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

NCT05657860 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 2020-11-03-MMC
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

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

Keywords

Adrenergic alpha-2 Receptor Agonist; Guanfacine; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impression- Improvement change from baseline to week 16

  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 Outcomes (3)

• A change in Aberrant Behavior Checklist from baseline to week 16

  16 Weeks

• A change in Self-Injury Trauma Scale from baseline to week 16

  16 Weeks

• A change in Modified Overt Aggression Scale from baseline to week 16

  16 Weeks

Study Arms (2)

Placebo

SHAM COMPARATOR

Other: Placebo

GXR

EXPERIMENTAL

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

Interventions

Guanfacine Extended Release 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.

Also known as: Intuniv

GXR

Placebo OTHER

Placebo will be administered concurrently with GXR during trials.

Placebo

Eligibility Criteria

• Age: 6 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maimonides Medical Center: lead

Study Sites (1)

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Related Publications (8)

• Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, Lane R, Lim P, Duca AR, Hough D, Thase ME, Zajecka J, Winokur A, Divacka I, Fagiolini A, Cubala WJ, Bitter I, Blier P, Shelton RC, Molero P, Manji H, Drevets WC, Singh JB. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Sep 1;76(9):893-903. doi: 10.1001/jamapsychiatry.2019.1189.

  PMID: 31166571 BACKGROUND

• Wajs E, Aluisio L, Holder R, Daly EJ, Lane R, Lim P, George JE, Morrison RL, Sanacora G, Young AH, Kasper S, Sulaiman AH, Li CT, Paik JW, Manji H, Hough D, Grunfeld J, Jeon HJ, Wilkinson ST, Drevets WC, Singh JB. Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2). J Clin Psychiatry. 2020 Apr 28;81(3):19m12891. doi: 10.4088/JCP.19m12891.

  PMID: 32316080 BACKGROUND

• Ochs-Ross R, Daly EJ, Zhang Y, Lane R, Lim P, Morrison RL, Hough D, Manji H, Drevets WC, Sanacora G, Steffens DC, Adler C, McShane R, Gaillard R, Wilkinson ST, Singh JB. Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020 Feb;28(2):121-141. doi: 10.1016/j.jagp.2019.10.008. Epub 2019 Oct 17.

  PMID: 31734084 BACKGROUND

• Ketterer MW, Brymer J, Rhoads K, Kraft P, Lovallo WR. Is aspirin, as used for antithrombosis, an emotion-modulating agent? J Psychosom Res. 1996 Jan;40(1):53-8. doi: 10.1016/0022-3999(95)00524-2.

  PMID: 8730644 BACKGROUND

• Mendlewicz J, Kriwin P, Oswald P, Souery D, Alboni S, Brunello N. Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study. Int Clin Psychopharmacol. 2006 Jul;21(4):227-31. doi: 10.1097/00004850-200607000-00005.

  PMID: 16687994 BACKGROUND

• Ng QX, Ramamoorthy K, Loke W, Lee MWL, Yeo WS, Lim DY, Sivalingam V. Clinical Role of Aspirin in Mood Disorders: A Systematic Review. Brain Sci. 2019 Oct 29;9(11):296. doi: 10.3390/brainsci9110296.

  PMID: 31671812 BACKGROUND

• Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, Weatherall A, Paal P. Ketamine: use in anesthesia. CNS Neurosci Ther. 2013 Jun;19(6):381-9. doi: 10.1111/cns.12072. Epub 2013 Mar 22.

  PMID: 23521979 BACKGROUND

• Motov S, Rockoff B, Cohen V, Pushkar I, Likourezos A, McKay C, Soleyman-Zomalan E, Homel P, Terentiev V, Fromm C. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2015 Sep;66(3):222-229.e1. doi: 10.1016/j.annemergmed.2015.03.004. Epub 2015 Mar 26.

  PMID: 25817884 BACKGROUND

MeSH Terms

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; Excoriation Disorder

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Imprinting Disorders; Overweight; Nutritional and Metabolic Diseases; Aberrant Motor Behavior in Dementia; Behavior; Social Behavior; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Body Weight; Obsessive-Compulsive Disorder; Anxiety Disorders; Disruptive, Impulse Control, and Conduct Disorders

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Deepan Singh, MD

  Maimonides Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: December 20, 2022
• Study Start: December 17, 2020
• Primary Completion: December 16, 2023
• Study Completion: December 16, 2023
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)