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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Quillivant XR (Methylphenidate Hydrochloride Extended-Release Oral Suspension) to determine its effectiveness for children with both Down syndrome (DS) and Attention Deficit Hyperactivity Disorder (ADHD). Children with DS are more likely to have ADHD but often do not receive stimulant treatments like others. The study aims to assess the medication's safety and effectiveness for this group. It will evaluate the treatment's impact on attention and behavior over time. Children diagnosed with ADHD and DS might be suitable candidates, especially if they are not currently on ADHD medication. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand its benefits for a broader patient population.

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 is the safety track record for Quillivant XR?

Previous studies have shown that Quillivant XR, a liquid form of methylphenidate, safely treats ADHD in children as young as six. The treatment is generally well-tolerated, with most side effects being mild. Common side effects include trouble sleeping, decreased appetite, and stomach pain, similar to those of other ADHD medications.

The FDA has already approved Quillivant XR for treating ADHD, indicating a strong safety record for use in children. As with any medication, monitoring for signs of misuse or dependence is important. Existing research shows that Quillivant XR is generally safe for children with ADHD. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for ADHD in children with Down Syndrome, such as behavioral therapy and stimulant medications like methylphenidate and amphetamine, Quillivant XR offers a unique once-daily, long-lasting liquid formulation. This makes it easier for children who might have difficulty swallowing pills. Additionally, Quillivant XR provides flexible dosing options tailored to the child's weight, ensuring more precise management of symptoms. Researchers are excited about Quillivant XR because it combines the effectiveness of a well-known active ingredient, methylphenidate, with convenient dosing and administration, potentially improving adherence and outcomes for children with Down Syndrome and ADHD.

What evidence suggests that Quillivant XR might be an effective treatment for ADHD in children with Down syndrome?

Research shows that Quillivant XR, a long-lasting liquid form of methylphenidate, helps treat ADHD by increasing levels of norepinephrine and dopamine, two brain chemicals important for attention and focus. Previous studies found that Quillivant XR significantly reduces ADHD symptoms in children. In this trial, some participants will receive Quillivant XR, while others will receive a placebo. Although the current study focuses on children with both Down syndrome and ADHD, Quillivant XR has already proven effective for children with ADHD in general. Due to its proven effectiveness, Quillivant XR is considered a promising option for managing ADHD symptoms in various groups. ^{6 7 8 9 10}

Who Is on the Research Team?

Sabrina Sargado, MD

Principal Investigator

Boston Children's Hospital

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02255565

Dose Response Effects of Quillivant XR in Children With ... The purpose of this study is to determine whether Quillivant XR is effective in the treatment of ADHD in children with Autism Spectrum Disorder (ASD). Detailed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5774317/

Methylphenidate extended-release oral suspension for the ... MEROS is a once daily, long-acting liquid preparation that has demonstrated favorable safety and efficacy in patients with ADHD.

3. withpower.com withpower.com/trial/phase-2-down-syndrome-9-2020-7759a

Quillivant XR for ADHD in Down Syndrome (TEAM-DS Trial) Methylphenidate immediate-release (MPH-IR) has been effective for over 50 years in treating ADHD by blocking the reuptake of norepinephrine and dopamine, ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/202100s012lbl.pdf

QUILLIVANT XR® (methylphenidate hydrochloride) for extended QUILLIVANT XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The efficacy of QUILLIVANT XR was established in a 2-week ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00904670

Study Details | NCT00904670 | Quillivant Oral Suspension ... The objective of this study was to establish that an optimal dose of Quillivant XR oral suspension would result in a significant reduction in signs and ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/202100lbl.pdf

QUILLIVANT XR (methylphenidate hydrochloride) Label QUILLIVANT XR is a liquid medicine that you take by mouth. It is used for the treatment of Attention-Deficit. Hyperactivity Disorder (ADHD). QUILLIVANT XR may ...

7. fda.gov fda.gov/media/112433/download

Quillivant XR® (methylphenidate HCl) for extended- ... Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Warnings and Precautions (5.1) ...

8. quillivantxr.com quillivantxr.com/

Quillivant XR® (methylphenidate HCl) ADHD Medication | Tris ... Quillivant XR®, a once-daily liquid methylphenidate ADHD treatment for ages 6 and up. See Boxed Warning regarding Abuse, Misuse, and Addiction.

9. mayoclinic.org mayoclinic.org/drugs-supplements/methylphenidate-oral-route/description/drg-20068297

Methylphenidate (oral route) - Side effects & dosage Methylphenidate works in the treatment of ADHD by increasing attention and decreasing restlessness in children and adults who are overactive, ...

10. pdf.hres.ca pdf.hres.ca/dpd_pm/00072613.PDF

product monograph Quillivant ER Oral Suspension is used to treat Attention Deficit Hyperactivity Disorder (ADHD) in children 6-12 years of age. Quillivant ER ...