Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS) (HYP01)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT06042257 |
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Recruitment Status :
Not yet recruiting
First Posted : September 18, 2023
Last Update Posted : April 17, 2024
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Sponsor:
Rachel G. Greenberg, MD, MB, MHS
Collaborators:
The Emmes Company, LLC
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Rachel G. Greenberg, MD, MB, MHS, Duke University
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hyperactivity in Children With Down Syndrome Impulsivity in Children With Down Syndrome | Drug: Guanfacine Hydrochloride Immediate Release Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Participants will be randomized 2:1 to GIR or placebo. |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Masking Description: | 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. |
| Primary Purpose: | Treatment |
| Official Title: | Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS) |
| Estimated Study Start Date : | May 2024 |
| Estimated Primary Completion Date : | November 2025 |
| Estimated Study Completion Date : | February 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Down syndrome
MedlinePlus related topics:
Down Syndrome
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Guanfacine Hydrochloride Immediate Release
0.5 mg capsules |
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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.
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Drug: Placebo
Matching placebo capsule |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
- 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.
- 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.
- 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).
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| Ages Eligible for Study: | 6 Years to 12 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion:
- 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.
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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.
Exclusion:
- Participant has received guanfacine (any formulation) within 30 days of randomization.
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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.
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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.
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06042257
Contacts
| Contact: Christie Milleson | 919.668.6055 | christie.milleson@duke.edu | |
| Contact: Zoe Sund | 202-573-2673 | zoe.sund@duke.edu |
Locations
| United States, Arizona | |
| Phoenix Childrens Hospital | |
| Phoenix, Arizona, United States, 85016 | |
| Contact: Sean Patino 602-933-0641 spatino@phoenixchildrens.com | |
| Contact: Lalaine Dungca 602-933-0682 ldungca@phoenixchildrens.com | |
| Principal Investigator: Dannah Raz | |
| United States, Georgia | |
| Emory University | |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Jean Luann McColl jean.luan@emory.edu | |
| Contact: Amy Talboy amy.talboy@emory.edu | |
| Principal Investigator: Amy Talboy | |
| Sub-Investigator: Stephanie Wechsler | |
| United States, Illinois | |
| Ann and Robert H. Lurie Hospital of Chicago | |
| Chicago, Illinois, United States, 60611 | |
| Contact: Ally Byrd 312-227-0067 albyrd@luriechildrens.org | |
| Contact: Rachel Follmer rfollmer@luriechildrens.org | |
| Principal Investigator: Rachel Follmer | |
| United States, Iowa | |
| University of Iowa | |
| Iowa City, Iowa, United States, 52242 | |
| Contact: Beverly Vermace beverly-vermace@uiowa.edu | |
| Contact: Marcio Leyser marcio-leyser@uiowa.edu | |
| Principal Investigator: Marcio Leyser | |
| Sub-Investigator: Deborah Lin-Dyken | |
| United States, Maryland | |
| Kennedy Krieger Institute | |
| Baltimore, Maryland, United States, 21205 | |
| Contact: Andrea De La Torre 667-205-4244 delatorreap@kennedykrieger.org | |
| Contact: Karen Chen 667-205-4393 chenk@kennedykrieger.org | |
| Principal Investigator: George Capone | |
| Sub-Investigator: Mihee Bay | |
| United States, Massachusetts | |
| Boston Children's Hospital | |
| Boston, Massachusetts, United States, 02115 | |
| Contact: Meaghan Dyer meaghan.dyer@childrens.harvard.edu | |
| Contact: Marie Canty marie.canty@childrens.harvard.edu | |
| Principal Investigator: Nicole Baumer | |
| Sub-Investigator: Sabrina Sargado | |
| Massachusetts General Hospital | |
| Lexington, Massachusetts, United States, 02421 | |
| Contact: Alexander Cordova acordova1@mgh.harvard.edu | |
| Contact: Heli Patel hpatel24@mgh.harvard.edu | |
| Principal Investigator: Michelle Palumbo | |
| United States, North Carolina | |
| Atrium Health-Wake Forest School of Medicine | |
| Charlotte, North Carolina, United States, 28204 | |
| Contact: CynDavia McKoy cyndavia.mckoy@atriumhealth.org | |
| Contact: Mohammed Saifelnasr 704-446-4804 saifelnasr.mohamed@atriumhealth.org | |
| Principal Investigator: Yasmin Senturias | |
| Sub-Investigator: Christine Turley | |
| Duke University Hospital | |
| Durham, North Carolina, United States, 27705 | |
| Contact: Brittany Nave 919-684-8087 brittany.nave@duke.edu | |
| Contact: Joan Jasien, MD joan.jasien@duke.edu | |
| Principal Investigator: Joan Jasien | |
| United States, Ohio | |
| Akron Children's Hospital | |
| Akron, Ohio, United States, 44308 | |
| Contact: Alia Brandenburg 330-543-3193 abrandenburg@akronchildrens.org | |
| Contact: Josselyn Copenger jcoppenger@akronchildrens.org | |
| Principal Investigator: Diane Langkamp | |
| Cincinnati Children's Hospital | |
| Cincinnati, Ohio, United States, 45229 | |
| Contact: Olivia Roberson 513-636-1528 olivia.roberson@cchmc.org | |
| Contact: Kellie Voth 513-636-0674 kellie.ramsdale@cchmc.org | |
| Principal Investigator: Tonya Froehlich | |
| Sub-Investigator: Anna Esbensen | |
| United States, Washington | |
| University of Washington | |
| Seattle, Washington, United States, 98195 | |
| Contact: Stephanie Lammers stephanie.lammers@seattlechildrens.org | |
| Contact: Victoria Weiss victoria.weiss@seattlechildrens.org | |
| Principal Investigator: Julia Mattson | |
| United States, Wisconsin | |
| University of Wisconsin Madison | |
| Madison, Wisconsin, United States, 53792 | |
| Contact: Courtney Oliver 906-251-0353 coliver4@wisc.edu | |
| Contact: Maria Stanley mastanley@pediatrics.wisc.edu | |
| Principal Investigator: Maria Stanley | |
Sponsors and Collaborators
Rachel G. Greenberg, MD, MB, MHS
The Emmes Company, LLC
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
| Principal Investigator: | Rachel Greenberg | DCRI |
| Responsible Party: | Rachel G. Greenberg, MD, MB, MHS, Associate Professor of Pediatrics, Duke University |
| ClinicalTrials.gov Identifier: | NCT06042257 |
| Other Study ID Numbers: |
Pro00111256 HHSN275201800003I ( Other Grant/Funding Number: National Institute of Child Health and Human Development ) |
| First Posted: | September 18, 2023 Key Record Dates |
| Last Update Posted: | April 17, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | All data collected is uploaded into the National Institute of Health Data Repository (DASH) at the end of the study (de-identified). |
| Supporting Materials: |
Study Protocol Informed Consent Form (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 |
| URL: | https://dash.nichd.nih.gov/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Rachel G. Greenberg, MD, MB, MHS, Duke University:
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hyperactivity impulsivity inattention |
Additional relevant MeSH terms:
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Hyperkinesis Down Syndrome Syndrome Impulsive Behavior Disease Pathologic Processes Dyskinesias Neurologic Manifestations Nervous System Diseases Intellectual Disability Neurobehavioral Manifestations Abnormalities, Multiple |
Congenital Abnormalities Chromosome Disorders Genetic Diseases, Inborn Guanfacine Antihypertensive Agents Adrenergic alpha-2 Receptor Agonists Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |