Back to resultsImpact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease
Primary Purpose
Huntington Disease
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Deutetrabenazine
Sponsored by
About this trial
This is an interventional treatment trial for Huntington Disease
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of HD with documented CAG repeat ≥ 37
- UHDRS total maximal chorea score of ≥ 8
- Able to walk at least 10 meters
- Medically stable outpatient, based on the investigator's judgment
- Willing and able to give written informed consent prior to performing any study procedures
- Have completed at least 10th grade
- Montreal Cognitive Assessment score ≥ 22 on screening
- Female subjects of childbearing potential agree to use an acceptable method of contraception from screening through study completion
Exclusion Criteria:
- Severe depression or suicidal ideation
- History of suicidal behavior
- Unstable or serious medical or psychiatric illness
- Renal or hepatic impairment
- Severe speech impairment or anarthria
- Inability to swallow study medication
- Women who are pregnant or breast feeding
- History of alcohol or substance abuse within the last 12 months
- Current use of VMAT2 inhibitor (tetrabenazine, deutetrabenazine, valbenazine)
- Concurrent participation in any other investigational drug trials
- EKG QTcF> 500 mse
Sites / Locations
- Vanderbilt University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Deutetrabenazine
Arm Description
The mode of administration is oral. Subjects will be started on deutetrabenazine at a dose of 6mg/day. Dosing will be up-titrated in increments of 6mg/day per week to achieve optimal chorea control.
Outcomes
Primary Outcome Measures
Sentence Intelligibility Test (SIT)
SIT is a measure of speech intelligibility that requires the participant to read aloud 11 sentences that increase in length from 5 to 10 words. Speech intelligibility is indexed in terms of percent intelligible. This is determined by calculating the mean number of correct words transcribed from the SIT transcriptions by three unfamiliar listeners and dividing this by the total number of words in the 11-sentence sample.
Motor Speech Evaluation (MSE)
The MSE will include a set of tasks described by Duffy (2013) that permit consistent rating of perceptual characteristics associated with motor speech disorders. These tasks include vowel prolongation, alternating motion rates, sequential motion rates, and contextual speech (oral reading, picture description, conversational speech). These recordings will be used to complete the perceptual assessment of speech characteristics using the Mayo Clinic classification system.
Secondary Outcome Measures
3-D optical motion capture system recording
To determine the effect of deutetrabenazine on facial movements at rest and during functional task performance (e.g., speaking, chewing) in individuals with HD, the investigators will utilize a 3-D optical motion capture system (Motion Analysis, Ltd.) consisting of six infrared Kestrel cameras with a sensor resolution of 2.2 million pixels at 2,048 x 1,088 full resolution. Facial movements will be captured by placing small (2mm) reflective spheres on each patient's jaw (right/left/center), mouth (right/left corner, upper/lower lip center), and cheeks (right/left zygomatic bone). Further, reflective markers will be placed on the forehead (right/left eyebrows, right/left forehead). Four head markers will serve as reference markers for head movement correction and transposition of all marker movement into a head-based coordinate system.
Functional Joint Kinematics Improvements
To determine the effect of deutetrabenazine on joint kinematics and spatiotemporal parameters using 3D motion analysis. Participants will be recording using the Xsens MVN Awinda motion capture system during a 10 meter walk test. Lower- and upper-limb kinematics will be recorded. Wireless sensors will be placed on the ankle, thigh, hand, forearm, bicep, and head. The velocity of the 10 meter walk can be compared to age and gender matched normative values. Gait speed correlates with functional ability, balance and confidence. Three trials are completed, and the average of the three scores is documented. This test will be completed using the 3D motion analysis system.
Four Square Step Test (FSST)
The FSST assesses dynamic balance stepping over objects forward, backwards, and sideways. The individual is required to step as fast as possible into each square, requiring the individual to step objects in varying directions. Two tests are completed, with the best time documented as the score.
Functional Gait Assessment (FGA)
The FGA assesses dynamic balance during gait and provides objective information regarding risk of falling. The FGA consists of ten items scored from 0-3, with a maximum total score of 30 points. Items include normal walking, walking with speed changes, walking with head turns, pivot turns, obstacle negotiation, tandem walking, walking with eyes closed, walking backward, and negotiating stairs. Scores less than 23/30 are predictive of falls.
Full Information
NCT ID
NCT04713982
First Posted
January 6, 2021
Last Updated
December 30, 2022
Sponsor
Vanderbilt University Medical Center
Collaborators
Teva Branded Pharmaceutical Products R&D, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04713982
Brief Title
Impact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease
Official Title
Impact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 19, 2021 (Actual)
Primary Completion Date
August 30, 2023 (Anticipated)
Study Completion Date
April 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
Teva Branded Pharmaceutical Products R&D, Inc.
4. Oversight
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.
Yes
5. Study Description
Brief Summary
Examine the effects of deutetrabenazine on functional speech and gait impairment
Detailed Description
This is a two-year, prospective, single-arm study examining the effects of deutetrabenazine on functional speech and gait impairment. Participants will undergo comprehensive evaluations of speech production, fine motor skills, gait, and balance both before and after the initiation of deutetrabenazine. The investigators will utilize a variety of standardized, well-validated assessments as well as 3D motion analysis of both speech and gait parameters to determine the functional impact of deutetrabenazine on speech and motor performance.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Deutetrabenazine
Arm Type
Experimental
Arm Description
The mode of administration is oral. Subjects will be started on deutetrabenazine at a dose of 6mg/day. Dosing will be up-titrated in increments of 6mg/day per week to achieve optimal chorea control.
Intervention Type
Drug
Intervention Name(s)
Deutetrabenazine
Other Intervention Name(s)
Austedo
Intervention Description
Maximum dose of 48mg/day or up to 36 mg/d if receiving a strong CYP2D6 inhibitor
Primary Outcome Measure Information:
Title
Sentence Intelligibility Test (SIT)
Description
SIT is a measure of speech intelligibility that requires the participant to read aloud 11 sentences that increase in length from 5 to 10 words. Speech intelligibility is indexed in terms of percent intelligible. This is determined by calculating the mean number of correct words transcribed from the SIT transcriptions by three unfamiliar listeners and dividing this by the total number of words in the 11-sentence sample.
Time Frame
Up to 10 weeks
Title
Motor Speech Evaluation (MSE)
Description
The MSE will include a set of tasks described by Duffy (2013) that permit consistent rating of perceptual characteristics associated with motor speech disorders. These tasks include vowel prolongation, alternating motion rates, sequential motion rates, and contextual speech (oral reading, picture description, conversational speech). These recordings will be used to complete the perceptual assessment of speech characteristics using the Mayo Clinic classification system.
Time Frame
Up to 10 weeks
Secondary Outcome Measure Information:
Title
3-D optical motion capture system recording
Description
To determine the effect of deutetrabenazine on facial movements at rest and during functional task performance (e.g., speaking, chewing) in individuals with HD, the investigators will utilize a 3-D optical motion capture system (Motion Analysis, Ltd.) consisting of six infrared Kestrel cameras with a sensor resolution of 2.2 million pixels at 2,048 x 1,088 full resolution. Facial movements will be captured by placing small (2mm) reflective spheres on each patient's jaw (right/left/center), mouth (right/left corner, upper/lower lip center), and cheeks (right/left zygomatic bone). Further, reflective markers will be placed on the forehead (right/left eyebrows, right/left forehead). Four head markers will serve as reference markers for head movement correction and transposition of all marker movement into a head-based coordinate system.
Time Frame
Up to 10 weeks
Title
Functional Joint Kinematics Improvements
Description
To determine the effect of deutetrabenazine on joint kinematics and spatiotemporal parameters using 3D motion analysis. Participants will be recording using the Xsens MVN Awinda motion capture system during a 10 meter walk test. Lower- and upper-limb kinematics will be recorded. Wireless sensors will be placed on the ankle, thigh, hand, forearm, bicep, and head. The velocity of the 10 meter walk can be compared to age and gender matched normative values. Gait speed correlates with functional ability, balance and confidence. Three trials are completed, and the average of the three scores is documented. This test will be completed using the 3D motion analysis system.
Time Frame
Up to 10 weeks
Title
Four Square Step Test (FSST)
Description
The FSST assesses dynamic balance stepping over objects forward, backwards, and sideways. The individual is required to step as fast as possible into each square, requiring the individual to step objects in varying directions. Two tests are completed, with the best time documented as the score.
Time Frame
Up to 10 Weeks
Title
Functional Gait Assessment (FGA)
Description
The FGA assesses dynamic balance during gait and provides objective information regarding risk of falling. The FGA consists of ten items scored from 0-3, with a maximum total score of 30 points. Items include normal walking, walking with speed changes, walking with head turns, pivot turns, obstacle negotiation, tandem walking, walking with eyes closed, walking backward, and negotiating stairs. Scores less than 23/30 are predictive of falls.
Time Frame
Up to 10 weeks
Other Pre-specified Outcome Measures:
Title
Communication Effectiveness Survey
Description
The CES is an 8-item patient reported outcome measure that is designed to rate communication effectiveness in individuals with dysarthria. Each of the items presents a communication situation (e.g., talking on the phone with a familiar listener; talking while driving in a car, etc.) and the participant rates his or her perceived ability to communicate in that situation on a scale from "1" (not at all effective) to "4" (very effective).
Time Frame
Up to 10 weeks
Title
Nine-Hole Peg Test
Description
The Nine-Hole Peg Test is an assessment of fine motor coordination that measures each hand individually. The final score reported is the time required to place and remove nine pegs with each hand. Results are compared to age and gender matched normative values. This test will assess the impact of chorea on fine motor movements and dexterity.
Time Frame
Up to 10 weeks
Title
10 Meter Walk test
Description
With the 10 Meter Walk Test, velocity can be compared to age and gender matched normative values. Gait speed correlates with functional ability, balance and confidence. Three trials are completed, and the average of the three scores is documented. This test will be completed using the 3D motion analysis system.
Time Frame
Up to 10 Weeks
Title
Health Status
Description
The investigators will be using the short-form 36 (SF-36) which is a generic patient-reported outcome measure that quantifies perceived health status. It is used as a measure of health-related quality of life. Sub sections include physical function, role limitations secondary to physical problems, general health perceptions, vitality, social functioning, role limitations due to emotional problems, mental health, and health transition. Participants respond referring to their perceived health over the past 4 weeks.
Time Frame
Up to 10 weeks
Title
The Functional Assessment of Chronic Illness Therapy (FACIT) scale
Description
The FACIT scale has been validated in a number of chronic conditions, including cancer, Parkinson's disease, multiple sclerosis, and HIV/AIDS (Webster 2003). It includes assessments of physical, social, emotional, and functional well-being and is available in multiple condition- and treatment-specific versions. The FACIT scale is sensitive to changes in individual participants over time and can also be used to compare patient populations.
Time Frame
Up to 10 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of HD with documented CAG repeat ≥ 37
UHDRS total maximal chorea score of ≥ 8
Able to walk at least 10 meters
Medically stable outpatient, based on the investigator's judgment
Willing and able to give written informed consent prior to performing any study procedures
Have completed at least 10th grade
Montreal Cognitive Assessment score ≥ 22 on screening
Female subjects of childbearing potential agree to use an acceptable method of contraception from screening through study completion
Exclusion Criteria:
Severe depression or suicidal ideation
History of suicidal behavior
Unstable or serious medical or psychiatric illness
Renal or hepatic impairment
Severe speech impairment or anarthria
Inability to swallow study medication
Women who are pregnant or breast feeding
History of alcohol or substance abuse within the last 12 months
Current use of VMAT2 inhibitor (tetrabenazine, deutetrabenazine, valbenazine)
Concurrent participation in any other investigational drug trials
EKG QTcF> 500 mse
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amy E Brown, MD
Phone
615.936.0060
Email
amy.brown@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy E Brown, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy E Brown, MD
Phone
615-936-0060
Email
amy.brown@vumc.org
First Name & Middle Initial & Last Name & Degree
Amy E Brown, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Impact of Deutetrabenazine on Functional Speech and Gait Dynamics in Huntington Disease
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