A Pilot Study Assessing Impulsivity in Patients With Huntington's Disease on Xenazine (Tetrabenazine)

The purpose of this research study is to see if tetrabenazine, which is commonly used to treat Huntington's Disease (HD), reduces the problems of impulsivity that are common in patients with HD. Investigators will also see how the medicine affects aspects of thinking and mood.

Study Overview

• Status: Recruiting
• Conditions: Huntington's Disease
• Intervention / Treatment: Drug: Tetrabenazine

Detailed Description

This study is an open-label assessment of behavioral symptoms including depression, impulsivity, and suicidal ideations in patients prior to, and after, taking a stable dose of TBZ for Huntington's disease. All subjects will be evaluated with tests of depression (Beck Depression Scale), impulsivity (QUIP, BIS-11, and computerized impulsivity scales), and suicidal ideation (Columbia Suicide Scale) as a safety measure before they actually start taking TBZ. Since there is a significant lack of awareness of emotional and cognitive symptoms (anosagnosia) in patients with HD, collateral sources will be asked to fill out similar questionnaires based on their knowledge and observation of the patient. Patients and collaterals will be asked to return to the clinic for an identical evaluation plus adverse events, after they have been on a stable dose of TBZ for 4 weeks, which would be 8 ± 1 week after initiating TBZ. Patients will be titrated over 3-5 weeks to best dose as determined by the investigator, up to a maximum of 75 mg/day. As patients are titrating, there will be several telephone contacts conducted. The initial dose will be 12.5 mg BID. Best dose will be largely determined by adverse events and subjective efficacy. Determination of best dose will include two scheduled phone calls and others as needed. Other medications will remain stable between visits.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: William G Ondo, MD; Phone Number: 713-363-8390; Email: wondo@houstonmethodist.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Methodist Neurological Institute
      • Contact: William Ondo, MD; Phone Number: 713-363-8390; Email: wondo@houstonmethodist.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For HUntington's Disease (HD) patients only--Definite HD as indicated by positive gene testing or typical symptoms in the context of family history of HD.
• A moderate degree of impulsivity as measured by the Barrat Impulsivity Scale (BIS). (>65)
• Must be symptomatic in the opinion of the investigator. Standard clinical criteria for symptomatic HD will be employed, any motor signs c/w HD, usually chorea.
• Patient is cognitively alert and able to answer/understand.

Exclusion Criteria:

• Patient requires the assistance of another person to walk, or is non-ambulatory.
• Patient is severely impaired cognitively.
• Patients taking neuroleptic (dopamine blocking) medications within the past 14 days.
• patient is actively suicidal, has untreated or inadequately treated depression, has impaired hepatic function, is taking MAO inhibitors or is taking reserpine or has been off of reserpine for less than 20 days

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: Tetrabenazine; Xenazine (tetrabenazine), pill, dosage titrated to effect, three times a day, 12 weeks	Drug: Tetrabenazine; Xenazine, pill, dose to effect, three times a day, for 12 weeks; Other Names: Xenazine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Score on the Questionnaire for Impulsive Disorders in Parkinson's Disease	A newly developed and tested tool for measuring impulsivity in PD patients.	Baseline and 8 weeks
Change in Score on the Geriatric Depression Scale	This assessment detects depressive symptoms in subjects and is a commonly used neuropsychological scale. It is less influenced by motor / somatic symptoms compared to other depression scales.	Baseline and 8 weeks
Change in Score on the Barrat Impulsivity Scale	Scale is the most widely used self-report measure of impulsive personality traits. The BIS-11 is a 30-item self-report questionnaire that is scored to yield a total score, three second-order factors, and six first-order factors.	Baseline and 8 weeks
Change in Score on the Minnesota Impulsivity Disorders Interview	This is a clinician-administered screening instrument that had shown good reliability and validity in studies of adult and adolescent psychiatric patients.	Baseline and 8 weeks
Change in Score on the Iowa Gambling Task	a widely used, but complex, neuropsychological task of executive function in which mixed outcomes (gains and losses) are experienced together, to performance on a relatively simpler descriptive task, the Cups task, which isolates adaptive decision making for achieving gains and avoiding losses. It is very predictive of impulsive personality traits	Baseline and 8 weeks
Change in Score on the Montreal Cognitive Impairment Assessment	cognitive screening test designed to assist Health Professionals for detection of mild cognitive impairment, including Alzheimer's disease.	Baseline and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Score on the United Huntington's Disease Rating Scale - Motor section	A clinical examination of various cognitive, behavioral, and motor features commonly seen in patients with HD (Huntington Study Group, 1996). This is a standardized test used in most clinical studies of HD.	Baseline and 8 weeks

Collaborators and Investigators

• Sponsor: William Ondo, MD
• Collaborators: H. Lundbeck A/S
• Investigators: Principal Investigator: William G Ondo, MD, The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: July 24, 2015
• First Submitted That Met QC Criteria: July 24, 2015
• First Posted (Estimate): July 28, 2015

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease; Impulsive Behavior; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Tetrabenazine
• Other Study ID Numbers: Pro00013929; HSC-MS-13-0878 (Other Identifier: UTHealth -Houston)

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: No
• product manufactured in and exported from the U.S.: No