Risperidone for the Treatment of Huntington's Disease Involuntary Movements

Phase 2

Completed

Conditions: Huntington Disease
Chorea

Interventions: Drug: Risperidone
Device: BioStamp nPoint device

Registration Number: NCT04201834

Lead Sponsor: University of Rochester

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Risperidone	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.
Risperidone	BioStamp nPoint device	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Unified Huntington's Disease (HD) Rating Scale Total Maximal Chorea (UHDRS TMC) Score	Baseline to week 12	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Unified Huntington's Disease (HD) Rating Scale Total Motor Score	Baseline to week 12	The UHDRS total motor score measures motor function. The score ranges from 0-124 . Higher total scores indicate worse motor function.
Change From Baseline in Mean Epworth Sleepiness Scale (ESS)	Baseline to week 12	This tool measures excessive daytime sleepiness with higher scores indicating worse health outcomes. The scale range is 0 to 24.
Change From Baseline in Mean Barnes Akathisia Scale Global Clinical Assessment of Akathisia Item Score	Baseline to week 12	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.
Number of Participants With a Change in Clinical Global Impression of Change (CGI)	Baseline to week 12	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).
Number of Participants With a Change in Patient Global Impression of Change (PGI)	Baseline to week 12	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).
Change From Baseline in Mean Quantitative Motor (Q-Motor) Right Hand Speeded Finger Tapping Variability	Baseline to week 8	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.
Change From Baseline in Mean Short Problem Behavior Assessment (Short PBA-S) Irritability and Aggression Score	Baseline to week 12	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.
Columbia Suicide Severity Rating Scale( C-SSRS)	Baseline to week 12	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.
Change From Baseline in Mean Apathy Scale Score	Baseline to week 12	This tool measures the presence and severity of apathy. The range is 0 to 42 with higher scores indicating worse health outcomes
Change From Baseline in Mean Hospital Anxiety and Depression Scale-Depression Score	Baseline to week 12	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.
Change From Baseline in Mean Montreal Cognitive Assessment	Baseline to week 12	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.
Change From Baseline in Mean Unified Huntington's Disease (HD) Rating Scale Independence Scale Score	Baseline to week 12	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.
Change From Baseline in Mean Hospital Anxiety and Depression Scale-Anxiety Score	Baseline to week 12	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.
Change From Baseline in MC10-Assessed Mean Gait Cadence	Screening to Week 8	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.