Guanfacine for Hyperactivity in Down Syndrome
(HYP01 Trial)
Recruiting in Palo Alto (17 mi)
+14 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Rachel G. Greenberg, MD, MB, MHS
Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers
Disqualifiers: Psychiatric disorders, Cardiac conditions, Seizures, others
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications, specifically strong CYP3A4 inhibitors and inducers, at least 30 days before starting the study. If you are on medications for hyperactivity, inattention, or impulsivity, you should not have changed them in the last 2 weeks before joining the trial.
What data supports the effectiveness of the drug Guanfacine Hydrochloride Immediate Release for hyperactivity in Down Syndrome?
Research shows that guanfacine, particularly in its extended-release form, is effective in reducing symptoms of hyperactivity and inattention in children and adolescents with ADHD. This suggests it might also help with similar symptoms in individuals with Down Syndrome.
12345Is guanfacine safe for humans?
Guanfacine, used for conditions like ADHD, has been generally safe in humans, but some people experience side effects like drowsiness, headache, and fatigue. It can cause mild changes in heart rate and blood pressure, so monitoring is recommended, especially for those with heart issues.
12467How is the drug Guanfacine Hydrochloride Immediate Release unique for treating hyperactivity in Down Syndrome?
Guanfacine Hydrochloride Immediate Release is unique because it is a centrally acting α2-adrenergic agonist, which means it works by affecting certain receptors in the brain to help reduce hyperactivity and impulsivity. This mechanism is different from other treatments for hyperactivity, which may not target these specific brain receptors.
15689Eligibility Criteria
This trial is for children aged 6-12 with Down syndrome who are hyperactive or impulsive. They must weigh at least 25 kg and have a certain level of severity in their symptoms as reported by parents and clinicians. Participants should not have taken guanfacine or strong CYP3A4 inhibitors recently.Inclusion Criteria
I weigh at least 25 kg.
I have significant symptoms of ADHD as confirmed by recent tests.
I have been diagnosed with Down syndrome that is not mosaic.
+4 more
Exclusion Criteria
I have taken guanfacine in the last 30 days.
Participant has received any of the following concomitant medication classes within 30 days of randomization: Strong CYP3A4 inhibitors, Strong CYP3A4 inducers, Participant has a psychiatric comorbidity 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, 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 Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
1 visit (in-person)
Treatment
Participants receive guanfacine immediate release (GIR) or placebo for up to 8 weeks with weekly dose escalation determined via telephone assessment
8 weeks
4 visits (in-person), 6 visits (telephone)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including a Telephone Safety Assessment 5 days after final study product administration
1 week
1 visit (telephone)
Open-label extension (optional)
Participants who received GIR may opt to remain on GIR and transition to open-label GIR per standard of care or taper off
Participant Groups
The study tests if Guanfacine Hydrochloride Immediate Release (GIR) can help manage hyperactivity/impulsivity and inattention over an 8-week period, compared to a placebo (a pill without any medicine).
2Treatment groups
Active Control
Placebo Group
Group I: Guanfacine Hydrochloride Immediate ReleaseActive Control1 Intervention
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 II: PlaceboPlacebo Group1 Intervention
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.
Guanfacine Hydrochloride Immediate Release is already approved in United States, United States, European Union, European Union for the following indications:
🇺🇸 Approved in United States as Tenex for:
- Hypertension
- Attention Deficit Hyperactivity Disorder (ADHD)
🇺🇸 Approved in United States as Intuniv for:
- Attention Deficit Hyperactivity Disorder (ADHD)
🇪🇺 Approved in European Union as Intuniv for:
- Attention Deficit Hyperactivity Disorder (ADHD)
🇪🇺 Approved in European Union as Paxneury for:
- Attention Deficit Hyperactivity Disorder (ADHD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale University School of MedicineNew Haven, CT
Virginia Center for ChildrenRichmond, VA
University of WashingtonSeattle, WA
University of Wisconsin MadisonMadison, WI
More Trial Locations
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Who Is Running the Clinical Trial?
Rachel G. Greenberg, MD, MB, MHSLead Sponsor
The Emmes Company, LLCIndustry Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Collaborator
References
Guanfacine extended release in the treatment of attention deficit hyperactivity disorder in children and adolescents. [2017]Extended-release guanfacine (Intuniv) is a novel long-acting, once-daily formulation of guanfacine indicated for attention deficit hyperactivity disorder (ADHD) in 6 to 17 year old children and adolescents. In doses 1 to 4 mg/day, guanfacine extended release (GXR) significantly improves the symptoms of inattention and hyperactivity-impulsivity in ADHD youngsters compared with placebo. Because of different pharmacokinetics, GXR is not substitutable on a mg-for-mg basis with immediate release guanfacine. Although extended release guanfacine does not demonstrate clinically significant ECG changes, mild slowing of the heart rate and some lowering of SBP and DBP does occur and requires vital sign monitoring during treatment. Children with a clinically significant cardiovascular history are not eligible for GXR therapy. Future research is exploring GXR effectiveness in ADHD complicated by oppositional defiant symptoms, ADHD complicated by tic disorders, posttraumatic stress disorders, and impulsive aggression in ADHD youngsters.
Effects of guanfacine extended release on oppositional symptoms in children aged 6-12 years with attention-deficit hyperactivity disorder and oppositional symptoms: a randomized, double-blind, placebo-controlled trial. [2022]To evaluate the efficacy and safety of guanfacine extended release (XR, Intuniv; Shire Development Inc., Wayne, PA, USA) in the treatment of oppositional symptoms in children aged 6-12 years with a diagnosis of attention-deficit hyperactivity disorder (ADHD) and the presence of oppositional symptoms.
Safety and efficacy of guanfacine extended-release in adults with attention-deficit/hyperactivity disorder: an open-label, long-term, phase 3 extension study. [2022]To assess the safety and efficacy of long-term administration of guanfacine extended-release (GXR) in adults with attention-deficit/hyperactivity disorder (ADHD).
A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. [2022]To examine efficacy, tolerability, and safety of guanfacine extended release (GXR; ≤4 mg/d) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years of age with suboptimal, but partial, response to psychostimulant alone.
Efficacy of guanfacine extended release in the treatment of combined and inattentive only subtypes of attention-deficit/hyperactivity disorder. [2021]Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness.
Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. [2018]Data are reported from SPD503-318, a phase 3, open-label, safety study of guanfacine extended release (GXR) in European children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants received dose-optimized GXR (1-7 mg/day) for up to 2 years. Of 215 enrolled participants, 214 were included in the safety population and 133 completed the study. Participants' mean age was 11.7 years and 73.8% were male. Overall, 177 participants (82.7%) experienced a treatment-emergent adverse event (TEAE). TEAEs reported in at least 10% of participants were somnolence (36.0%), headache (28.5%), fatigue (20.1%), and nasopharyngitis (11.7%). Serious TEAEs were reported in 4.7% of participants and TEAEs leading to discontinuation were reported in 3.3% of participants. There were no deaths. Mean z-scores for BMI were stable throughout the study. The incidence of sedative TEAEs (somnolence, sedation, and hypersomnia) peaked during week 3 and decreased thereafter. Small changes from baseline to the final assessment in mean supine pulse [- 5.5 bpm (standard deviation, 12.98)] and blood pressure [systolic, 0.6 mmHg (9.32); diastolic, 0.2 mmHg (9.17)] were reported. ADHD symptoms initially decreased and remained significantly lower than baseline at study endpoint. At the final assessment, the mean change in ADHD-RS-IV total score from baseline was - 19.8 (standard error of mean, 0.84; nominal p
Use of ECG restitution (beat-to-beat QT-TQ interval analysis) to assess arrhythmogenic risk of QTc prolongation with guanfacine. [2021]Guanfacine (Intuniv) is a centrally active alpha-2A adrenergic agonist for the new indication of attention-deficit/hyperactivity disorder. QTc (QTcF and QTcNi) was prolonged at both therapeutic (4 mg) and supratherapeutic (8 mg) doses of a thorough QT study even though guanfacine has had a safe clinical history of over 3 million prescriptions for the treatment of hypertension. In an attempt to understand this disparity, retrospective evaluation of the continuous ECG data utilized dynamic beat-to-beat and ECG restitution analyses was performed.
Focus on Guanfacine Extended-release: A Review of its Use in Child and Adolescent Psychiatry. [2021]To review the basic pharmacology and published literature regarding use of guanfacine extended-release (GXR) for the treatment of attention deficit/hyperactivity disorder in children and adolescents.
An overdose of extended-release guanfacine. [2013]Extended-release guanfacine is a centrally acting α2-adrenergic agonist that was recently approved for treatment of attention-deficit/hyperactivity disorder. The following is a case discussion of a 12-year-old boy with attention-deficit/hyperactivity disorder and Tourette syndrome, who presented 18 hours after ingestion of 3 times his usual dose of extended-release guanfacine. On presentation, he was lethargic, bradycardic, and hypertensive with an otherwise nonfocal neurological examination. He remained hypertensive until administration of an intravenous antihypertensive agent (nicardipine) 24 hours after ingestion. After cessation of the calcium-channel blocker, he continued to have intermittent episodes of symptomatic hypotension for the next 2½ days. This extremely protracted course of hypertension followed by prolonged symptomatic hypotension is rare with ingestions of centrally acting α2-adrenergic agonists. As this drug is increasingly prescribed for treatment of a disease with increasing prevalence, it is imperative that emergency physicians become familiar with the varying presentations of its toxicity.