Risperidone for the Treatment of Huntington's Disease Involuntary Movements

Risperidone for the Treatment of Huntington's Disease Chorea

The purpose of this study is to assess the safety and benefit of risperidone for the treatment of chorea (involuntary movements) in Huntington's disease. Risperidone is commonly used in clinical practice to treat chorea, however, it has not been approved by the Food and Drug Administration (FDA) to treat chorea. This study will examine 1) whether the investigators see MRI changes with risperidone treatment and 2) whether sensors applied to the participants body can measure chorea and detect changes in chorea.

Study Overview

• Status: Completed
• Conditions: Huntington Disease; Chorea
• Intervention / Treatment: Drug: Risperidone; Device: BioStamp nPoint device

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14618
      • URMC Neurology; 919 Westfall Rd, Building C, Suite 100

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Manifest HD (Diagnostic Confidence Level 4 + CAG repeat ≥ 37 or family history of HD)
• UHDRS Total Maximal Chorea (TMC) ≥ 8
• UHDRS Total Functional Capacity ≥ 5
• Subject willing and able to provide written informed consent OR legally authorized representative provides written informed consent and subject provides assent*
• Between 18 and 65 years of age

Exclusion Criteria:

• Use of antipsychotic, levodopa, dopamine agonist, monoamine oxidase inhibitor or other disallowed medication in the 30 days prior to the baseline visit (see Section 4.2.5)*
• Prior non-response to risperidone or intolerability to risperidone (in the investigator's opinion)
• Allergy or hypersensitivity to risperidone
• Dysphagia that in the investigator's opinion would preclude participation in the study
• Active suicidal ideation or psychiatric condition that in the investigator's opinion would preclude study participation
• QTc > 460 msec for women and QTc > 450 msec for men on 12-lead EKG
• History of cardiac arrhythmia or congenital long QT syndrome
• Significant renal impairment (creatinine clearance < 30 mL/min as estimated by the Cockgroft-Gault formula) or hepatic impairment (AST or ALT > 2.5 times upper limit of normal OR alkaline phosphatase or total bilirubin > 2 times upper limit of normal)
• Active drug or alcohol abuse or dependence
• Pregnant or breast-feeding
• Any contraindication to MRI (e.g. pacemakers, aneurysm clips, metallic prostheses, shrapnel fragments, claustrophobia)
• History of active (clinically significant) skin disorder that would interfere with sensor adherence
• History of allergic response to adhesives
• Pacemaker, AICD, or other implantable stimulator
• Use of an investigational drug in the 30 days prior to the baseline visit
• Inability to complete study activities, as determined by the study team
• Clinically significant parkinsonism as determined by expert investigator assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Risperidone; Participants will initiate risperidone 0.5 mg nightly the day after the baseline visit. Dose assessment will occur at pre-specified intervals during the titration phase (week 2, 3, 4, 6, 7). The investigator will increase the dose by 0.5 mg at the week 2, week 3, week 4, and week 6 visits until either optimal chorea benefit has been obtained, an intolerable adverse event occurs, or the maximum allowable dose (3.0 mg) is reached.

Drug: Risperidone; capsule or tablet, 0.5 mg; Device: BioStamp nPoint device; MC10 has developed the BioStamp nPointTM, a FDA 510(k) cleared medical device. This multimodal, reusable and rechargeable biosensor uses flexible and stretchable electronics to enable unobtrusive wear on the body and monitoring in the home. The sensors have accelerometry, gyroscopy, and ECG/EMG capabilities. A docking station enables wireless recharging and data collection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Unified Huntington's Disease (HD) Rating Scale Total Maximal Chorea (UHDRS TMC) Score	The UHDRS is a validated assessment of HD. The TMC score is a subset of the overall motor assessment and measures maximal chorea in seven different body regions. The TMC score ranges from 0 to 28 with higher scores indicating more chorea.	Baseline to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Columbia Suicide Severity Rating Scale( C-SSRS)	The number of participants expressing suicidal ideations will be determined by answering yes to any of the following questions: Have you wished you were dead or wished you could go to sleep and not wake up?, Have you actually had any thoughts of killing yourself?, Have you been thinking about how you might do this?, Have you had these thoughts and had some intention of acting on them?, Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan? All questions require only a yes or no response. There is no numerical scoring or rating.	Baseline to week 12
Change From Baseline in Mean Unified Huntington's Disease (HD) Rating Scale Total Motor Score	The UHDRS total motor score measures motor function. The score ranges from 0-124 . Higher total scores indicate worse motor function.	Baseline to week 12
Change From Baseline in Mean Epworth Sleepiness Scale (ESS)	This tool measures excessive daytime sleepiness with higher scores indicating worse health outcomes. The scale range is 0 to 24.	Baseline to week 12
Change From Baseline in Mean Barnes Akathisia Scale Global Clinical Assessment of Akathisia Item Score	This tool measures drug-induced akathisia by objective observation and subjective questions. The Global Clinical Assessment of Akathisia Item score ranges from 0 to 5 with higher scores indicating more severe akathisia.	Baseline to week 12
Number of Participants With a Change in Clinical Global Impression of Change (CGI)	This tool is a observer-rated scale that measures impression of severity and change. It is rated on a 7 point scale from 1(very much improved) to 7 (very much worse).	Baseline to week 12
Number of Participants With a Change in Patient Global Impression of Change (PGI)	This tool is a patient related scale that measures impression of change on a 7 point scale from 1 (very much improved) to 7 (very much worse).	Baseline to week 12
Change From Baseline in Mean Quantitative Motor (Q-Motor) Right Hand Speeded Finger Tapping Variability	The Q-motor tool uses force transducers and a grip device to measure chorea completing four different tasks that assess fine motor finger and foot tapping speed, pronation/supination and gripping strength. With finger tapping inter-onset interval variability, which is measured in seconds, lower values indicate less irregularity and higher values more irregularity.	Baseline to week 8
Change From Baseline in Mean Short Problem Behavior Assessment (Short PBA-S) Irritability and Aggression Score	This tool measures different behavioral problems which are rated for both severity and frequency on a 5 point scale; severity and frequency ratings are then multiplied to provide an overall score for each symptom. The range for the composite Irritability and Aggression score is 0-32. Higher scores indicate greater difficulties.	Baseline to week 12
Change From Baseline in Mean Apathy Scale Score	This tool measures the presence and severity of apathy. The range is 0 to 42 with higher scores indicating worse health outcomes	Baseline to week 12
Change From Baseline in Mean Hospital Anxiety and Depression Scale-Depression Score	This is a self-reported scale that measures anxiety and depression. The Depression sub-score ranges from 0 to 21 with higher scores indicating more depressive symptoms.	Baseline to week 12
Change From Baseline in Mean Montreal Cognitive Assessment	The Montreal Cognitive assessment (MoCA) measures cognitive function (attention and concentration, executive functions, memory, language, visuospatial skills, conceptual thinking, calculations, and orientation). The score ranges from 0 to 30. Lower scores indicate worse cognitive function.	Baseline to week 12
Change From Baseline in Mean Unified Huntington's Disease (HD) Rating Scale Independence Scale Score	The UHDRS Independence Scale measures level of current functional independence. The score ranges from 10 to 100 with higher scores indicating a higher degree of functional independence.	Baseline to week 12
Change From Baseline in Mean Hospital Anxiety and Depression Scale-Anxiety Score	This is a self-reported scale that measures anxiety and depression. The Anxiety sub-score ranges from 0 to 21 with higher scores indicating more anxiety symptoms.	Baseline to week 12
Change From Baseline in MC10-Assessed Mean Gait Cadence	MC10 BioStamp nPoint is a wearable biosensor system with accelerometry, gyroscopy, and ECG/EMG capabilities that provides various gait metrics. Gait cadence refers to steps per minute. Higher values indicate more steps per minute.	Screening to Week 8

Collaborators and Investigators

• Sponsor: University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Actual): December 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: December 13, 2019
• First Posted (Actual): December 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Huntington Disease; Chorea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Serotonin Antagonists; Serotonin Agents; Antipsychotic Agents; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 4443

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No