Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome (PWS-GXR)

March 13, 2023 updated by: Maimonides Medical Center

A Double Blind, Placebo Controlled, Fixed-Flexible Dose Clinical Trial of Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome

This is a placebo-controlled clinical trial to assess whether Guanfacine Extended Release (GXR) reduces aggression and self injurious behavior in individuals with Prader Willi Syndrome (PWS). In addition, the study will establish the safety of GXR with a specific focus on metabolic effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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. Aggression, oppositional behavior, and temper tantrums frequently occur in patients with PWS. PWS also has a high prevalence of self-injury, repetitive behavior, impulsivity, over-activity, and mild to moderate learning disability.

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.

This randomized, double-blind, placebo-controlled clinical trial aims to determine whether guanfacine extended release (GXR) reduces aggression and self-injury compared to placebo in individuals with PWS with moderate to severe aggressive and/or self-injurious behavior. In addition, GXR's tolerability will be assessed by systematically evaluating and documenting adverse events.

Study Type

Interventional

Enrollment (Anticipated)

33

Phase

  • Phase 4

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

  • United States
    • New York
      • Brooklyn, New York, United States, 11219
        • Recruiting
        • Maimonides Medical Center
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Theresa Jacob, PhD, MPH

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

6 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of PWS confirmed by genetic testing documentation
  • Rating of moderate or above on the Clinical Global Impression- Severity Scale

Exclusion Criteria:

  • Subjects with positive pregnancy test, swallowing difficulty, and/or presenting with active psychosis or mania will be excluded
  • Subjects currently taking guanfacine extended release
  • Patients with lactose intolerance
  • 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

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: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Placebo
Other: Placebo
Placebo will be administered concurrently with GXR during trials.
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
Initial dose for all participants will be 1mg per day. If the medication is well tolerated, the dose can be raised to 2 mg until day 28 and increased to 3 mg 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 timepoint, the study will be unblinded.and subjects will continue treatment for 8 weeks.
Other Names:
  • Intuniv

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression- Improvement change from baseline to week 16
Time Frame: 16 Weeks
Clinical Global Impression-Improvement is a 7 item scale. A rating of 0=not assessed, 1= very much improved, 2= much improved, 3=minimally improved, 4= no change, 5= minimally worse, 6= much worse, and 7= very much worse. Scores after "4" indicate a decreasing health outcome. Positive clinical response will be determined by a rating of 1= very much improved or 2= Much improved at the end of the blinded trial.
16 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
A change in Aberrant Behavior Checklist from baseline to week 16
Time Frame: 16 Weeks
Aberrant Behavior Checklist is a 58 item survey. Items are rated on 4 point scale, "0" indicates no problem, "3" indicates major problem. Higher scores are associated with greater severity. The scales are subdivided into 5 subscales: hyperactivity, lethargy, stereotypical behavior, irritability, and inappropriate speech.
16 Weeks
A change in Self-Injury Trauma Scale from baseline to week 16
Time Frame: 16 Weeks
Self Injury Trauma Scale is divided into three parts. Part 1 is an observation of healed injuries and identifying self injurious behaviors. Part 2 is subdivided into three parts number, type, and severity. Number is based on the number of wounds 1=one wound (common in a mild cases but rare in a severe case) 2=two or four wounds (common) and 3=five or more wounds (rare). Type is categorical and used to differentiate between abrasion/laceration and contusion. Injury severity is scored on a 3 item scale. "1" represents the least severe option and "3" represents the most severe option. Injury severity is broken down between type. Part 3 is the Estimate of Current Risk. It is assessed on a subjective basis with labels such as "mild", "moderate", and "severe" accompanied by descriptions of the observed state of the anatomy. Higher scores are associated with greater severity.
16 Weeks
A change in Modified Overt Aggression Scale from baseline to week 16
Time Frame: 16 Weeks
Modified Overt Aggression Scale is a four-part behavior rating scale used to evaluate and document the "frequency and severity" of aggressive episodes. The rating scale is made up of four categories: verbal aggression, aggression against objects, aggression against self, and aggression against others. Each part is rated on a 5 point scale, "0" indicates no aggression, "4" indicates the most aggressive option. Higher scores are associated with greater severity.
16 Weeks

Collaborators and Investigators

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

Sponsor

Maimonides Medical Center

Investigators

  • Principal Investigator: Deepan Singh, MD, Maimonides Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

December 17, 2020

Primary Completion (Anticipated)

January 18, 2024

Study Completion (Anticipated)

January 18, 2024

Study Registration Dates

First Submitted

December 12, 2022

First Submitted That Met QC Criteria

December 12, 2022

First Posted (Actual)

December 20, 2022

Study Record Updates

Last Update Posted (Actual)

March 15, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-11-03-MMC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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