Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)

NCT06042257 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: Pro00111256HHSN275201800003I
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 14

Brief Summary

The primary 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.

Conditions

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

Keywords

hyperactivity; impulsivity; inattention

Outcome Measures

Primary Outcomes (1)

• Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core

  Change from baseline to Week 8 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient's behavior in last 4 weeks.

  Baseline to Week 8

Secondary Outcomes (4)

• Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core

  Baseline to Week 4

• Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 4

  Baseline to Week 4

• Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 8

  Baseline to Week 8

• Safety of GIR (guanfacine immediate release)

  Baseline through Week 8

Study Arms (2)

Guanfacine Hydrochloride Immediate Release

ACTIVE COMPARATOR

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.

Drug: Guanfacine Hydrochloride Immediate Release

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Guanfacine Hydrochloride Immediate Release DRUG

0.5 mg capsules

Guanfacine Hydrochloride Immediate Release

Placebo DRUG

Matching placebo capsule

Placebo

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Participant has clinical diagnosis of non-mosaic DS.
• Participant is between 6 and 12 years of age (inclusive) at time of consent.
• Participant weight is ≥ 25 kg.
• Participant has clinically significant symptoms of hyperactivity, inattention and impulsivity manifested as minimum scores of the following rating scales within 30 days of randomization:
• A minimum score of 18 on the parent-reported ABC-H subscale, AND
• 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.
• Participant has co-morbid medical screening and clearance to proceed with a non-stimulant medication trial with GIR within 30 days of randomization.
• Participant is willing and able to comply with study procedures, including adherence to medication dosing schedule.

You may not qualify if:

• Participant has received guanfacine (any formulation) within 30 days of randomization.
• Participant has received any of the following concomitant medication classes within 30 days of randomization:
• 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)
• Strong CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and St. John's wort)
• 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
• 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.
• Participant is currently in or plans to participate in another interventional study.
• Participant has a known hypersensitivity to guanfacine.
• Participant has had a previous guanfacine treatment failure, as determined by their primary treating physician.
• Participant has had a change in another medication intended to treat symptoms of hyperactivity, inattention, and impulsivity within the last 2 weeks.
• Participant has had a seizure within the last 6 months.
• Participant has had a change in their anti-convulsant dose within the last 4 weeks.
• Participant has a cardiac-related condition including:
• Significant symptomatic bradycardia;
• nd degree or 3rd degree (complete) heart block;

Sponsors & Collaborators

• Rachel G. Greenberg, MD, MB, MHS: lead
• The Emmes Company, LLC: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (14)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Ann and Robert H. Lurie Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Lexington, Massachusetts, 02421, United States

Location

Atrium Health-Wake Forest School of Medicine

Charlotte, North Carolina, 28204, United States

Location

Duke University Hospital

Durham, North Carolina, 27705, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Virginia Center for Children

Richmond, Virginia, 23220, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

University of Wisconsin Madison

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Spasm; Impulsive Behavior

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Rachel Greenberg

  DCRI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: A masked investigational pharmacist or designee will dispense study product according to randomization treatment assignments. All other site staff as well as participants and parents/legal guardians will also be masked for up to 8 weeks while the study participant is receiving study product. Participants, parents/legal guardians, site staff, and study administrators will be unmasked at the 8 week study visit. Emergency unmasking may occur at any time throughout the study in the event that knowledge of the actual treatment is absolutely essential for further management of the participant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: Participants will be randomized 2:1 to GIR or placebo.

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: September 18, 2023
• Study Start: December 9, 2024
• Primary Completion: May 17, 2025
• Study Completion: August 12, 2025
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be uploaded to the repository within 2 years of study completion. It will be maintained in the repository indefinitely.
• Access Criteria: In order to have access, researchers have to complete a Data access request. NICHD will review the request and either approve or deny it. IRB approval must be obtained by the researcher to access the data. https://dash.nichd.nih.gov/Resource/DataRequestChecklist

Locations

US (14)