Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS) (HYP01)

April 16, 2024 updated by: Rachel G. Greenberg, MD, MB, MHS
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: Guanfacine Hydrochloride Immediate Release
0.5 mg capsules
Placebo Comparator: 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.
Drug: Placebo
Matching placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
Time Frame: Baseline to Week 8
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
Time Frame: Baseline to Week 4
Change from baseline to Week 4 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 4
Safety of GIR (guanfacine immediate release)
Time Frame: Baseline through Week 8
Number of participants with adverse events (AEs), serious adverse events (SAEs), or events of special interest (ESIs).
Baseline through Week 8
Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 4
Time Frame: Baseline to Week 4
CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
Baseline to Week 4
Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 8
Time Frame: Baseline to Week 8
CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
Baseline to Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rachel G. Greenberg, MD, MB, MHS

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Emmes Company, LLC

Investigators

  • Principal Investigator: Rachel Greenberg, DCRI

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

November 1, 2025

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

July 31, 2023

First Submitted That Met QC Criteria

September 11, 2023

First Posted (Actual)

September 18, 2023

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00111256
  • HHSN275201800003I (Other Grant/Funding Number: National Institute of Child Health and Human Development)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data collected is uploaded into the National Institute of Health Data Repository (DASH) at the end of the study (de-identified).

IPD Sharing Time Frame

Data will be uploaded to the repository within 2 years of study completion. It will be maintained in the repository indefinitely.

IPD Sharing 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

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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