessments

6 weeks

6 visits (in-person)

Phase 2: Randomization

Participants randomized to receive optimal dose of MPH or placebo; repeat of baseline measures

2 weeks

1 visit (in-person)

Phase 3: Crossover

Participants crossover to the study intervention not previously assigned; repeat of assessments

2 weeks

1 visit (in-person)

Phase 4: Open-label Maintenance

Participants undergo an open label trial with their optimal MPH dose for a four-month maintenance period; monthly assessments

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Placebos
• Quillivant XR

Trial Overview The trial tests Quillivant XR (a stimulant medication) against a placebo in children with Down syndrome who also have ADHD. It's designed to see if this medicine is safe and works well over both short and long terms compared to no active treatment.

Participant Groups

Group I: Quillivant XR Active Control 1 Intervention

Once-daily, long-lasting MPH solution with the following dosing schedules: 7.5mg/15mg/22.5mg/30mg for children 20-25kg 10mg/20mg/30mg/40mg for children 26-30kg 10mg/22mg/34mg/46mg for children \> 30 mg

Group II: Placebo Placebo Group 1 Intervention

Liquid-based suspension to match the color and banana-flavor of Quillivant XR.

Quillivant XR is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Quillivant XR for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in European Union as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in Canada as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Boston Children's Hospital, Boston, MA, USA

Collaborator

Trials

4

Recruited

2,600+

University of California, Davis

Collaborator

Trials

958

Recruited

4,816,000+

Findings from Research

Novel formulations of methylphenidate, including extended-release and chewable options, have been developed to improve adherence in ADHD treatment and show good efficacy and tolerability based on recent trials.

These new formulations may also reduce the potential for abuse and adverse effects, making them a safer alternative for patients who struggle with traditional immediate-release forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability. Cortese, S., D'Acunto, G., Konofal, E., et al.[2018]

Extended-release viloxazine (viloxazine ER) has been shown to significantly improve ADHD symptoms in school-age children and adolescents, with effective doses of 100 mg/d and 200 mg/d for children, and 200 mg/d and 400 mg/d for adolescents, compared to placebo.

As a nonstimulant medication, viloxazine ER offers a faster onset of action (1-2 weeks) than atomoxetine (4 weeks) and is suitable for patients who do not respond to or cannot tolerate stimulant medications, although it carries a boxed warning for suicidal ideation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-Release Viloxazine for the Treatment of Attention-Deficit Hyperactivity Disorder in School-Age Children and Adolescents. Raible, H., D'Souza, MS.[2023]

Methylphenidate immediate-release (MPH-IR) has been effective for over 50 years in treating ADHD by blocking the reuptake of norepinephrine and dopamine, although its exact mechanism is still not fully understood.

The newly developed methylphenidate hydrochloride extended-release oral suspension (MEROS or Quillivant(TM) XR) provides a long-acting alternative for patients who have difficulty swallowing pills, while maintaining similar efficacy and safety profiles as other extended-release formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of methylphenidate hydrochloride extended-release oral suspension for the treatment of ADHD. Childress, A., Sallee, FR.[2022]

Quillivant XR (methylphenidate extended-release oral suspension) significantly reduced ADHD symptoms in children aged 6 to 12 years, as shown in a study with 45 participants using a randomized, double-blind, placebo-controlled design.

The treatment was found to be safe, with no reports of suicidal ideation, and common side effects included decreased appetite, insomnia, and abdominal pain, which are typical for stimulant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Tolerability of a Novel Methylphenidate Extended-Release Oral Suspension (MEROS) in ADHD. Robb, AS., Findling, RL., Childress, AC., et al.[2022]

Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODT) significantly reduced ADHD symptoms in children aged 6-12, with a mean decrease in ADHD-RS-IV scores of -21.4 after dose optimization.

The treatment was generally well-tolerated, with common side effects including decreased appetite and headaches, similar to those seen with other methylphenidate formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Dose Optimization of Methylphenidate Extended-Release Orally Disintegrating Tablet in a Laboratory Classroom Study of Children with Attention-Deficit/Hyperactivity Disorder. Childress, AC., Kollins, SH., Cutler, AJ., et al.[2021]

The study involved 119 preschool children aged 4 to <6 years with ADHD, showing that the methylphenidate hydrochloride extended-release capsule (MPH-MLR) significantly reduced ADHD symptoms, with mean ADHD-RS-IV scores dropping from 40.8 to 19.5 during the open-label phase.

In a double-blind phase, children receiving MPH-MLR had a significantly greater improvement in ADHD symptoms compared to those on placebo, with common side effects including decreased appetite and insomnia, consistent with known effects of methylphenidate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder. Childress, AC., Kollins, SH., Foehl, HC., et al.[2021]

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]

In a phase 3 study involving 90 children aged 6-12 with ADHD, methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) significantly reduced ADHD symptoms compared to placebo, with effects observed from 2 to 8 hours postdose.

The treatment was generally safe and well tolerated, with common side effects including decreased appetite and irritability, but no reports of suicidal ideation, indicating a favorable safety profile similar to other methylphenidate formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder. Wigal, SB., Childress, A., Berry, SA., et al.[2018]

In a study of 62 adults with ADHD, both the immediate release (MAS IR) and extended release (MAS XR) formulations of mixed amphetamine salts showed similar efficacy in reducing ADHD symptoms, as measured by various scales.

While adherence to treatment was comparable between MAS IR and MAS XR when assessed by self-report and pill count, MAS XR demonstrated significantly better adherence according to the Medication Event Monitoring System (MEMS), indicating that the once-daily dosing may support better adherence in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study. Adler, LA., Lynch, LR., Shaw, DM., et al.[2013]

References

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

New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability. [2018]

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

Extended-Release Viloxazine for the Treatment of Attention-Deficit Hyperactivity Disorder in School-Age Children and Adolescents. [2023]

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

The use of methylphenidate hydrochloride extended-release oral suspension for the treatment of ADHD. [2022]

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

Efficacy, Safety, and Tolerability of a Novel Methylphenidate Extended-Release Oral Suspension (MEROS) in ADHD. [2022]

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

Open-Label Dose Optimization of Methylphenidate Extended-Release Orally Disintegrating Tablet in a Laboratory Classroom Study of Children with Attention-Deficit/Hyperactivity Disorder. [2021]

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

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder. [2021]

7. 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]

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

Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study. [2013]