Summary

Eligibility
for people ages 6-17 (full criteria)
Healthy Volunteers
healthy people welcome
Location
at UC Davis
Dates
study started
estimated completion
Principal Investigator
by Kathleen Angkustsiri, MD (ucdavis)

Description

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. Therefore, the investigators propose a pilot clinical trial to support the first randomized clinical trial of stimulant medication in children with DS+ADHD. The purpose of this study is to inform sample size estimates for the larger clinical trial. 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. Further, children will take part in the pilot methylphenidate clinical trial to inform measures retained and desired sample size for the future clinical trial.

Official Title

Evaluating Assessment and Medication Treatment of ADHD in Children With Down Syndrome

Details

The purpose of this study is to conduct a small pilot clinical trial of stimulant medication treatment (i.e., methylphenidate (MPH)) in children with DS+ADHD to inform sample size estimates and power calculations for a larger clinical trial. In sum, this study will directly address issue related to under-utilization of stimulant treatment in children with DS+ADHD, and it has the potential to significantly improve the outcomes of approximately 45,000 children with DS+ADHD nationwide. To achieve this, 30 children with DS+ADHD, between the ages of 6.00-17.99 years, will be invited to participate in a pilot clinical trial across two sites. Following pre-screening to determine study eligibility, children with DS+ADHD will be assessed at 14 different times points. The first pre-medication visit will include baseline intelligence, diagnostic, behavioral, cognitive, health, and functioning assessments. The second through sixth visits will begin Phase 1 of the pilot clinical trial, and during this time, participants will begin the lowest dose of MPH and titrate incrementally upward per pediatric guidelines based on the participant's height and weight. Weekly diagnostic and health assessments will be conducted to monitor the safety and efficacy of MPH during this phase. Further, this weekly monitoring will ultimately guide the selection of the participant's optimal dose. At the seventh visit, participants will enter Phase 2 of the pilot clinical trial where they will be randomized to receive an optimal dose of MPH (as determined by the assessments conducted throughout the titration phase) or the placebo. This visit will involve a repeat of most of the baseline measures. The eighth visit will initiate Phase 3 of the pilot clinical trial in which participants will crossover to the study intervention not previously assigned during Phase 2. For example, a participant who was assigned his or her optimal dose during Phase 2 will receive the placebo during Phase 3, and vice versa. Further, this visit will involve a repeat of the assessments conducted during Phase 2 which allows each participants to serve as his or her own control, contributing data both while on an optimal dose of MPH and while on the placebo. Prior to commencing Phase 4, MPH non-responders or placebo responders will be removed from the study and referred for non-study (clinical) treatment. Participants for whom MPH is judged to be effective and tolerable based on clinician ratings and parent/teacher reports will be invited to undergo an open label trial with their optimal MPH dose for a six-month maintenance period. During this phase, participants will undergo monthly diagnostic and health assessments to monitor the safety and efficacy of his or her optimal dose of MPH. The final visit (week 31) will include diagnostic, behavioral, cognitive, functioning, and health assessments to evaluate change across time.

Keywords

Down Syndrome ADHD Syndrome Methylphenidate Quillivant XR

Eligibility

You can join if…

Open to people ages 6-17

  • Documented diagnosis of DS through genetic testing
  • Ages 6.00-17.99 years
  • English is primary language
  • Meet criteria for ADHD on the KSADS
  • Meet criteria for ADHD on Vanderbilt (historically or currently)

You CAN'T join if...

  • Specific heart conditions including the following: (1) QTc on baseline ECG>470ms or QTC > 500 in patients with repaired CHD, as determined by ECG; (2) Brugada pattern as determined by ECG; (3) Baseline heart rate or systolic blood pressure > 2 SD above mean for age; (4) Complete AV block as determined by ECG; (5) History of aborted sudden cardiac death or unexplained syncope as determined by medical history; (6) History of a single ventricle as determined by medical history; (7) moderate or greater AV valve regurgitation as determined by ECHO; (8) moderate or greater ventricular dysfunction as determined by ECHO; (9) Pulmonary hypertension, defined as a mean pulmonary arterial pressure or right ventricular pressure without right ventricular outflow tract obstruction >25mmHg by ECHO; (10) Use of a pacemaker (11); Wolff Parkinson White/preventricular excitation, as determined by ECG; (12) Right ventricular enlargement/right axis deviation, as determined by ECG; (13) Intraventricular conduction delay >120ms in child >12 years old or >100ms in child < 8 years old, as determined by ECG in individuals with no prior history of cardiac surgery; (14) Right or left bundle branch block as determined by ECG; (15) Atrial, junctional, or ventricular tachyarrhythmia as determined by ECG; (16) Frequent premature ventricular contractions or premature atrial contractions as determined by ECG; (17) Abnormal T waves with inversion in V5 and/or V6, bizarre T wave morphology, notched biphasic T waves, or ST segment depression suggesting ischemia or inflammation as determined by ECG; . This can be verified in the participant's EPIC EMR.
  • Children with psychoses or bipolar disorder based on diagnostic interview with the parent.
  • Nonverbal mental age less than 36 months (3 years) per parent report.
  • 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.
  • Treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within 14 days.
  • Known hypersensitivity or allergic reactions to methylphenidate or product components such as bananas (due to bananas serving as an active ingredient in the formulation of the project's study intervention - Quillivant XR).
  • Since there is limited information regarding the safety of Quillivant XR during pregnancy, a pregnancy test will be conducted at the medical screen for female participants who have commenced the menstrual cycle. If pregnancy is indicated, the participant's parent/guardian will be notified, and the participants will be excluded from the study as a precautionary measure.
  • Moderate or severe obstructive sleep apnea (OSA) as rated by McGill index of 3 or higher.
  • Current use of ADHD stimulant or non-stimulant medications.

Locations

  • University of California Davis MIND Institute accepting new patients
    Sacramento California 95817 United States
  • Cincinnati Children's Hospital Medical Center accepting new patients
    Cincinnati Ohio 45229 United States

Lead Scientist at UC Health

  • Kathleen Angkustsiri, MD (ucdavis)
    Associate Professor, Pediatrics. Authored (or co-authored) 30 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Children's Hospital Medical Center, Cincinnati
ID
NCT04219280
Phase
Phase 1/2
Study Type
Interventional
Last Updated