Mass General - Division of Clinical Research

Conditions

• Hyperactivity in Children with Down Syndrome
• Impulsivity in Children with Down Syndrome

Eligibility

Eligible Ages

Between 6 Years and 12 Years

Eligible Genders

All

Accepts Healthy Volunteers

Yes

Criteria

Inclusion:

1. Parent/Legal Guardian can understand the consent process and is willing to provide
informed consent/HIPAA authorization prior to the conduct of any study-related
procedures. When applicable, the minor participant is willing to provide assent.

2. Participant has clinical diagnosis of non-mosaic DS.

3. Participant is between 6 and 12 years of age (inclusive) at time of consent.

4. Participant weight is ≥ 25 kg.

5. Participant has clinically significant symptoms of hyperactivity, inattention and
impulsivity manifested as minimum scores of the following rating scales within 30
days of randomization:

1. A minimum score of 18 on the parent-reported ABC-H subscale, AND

2. A minimum score of moderate or greater (≥ 4) on the clinician reported Clinical
Global Impression Severity (CGI-S) score specific to hyperactivity, inattention
and impulsivity behaviors.

6. Participant has co-morbid medical screening and clearance to proceed with a
non-stimulant medication trial with GIR within 30 days of randomization.

7. Participant is willing and able to comply with study procedures, including adherence
to medication dosing schedule.

Exclusion:

1. Participant has received guanfacine (any formulation) within 30 days of
randomization.

2. Participant has received any of the following concomitant medication classes within
30 days of randomization:

1. Strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan,
grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir,
mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir,
telaprevir, telithromycin, and voriconazole)

2. Strong CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin,
and St. John's wort)

3. Participant has a psychiatric comorbidity, such as major depressive disorder,
bipolar disorder, obsessive-compulsive disorder, or a psychotic disorder, that
requires a pharmacological treatment other than guanfacine

4. For participants ≥ 8 years old at the time of consent, participant has a history of
suicidality or positive screen on Ask Suicide-Screening Questions (asQ) Tool.

5. Participant is currently in or plans to participate in another interventional study.

6. Participant has a known hypersensitivity to guanfacine.

7. Participant has had a previous guanfacine treatment failure, as determined by their
primary treating physician.

8. Participant has had a change in another medication intended to treat symptoms of
hyperactivity, inattention, and impulsivity within the last 2 weeks.

9. Participant has had a seizure within the last 6 months.

10. Participant has had a change in their anti-convulsant dose within the last 4 weeks.

11. Participant has a cardiac-related condition including:

1. Significant symptomatic bradycardia;

2. 2nd degree or 3rd degree (complete) heart block;

3. Baseline heart rate (HR) or systolic blood pressure (BP) > 2 standard
deviations (SD) below mean for age as determined by medical examination;

4. History of aborted sudden cardiac death, unexplained syncope or near syncope,
or historical use of a pacemaker as determined by medical history will require
clearance by cardiology prior to enrollment;

5. Known history of congenital heart disease which requires ongoing care for
monitoring or management will require clearance by cardiology prior to
enrollment.

12. Participant has a history of untreated severe obstructive sleep apnea defined as
obstructive apnea hypopnea index (OAHI) ≥ 10 events per hour or aortic regurgitation
(AR). Participants with an OAHI index > 10/hr are eligible if managed with
continuous positive airway pressure (CPAP).

13. Participant has untreated thyroid disease.

14. Participant has a known hepatic impairment defined as aspartate aminotransferase
(AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN) for
age.

15. Participant has known impending or renal failure defined as:

1. Anuria diagnosed within 12 hours prior to enrollment;

2. Requiring renal replacement therapy.

16. Participant is pregnant.

17. Participant has any condition which would make the participant, in the opinion of
the investigator, unsuitable for the study.

Recruiting Locations

Study Contact

Detailed Description

This is a randomized, double-blind, placebo-controlled flexibly dosed trial of guanfacine immediate release (GIR) in children with Down syndrome (DS) and symptoms of hyperactivity, inattention, and impulsivity. Participants will undergo a screening period of up to 29 days. Eligible participants meeting study criteria will be randomized 2:1 GIR or placebo. There are a total of up to 4 in person visits (screening, baseline, at Week 4, and at Week 8). Participants will receive GIR or placebo for up to 8 weeks. Weekly dose escalation will be determined via a telephone assessment at Weeks 1-3 and Weeks 4-7. Unmasking of participant and site staff will occur at the week 8, in-person visit. After unmasking, participants who were randomized to receive GIR will be given the option to 1) remain on GIR and to transition to open-label GIR per standard of care or 2) taper off of GIR. A Telephone Safety Assessment will be conducted for all participants, at 5 (+2) days after final study product administration. Blood specimens will be collected at the Week 4 and Week 8 visits for Pharmacokinetic (PK) analyses and lab assessments. Participants will be asked to keep a daily study diary and will complete study measures at screening/baseline, Week 4 and Week 8. Parents/Caregivers will need to complete the Study Diary during the bridge/taper period for those who are in the GIR arm.