Hyperactivity in Children With Down SyndromePhase 2HYP01NCT06042257
Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)
A Phase 2 study testing Guanfacine Hydrochloride Immediate Release in people with Hyperactivity in Children With Down Syndrome and Impulsivity in Children With Down Syndrome, run by Rachel G. Greenberg, MD, MB, MHS at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperactivity in Children With Down Syndrome, Impulsivity in Children With Down Syndrome
- What is being tested?
- Guanfacine Hydrochloride Immediate Release
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 14 sitesUnited States
- Study dates
- 9 Dec 2024to 12 Aug 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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;
- 2nd degree or 3rd degree (complete) heart block;
- Baseline heart rate (HR) or systolic blood pressure (BP) > 2 standard deviations (SD) below mean for age as determined by medical examination;
- 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;
- Known history of congenital heart disease which requires ongoing care for monitoring or management will require clearance by cardiology prior to enrollment.
- 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).
- Participant has untreated thyroid disease.
- Participant has a known hepatic impairment defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN) for age.
- Participant has known impending or renal failure defined as:
- Anuria diagnosed within 12 hours prior to enrollment;
- Requiring renal replacement therapy.
- Participant is pregnant.
- Participant has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Akron Children's Hospital
Akron, Ohio, 44308
Emory University
Atlanta, Georgia, 30322
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Boston Children's Hospital
Boston, Massachusetts, 02115
Atrium Health-Wake Forest School of Medicine
Charlotte, North Carolina, 28204
Ann and Robert H. Lurie Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Duke University Hospital
Durham, North Carolina, 27705
University of Iowa
Iowa City, Iowa, 52242
Massachusetts General Hospital
Lexington, Massachusetts, 02421
University of Wisconsin Madison
Madison, Wisconsin, 53792
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Virginia Center for Children
Richmond, Virginia, 23220
University of Washington
Seattle, Washington, 98195
About this study
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.
Read the 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. Participant data will be collected via a daily study diary and study measures completed 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.
- Being tested
- Guanfacine Hydrochloride Immediate Release, Placebo
- Keywords
- hyperactivity, impulsivity, inattention
- Medical subject headings
- Spasm, Impulsive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Guanfacine Hydrochloride Immediate ReleaseDrug
0.5 mg capsules
PlaceboDrug
Matching placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 8
Secondary outcomes (4)
Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
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.
Measured: Baseline to Week 4
Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at 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.
Measured: Baseline to Week 4
Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at 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.
Measured: Baseline to Week 8
Safety of GIR (guanfacine immediate release)
Number of participants with adverse events (AEs), serious adverse events (SAEs), or events of special interest (ESIs).
Measured: Baseline through Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2023
- Study start9 Dec 2024
- Primary completion17 May 2025
- Study completion12 Aug 2025
Why it stopped: Study was stopped after careful review of product manufacturing needs and available resources. Decision reflects consideration of feasibility, enrollment challenges, and overall program goals.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyperactivity in Children With Down SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized 2:1 to GIR or placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rachel G. Greenberg, MD, MB, MHS
- Sponsor type
- University, hospital or other
- Collaborators
- The Emmes Company, LLC, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Rachel G. Greenberg, MD, MB, MHS, Duke University
- Investigators
- Rachel Greenberg, Principal investigator, DCRI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06042257
- Sponsor's protocol ID
- Pro00111256
- Other IDs
- HHSN275201800003I
- Acronym
- HYP01
- Status last verified
- Apr 2026
- First submitted
- 31 Jul 2023
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data is uploaded into the National Institute of Health Data and Specimen Hub (DASH) at the end of the study (de-identified). Samples are also shared with DASH for future use.
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)
- ClinicalTrials.gov ID
- NCT06042257
- Acronym / sponsor ID
- HYP01 / Pro00111256
- Keywords
- hyperactivity, impulsivity, inattention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was stopped after careful review of product manufacturing needs and available resources. Decision reflects consideration of feasibility, enrollment challenges, and overall program goals.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Rachel G. Greenberg, MD, MB, MHSUniversity, hospital or other
- Collaborators
- The Emmes Company, LLC, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 9 Dec 2024 (actual)
- Primary completion
- 17 May 2025 (actual)
- Study completion
- 12 Aug 2025 (actual)
- First posted
- 18 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. Participant data will be collected via a daily study diary and study measures completed 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomized 2:1 to GIR or placebo.
| Arm | Type | Receives |
|---|---|---|
| Guanfacine Hydrochloride Immediate Release | Active comparator | Drug: Guanfacine Hydrochloride Immediate ReleaseEligible 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. |
| Placebo | Placebo comparator | Drug: PlaceboEligible 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. |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (26 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Guanfacine Hydrochloride Immediate Release0.5 mg capsules | Drug | Guanfacine Hydrochloride Immediate Release |
| PlaceboMatching placebo capsule | Drug | Placebo |
Primary outcome
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.
4 secondary outcomes
Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
Time frame: Baseline to Week 4
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
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
Safety of GIR (guanfacine immediate release)
Time frame: Baseline through Week 8
Results and safety
The study was stopped early (reason given: Study was stopped after careful review of product manufacturing needs and available resources. Decision reflects consideration of feasibility, enrollment challenges, and overall program goals.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Individual participant dataSharing planned: Yes. All data is uploaded into the National Institute of Health Data and Specimen Hub (DASH) at the end of the study (de-identified). Samples are also shared with DASH for future use.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Greenberg principal investigator
DCRI
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Guanfacine Hydrochloride Immediate Release in people with Hyperactivity in Children With Down Syndrome and Impulsivity in Children With Down Syndrome, run by Rachel G. Greenberg, MD, MB, MHS at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study was stopped after careful review of product manufacturing needs and available resources. Decision reflects consideration of feasibility, enrollment challenges, and overall program goals.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core (time frame: Baseline to Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.