Evaluating Treatment of ADHD in Children with Down Syndrome

NCT04219280 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2019-1016
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Down Syndrome; ADHD

Outcome Measures

Primary Outcomes (2)

• Mean magnitude of change in ADHD Symptoms as measured by parent and teacher report on the Vanderbilt ADHD Parent and Teacher Rating Scales, compared to placebo, during the optimal MPH dosage period. [ Time Frame: Phase 2, Phase 3 ]

  A 49-item parent-report measure used to assess parent and teacher perceptions of youth's school and social functioning. The first 47 items assess symptoms of inattention, hyperactivity, combined inattention and hyperactivity, oppositional-defiant disorder, conduct disorder, and anxiety/depression. These items are scored on a 0-3 scale (0 = Never; 1 = Occasionally; 2 = Often; 3 = Very Often). The next two items measure impairment in performance and are scored on a 1-5 scale (1 = Above Average; 3 = Average; 5 = Problematic). For both sub-scales, lower scores mean better outcomes. Data will be entered into SPSS and used as a diagnostic outcome measure.

  Baseline, Weeks 2-14, Weeks 18, 22, 26, and 30

• Mean magnitude of change in Emotion Regulation as measured by parent and teacher report on the BRIEF2, compared to placebo, during the optimal MPH dosage period. [ Time Frame: Phase 2, Phase 3 ]

  A 63-item parent and teacher rating scale used to assess everyday skills measuring executive functioning, including inhibition, shifting attention, emotional control, initiating tasks, problem solving, working memory, and monitoring activities. All 63-items are scored on a 3-item scale (N = never, S = Sometimes, O = Often). Scoring is performed through a software which generates T-scores for 13 sub-scales, with borderline and clinical ranges identified. Lower scores on this measure indicate better outcomes. Data will be entered into SPSS and used as a behavioral outcome measure.

  Baseline, Week 12, Week 14, and Week 30

Secondary Outcomes (9)

• Mean magnitude change in Externalizing Behaviors as measured by parent and teacher report on the Achenbach Child Behavior Checklist (CBCL/TRF), compared to placebo, during the optimal MPH dosage period. [ Time Frame: Phase 2, Phase 3 ]

  Baseline, Week 12, Week 14, and Week 30

• Mean magnitude of change in Behavior Regulation as measured by parent and teacher report on the BRIEF2, compared to placebo, during the optimal MPH dosage period. [ Time Frame: Phase 2, Phase 3 ]

  Baseline, Week 12, Week 14, and Week 30

• Frequency of clinically significant physician-collected cardiac occurrences on MPH - clinically significant change from baseline in ECG findings during the during the MPH titration trial [Phase 1] and the optimal MPH dosage maintenance period [Phase 4].

  Baseline, Week 8, Week 10, Week 22, and Week 30

• Frequency of clinically significant cardiac occurrences on MPH- clinically significant changes for Heart Rate (HR) during the MPH titration trial [Phase 1] and the MPH dosage maintenance period [Phase 4].

  Baseline, Weeks 2-14, Weeks 18, 22, 26, and 30

• Frequency of clinically significant cardiac occurrences on MPH- clinically significant changes for Blood Pressure (BP) during the MPH titration trial [Phase 1] and the MPH dosage maintenance period [Phase 4].

  Baseline, Weeks 2-14, Weeks 18, 22, 26, and 30

Study Arms (2)

Quillivant XR

ACTIVE COMPARATOR

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

Drug: Quillivant XR

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Quillivant XR DRUG

Long-lasting liquid solution of Quillivant XR.

Quillivant XR

Placebo DRUG

Liquid solution to mimic the color and taste of Quillivant XR.

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, between the ages of 6.00-17.99 years at the time of consent.
• Able to take oral (liquid) medication.
• English is primary language.
• Meets criteria for ADHD (hyperactivity, inattention, or combined) on the KSADS
• Meets criteria for ADHD (hyperactivity, inattention, or combined) on the Vanderbilt (historically or currently, as indicated by a teacher/professional)

You may not qualify if:

• Current use of ADHD stimulant or non-stimulant medication and unwilling to discontinue for \>/= 3 days prior to starting the study.
• Children with psychoses or bipolar disorder based on diagnostic interview with the parent.
• Organic Brain Injury: Children must not have a history of head trauma with loss of consciousness, epilepsy, or any other organic disorder that could possibly affect brain function.
• Specific heart conditions including the following:
• QTc on baseline ECG\>470ms or QTC \> 500 in patients with repaired CHD, as determined by ECG
• Brugada pattern, as determined by ECG
• Baseline heart rate or systolic blood pressure \> 2 SD above mean for age as determined by medical examination.
• nd or 3rd degree AV block, as determined by ECG
• History of aborted sudden cardiac death or unexplained syncope as determined by medical history
• History of a single ventricle as determined by medical history
• Valvular regurgitation or stenosis \> mild, as determined by ECHO
• Moderate or greater ventricular dysfunction, as determined by ECHO
• Pulmonary hypertension, defined as right ventricular pressure \>33% systemic pressure or septal position consistent with \>mild right ventricular hypertension, as determined by ECHO
• Use of a pacemaker as determined by medical history
• Wolff Parkinson White/pre-ventricular excitation, as determined by ECG

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• University of California, Davis: collaborator
• University of Pittsburgh Medical Center: collaborator
• Boston Children's Hospital, Boston, MA, USA: collaborator

Study Sites (4)

University of California Davis MIND Institute

Sacramento, California, 95817, United States

COMPLETED

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15203, United States

RECRUITING

MeSH Terms

Conditions

Down Syndrome; Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Anna Esbensen, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Tanya Froehlich, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Kathleen Angkustsiri, MD

  University of California Davis MIND Institute

  PRINCIPAL INVESTIGATOR

• Benjamin Handen, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

• Sabrina Sargado, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily K Hoffman, MEd

CONTACT

513-803-3641; Emily.Hoffman1@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1 is a Sequential model, Phase 2-3 is a Crossover model, Phase 4 is a Single-Group model.

Study Record Dates

• First Submitted: December 31, 2019
• First Posted: January 7, 2020
• Study Start: October 2, 2020
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Due to the nature of data collection in a blinded randomized clinical trial, data will be made available upon completion of sampling and primary analyses. Data will also be archived in accordance with the scientific journals in which reports from the project are published. Prior to publication, findings from the project will be shared broadly at conferences attended by professionals doing intervention work with the children with intellectual and developmental disabilities, and at scientific meetings attended by researchers focused on intellectual and developmental disabilities.
• Access Criteria: Data will be shared at the completion of the project according to any and all NIH guidelines. Furthermore, data may be shared with colleagues at other sites in the future, but only under conditions specified by the IRBs at the participating universities and research sites, and in a manner consistent with written informed consent provided by the participants.

Locations

US (4)