Dose Clinical Trial of Guanfacine Extended Release for the Reduction of Aggression and Self-injuries Behavior Associated With Prader-Willi Syndrome

This is a placebo-controlled clinical trial to assess the utility of Guanfacine Extended Release (GXR) in the management of patients with Prader Willi Syndrome (PWS) who have significant aggression or self-injury. The purpose of this trial is to establish the safety of GXR with a specific focus on metabolic effects.

Study Overview

• Status: Withdrawn
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Other: Placebo; Drug: Guanfacine extended release (GXR)

Detailed Description

Prader-Willi syndrome is a genetic disorder due to loss of function of specific genes. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, the person becomes constantly hungry, which often leads to obesity and type 2 diabetes. Also, mild to moderate learning disability and behavioral problems are typical.

Guanfacine Extended Release (GXR), the investigational drug in this study would be the first study to evaluate the drug in patients with Prader Willi Syndrome. "Investigational" means it is not approved by the Food and Drug Administration (FDA) to treat Prader Willi Syndrome. However, Guanfacine Extended Released (GXR) is an FDA approved drug used to treat children and adolescents with hypertension and attention deficit hyperactivity disorder (ADHD). GXR is thought to respond to parts of the brain that lead to strengthening working memory, reducing distraction, improving attention and impulse control. GXR is generally considered safe for children as long as it is used according to the dosing instructions (up to 4mg) of a qualified medical professional.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 6 and 35 years of age
• diagnosis of PWS confirmed by genetic testing.
• rating of moderate or above on the Clinical Global Impression- Severity Scale will be required for entry.

Exclusion Criteria:

• Subjects with a positive pregnancy test, swallowing difficulty, and/or presenting with active psychosis or mania will be excluded.
• Individuals with pre-existing, clinically significant bradycardia (< 8 years: <64 bpm; 8 to 12 years: <59 bpm; 12 to 16 years: <53 bpm) or hypotension, defined as 5th percentile for height and gender,26 will be excluded from the study.
• Subjects receiving antipsychotic medications due to a documented history of psychosis or bipolar disorder will be allowed to continue taking the medication without dosage modification.
• Growth hormone, thyroid hormone replacement treatment, and non-psychiatric medicines will be allowed to continue.
• N-Acetyl Cysteine and anticonvulsant medication (only if prescribed for seizures) will be allowed to continue, with specific instructions to not make any dosage changes during the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Placebo	Other: Placebo; Placebo will be administered same times as GXR
Experimental: GXR; Immediately following the 8-week blinded randomized trial, an 8-week open-label continuation phase will be pursued to further define efficacy and tolerability of GXR, and to establish its safety with specific focus on metabolic profile.	Drug: Guanfacine extended release (GXR); The starting dose for all subjects will be 1 mg per day. If the medication is well-tolerated, the dose can be raised to 2 mg until day 28 and increased to 3mg for the remaining 4 weeks in the trial. The dose schedule will not be fixed; the treating clinician can delay a planned increase or lower the dose to manage adverse effects. At week 8, the study will be unblinded and subjects will continue treatment for 8 more weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGI-I scale rating	A positive clinical response will be determined by a rating of 1 or 2 (Very much/Much improved) on the CGI-I scale at the end of the blinded trial.	19 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist	Consists of 2 subscales; irritability (15 items) and hyperactivity/noncompliance (16 items).	19 Weeks
Self-Injury Trauma scale	SHI scores of 5 or greater were found to be indicative of borderline personality disorder. Part 1 is ranking based on the number of wounds 1=one would (common in a mild SIB but rare in a severe case) 2=two or four wounds (common) and 3=five or more wounds (rare). Injury severity is scored on a subjective basis with labels such as "mild" "moderate" and "severe" accompanied by descriptions of the observed state of the anatomy. Part 3 is the Estimate of Current Risk.	19 Weeks
Modified Overt Aggression Scale	four-part behavior rating scale used to evaluate and document the "frequency and severity" of aggressive episodes.[1] The rating scale is made up of four categories; verbal aggression, aggression against objects, aggression against self, and aggression against others	19 Weeks

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Winthrop University Hospital
• Investigators: Principal Investigator: Deepan Singh, MD, New York Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): August 21, 2020
• Study Completion (Actual): August 21, 2020

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 26, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Aggression; Syndrome; Prader-Willi Syndrome; Self-Injurious Behavior; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Guanfacine
• Other Study ID Numbers: 19-00936

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No