Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)

NCT ID: NCT06042257

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-09
• Study Completion Date: 2026-07-31

Brief Summary

The purpose of this study is to determine efficacy of guanfacine immediate release (GIR) for the treatment of hyperactivity/impulsivity and inattention in children 6-12 years of age with Down syndrome (DS) after 8 weeks of treatment.

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.

Conditions

Hyperactivity in Children With Down Syndrome; Impulsivity in Children With Down Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Guanfacine Hydrochloride Immediate Release

Eligible participants will receive GIR for up to 8 weeks. The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.

Group Type: ACTIVE_COMPARATOR

Guanfacine Hydrochloride Immediate Release

Intervention Type: DRUG

0.5 mg capsules

Placebo

Eligible participants will receive Placebo for up to 8 weeks.The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo capsule

Interventions

Guanfacine Hydrochloride Immediate Release

0.5 mg capsules

Intervention Type: DRUG

Placebo

Matching placebo capsule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Rachel G. Greenberg, MD, MB, MHS

OTHER

Sponsor Role: lead

Responsible Party

Rachel G. Greenberg, MD, MB, MHS

Associate Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Rachel Greenberg

Role: PRINCIPAL_INVESTIGATOR

DCRI

Locations

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Emory University

Atlanta, Georgia, United States

Ann and Robert H. Lurie Hospital of Chicago

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Massachusetts General Hospital

Lexington, Massachusetts, United States

Atrium Health-Wake Forest School of Medicine

Charlotte, North Carolina, United States

Duke University Hospital

Durham, North Carolina, United States

Akron Children's Hospital

Akron, Ohio, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Virginia Center for Children

Richmond, Virginia, United States

University of Washington

Seattle, Washington, United States

University of Wisconsin Madison

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

HHSN275201800003I

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Pro00111256

Identifier Type: -

Identifier Source: org_study_id