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

NCT ID: NCT05657860

Last Updated: 2024-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-17
• Study Completion Date: 2023-12-16

Brief Summary

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.

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.

Conditions

Prader-Willi Syndrome; Aggression; Self-Injurious Behavior; Pathologic Processes; Behavioral Symptoms; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Obesity; Overnutrition; Nutrition Disorders; Antihypertensive Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Skin-Picking

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Group Type: SHAM_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo will be administered concurrently with GXR during trials.

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.

Group Type: EXPERIMENTAL

Guanfacine Extended Release

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo

Placebo will be administered concurrently with GXR during trials.

Intervention Type: OTHER

Other Intervention Names

Intuniv

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maimonides Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Deepan Singh, MD

Role: PRINCIPAL_INVESTIGATOR

Maimonides Medical Center

Locations

Maimonides Medical Center

Brooklyn, New York, United States

Countries

United States

References

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Other Identifiers

2020-11-03-MMC

Identifier Type: -

Identifier Source: org_study_id