Risperidone for the Treatment of Huntington's Disease Involuntary Movements

Study Overview
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Brief Summary
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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.

Official Title
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Risperidone for the Treatment of Huntington's Disease Chorea

Conditions
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Huntington Disease, Chorea

Intervention / Treatment
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* Drug: Risperidone
* Device: BioStamp nPoint device


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risperidone<br>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<br>* capsule or tablet, 0.5 mg<br>Device: BioStamp nPoint device<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean Unified Huntington's Disease (HD) Rating Scale Total Maximal Chorea (UHDRS TMC) score | The UHDRS is a validated assessment of HD. The complete total maximal chorea score is a subset of the overall motor assessment and measures maximal chorea with scores from 0 to 4 with higher scores indicating more chorea. | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean Unified Huntington's Disease (HD)Rating Scale total scores | The total UHDRS measures motor, cognitive, behavioral, functional, and total functional capacity. The score ranges from 0 to 161. Higher total scores indicate worse health outcomes. | Screening to week 12 | 
| 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 | 
| mean Barnes Akathisia Scale | This tool measures drug-induced akathisia by objective observation and subjective questions. The scale range is 0 to 12 with higher scores indicating akathisia. | Baseline to week 12 | 
| mean 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). Higher score indicates no change. | Baseline to week 12 | 
| mean patient global impression of change | 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). A higher score indicates no change. | Baseline to week 12 | 
| Chorea Index as measured by BioStamp nPoint device | The average amount of chorea measured using the BioStamp nPoint device will be determined. Higher score indicates greater degree of chorea. | Screening to week 8 | 
| Q-Motor (quantitative motor) assessments of chorea | 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. | Baseline to week 8 | 
| Short Problem Behavior Assessment form (Short PBA-S) | This tool measures different behavioural 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 is 0 to 132. Higher scores indicate worse health outcomes. | Baseline to week 12 | 
| 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 | 
| mean Apathy Scale | 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 | 
| mean hospital anxiety and depression scale | This is a self-reported scale that measures anxiety and depression and ranges from 0 to 21 with a lower score indicating better health outcomes. | Baseline to week 12 | 
| mean Montreal Cognitive assessment | The Montreal Cognitive assessment (MoCA) measures mild cognitive dysfunction. The total possible score is 30 points; a score of 26 or above is considered normal. | Baseline visit only | 
| mean Unified Huntington's Disease(HD) Rating Scale Independence rating | the UHDRS component measures level of current independence. It ranges from 10 to 100 with higher scores indicating greater degree of independence. | screening to week 12 |