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Functional and Structural Imaging and Motor Control in Spinocerebellar Ataxia (SCA)

Primary Purpose

Spinocerebellar Ataxia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Error-reduction
International Cooperative Ataxia Rating Scale
Scale for the Assessment and Rating of Ataxia
Beck Depression Inventory, 2nd Ed
Stroop
Purdue Pegboard
Brief Test of Attention
6-minute Walk
Hand Grip Dynamometer
Montreal Cognitive Assessment
Physical Performance Function
Biomechanical Assessments of Dysmetria
Neurophysiological assessment of brain activity
Biomechanical gait analysis
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinocerebellar Ataxia focused on measuring SCA, dysmetria

Eligibility Criteria

21 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • DNA diagnosis of SCA1, SCA3, or SCA6
  • phenotype consistent with the DNA diagnosis
  • ability to walk 7 meters
  • the age of 21-85 years
  • capable of providing informed consent and complying with the trial procedures

Exclusion Criteria:

  • Known recessive, X-linked or mitochondrial ataxias or any other type of ataxia
  • Concomitant disorder(s) that affect ataxia measures used in this study
  • Cognitive status on the Montreal Cognitive Assessment < 24
  • Patients who have any type of implanted electrical device (such as a cardiac pacemaker or a neurostimulator), or a certain type of metallic clip in their body (i.e., an aneurysm clip in the brain), and are not eligible for participation in the MRI portion of the study
  • Individuals who are claustrophobic
  • Women who are or might be pregnant and nursing mothers
  • Individuals with psychiatric disorders or dementia, along with other neurological and orthopedic problems that impair hand movements and walking

Sites / Locations

  • University of Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Error-reduction

Best Medical Management

Arm Description

The participants in the error-reduction group will participate in a 4-week home-based training intervention during the month between their pre- and post-test visits. During pre- and post- training visits, Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA), Purdue Pegboard, Brief Test of Attention, 6-minute Walk, Hand Grip Dynamometer, Physical Performance Function, Digit Span, SARA, Montreal Cognitive Assessment, Beck Depression Inventory 2nd Ed, Stroop and biomechanical gait analysis tests will be administered. Also biomechanical assessments of dysmetria and neurophysiological assessment of brain activity will be conducted to evaluate the impact of the training on SCA individuals.

The participants in the best medical management group will undergo identical testing sessions (two visits one month apart) as those in the error-reducing group but will not receive the 4-week error reducing intervention. They will be administered the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA) assessments and the following tests: Purdue Pegboard, Brief Test of Attention, 6-minute Walk, Hand Grip Dynamometer, Physical Performance Function, Digit Span, SARA, Montreal Cognitive Assessment, Beck Depression Inventory 2nd Ed, Stroop and biomechanical gait. Biomechanical assessments of dysmetria and neurophysiological assessment of brain activity will be conducted at both visits.

Outcomes

Primary Outcome Measures

Change in the Location of the Movement Endpoint Relative to the Target in the Motor Task
Assessment of the subject's ability to stay on target during the motor task. The task is a goal-directed movement that aims to match a spatial target in a specific time(time target).

Secondary Outcome Measures

International Cooperative Ataxia Rating Scale(ICARS) Assessment
The ICARS is an assessment of the ataxia severity. The ICARS score is the total sum of the sub scores on specific movements and ranges from 0 to 100, with a score of 100 being indicative of the most severely affected outcome.
Change in Motor Unit Discharge Rate Variability
Amount of motor unit activity occurring during the Electromyography(EMG) task. Lower amount of variability is better. The change reflects the difference in values between the pre- and post-training sessions. The discharge rate variability will change by percent.
Change in Blood-oxygen-level-dependent(BOLD) Activity of Motor Cortex
Results of blood-oxygen-level-dependent contrast imaging as analyzed from functional Magnetic Resonance Imaging(fMRI). More colors indicates more excitement of the motor cortex.

Full Information

First Posted
June 30, 2015
Last Updated
May 9, 2019
Sponsor
University of Florida
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), University of South Florida
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1. Study Identification

Unique Protocol Identification Number
NCT02488031
Brief Title
Functional and Structural Imaging and Motor Control in Spinocerebellar Ataxia
Acronym
SCA
Official Title
Dysmetria in Motor Function in SCA: Mechanisms and Rehabilitation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
January 17, 2019 (Actual)
Study Completion Date
January 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), University of South Florida

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this research study is to investigate how the brain and motor behavior changes both in individuals with spinocerebellar ataxia and healthy individuals, and to assess whether a therapeutic intervention reduces levels of uncoordinated movement and improves motor function in spinocerebellar ataxia (SCA).
Detailed Description
Thirty individuals who have been diagnosed with either Spinocerebellar Ataxia - 1 (SCA1), Spinocerebellar Ataxia - 3 (SCA3), or Spinocerebellar Ataxia - 6 (SCA6) will be recruited for this study. Participants will be randomly assigned to a best medical management (BMM / control) group and an error-reduction group. All participants will visit the lab twice for testing one month apart. Participants in the control group will not train between the pre- and post-test time. The error-reduction intervention will be a 4-week home-based program. Investigators will use a novel, custom designed computer interface. Participants will perform goal-directed movements with each leg to targets in a 3D virtual environment designed to emphasize accurate movements. The goal-directed leg movements (similar to leg press) will be performed seated and require hip, knee, and ankle joint control. Leg movement will be detected using the LeapMotion sensor (Leap Motion Inc. San Francisco, CA), a device that supports hand, and finger / tool motions as input, similar to a mouse, but requiring no contact. Spatial endpoint errors will be quantified in 3D space by comparing the endpoint location of the foot trajectory (extending from the big toe) and the virtual location of the target. Time endpoint errors will be quantified by comparing the timing of the foot trajectory and the required time to target. The length of the intervention will be 4 weeks. Each participant will train 4 days a week for ~1 hour per day. Within a week the task difficulty will increase by changing the presentation of the target from a predictable to an unpredictable location, by increasing movement speed requirements and by changing target size. Targets will be made predictable by identifying them prior to the cue for movement onset (target turning green). Specifically, there will be a flashing dotted line around the target prior to the target turning green. Targets will be made unpredictable by not providing any indication of the target location prior to the target turning green. Movement speed will be quantified from the voluntary movement onset of the leg (no reaction time) to the movement end.The movement speed requirements will be increased within a week and participants will learn to execute faster movements from the feedback after each trial. The size of the target will be progressively reduced during the 4 weeks. All individuals in the study will receive a pre- and post-test assessment using the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA). The individual sections of the ICARS (e.g. Kinetic section) and SARA will be quantified. In addition, leg dysmetria will be quantified using a custom-made goal-directed movement protocol. Specifically, participants will perform unloaded ankle dorsiflexion movements and attempt to reach a space-time target. The primary outcomes will be position and time errors. Biomechanics of overground walking in SCA will be monitored using the APDM mobility lab (APDM, Inc. Mobility Lab, Oregon, USA). Participants will wear APDM's wireless sensors on the hands, legs, trunk and forehead and walk overground a distance of 7 meters for 2 minutes. APDM quantifies 80 common biomechanical outcomes of gait (e.g. stride length variability). The neurophysiology of SCA will be quantified with functional Magnetic Resonance Imaging (fMRI) and motor unit pool activity. Brain activity will be quantified with task-based fMRI using a 32-channel head coil. During fMRI force tasks, ankle dorsiflexion will be measured from the most affected lower limb using customized fiber optic sensors, as has been done in the past. Real-time feedback of force performance will be provided to the subject. During the rest blocks, subjects will fixate on a stationary target but do not produce force. During task blocks, subjects will complete 2 second pulse-hold contractions to 15% maximum voluntary contraction(MVC) of ankle dorsiflexion followed by 1 second of rest. There will be 10 pulses per block. The knee will be supported by a pillow to flex the knee so that the forces applied by the ankle do not cause head movement.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinocerebellar Ataxia
Keywords
SCA, dysmetria

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Error-reduction
Arm Type
Experimental
Arm Description
The participants in the error-reduction group will participate in a 4-week home-based training intervention during the month between their pre- and post-test visits. During pre- and post- training visits, Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA), Purdue Pegboard, Brief Test of Attention, 6-minute Walk, Hand Grip Dynamometer, Physical Performance Function, Digit Span, SARA, Montreal Cognitive Assessment, Beck Depression Inventory 2nd Ed, Stroop and biomechanical gait analysis tests will be administered. Also biomechanical assessments of dysmetria and neurophysiological assessment of brain activity will be conducted to evaluate the impact of the training on SCA individuals.
Arm Title
Best Medical Management
Arm Type
Experimental
Arm Description
The participants in the best medical management group will undergo identical testing sessions (two visits one month apart) as those in the error-reducing group but will not receive the 4-week error reducing intervention. They will be administered the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA) assessments and the following tests: Purdue Pegboard, Brief Test of Attention, 6-minute Walk, Hand Grip Dynamometer, Physical Performance Function, Digit Span, SARA, Montreal Cognitive Assessment, Beck Depression Inventory 2nd Ed, Stroop and biomechanical gait. Biomechanical assessments of dysmetria and neurophysiological assessment of brain activity will be conducted at both visits.
Intervention Type
Behavioral
Intervention Name(s)
Error-reduction
Intervention Description
During this time participants will use a novel, custom designed computer interface to perform goal-directed movements with each leg in a 3D virtual environment designed to emphasize accurate movements. Leg movement will be detected using the LeapMotion sensor and we will quantify time endpoint errors by comparing the timing of the foot trajectory and the required time to target. The error-reduction intervention will be a 4-week home-based program. Each participant will train 4 days a week for approximately 1 hours per day. Within a week, the task difficulty will increase by changing the presentation of the targets to be more unpredictable and by increasing movement speed.
Intervention Type
Behavioral
Intervention Name(s)
International Cooperative Ataxia Rating Scale
Intervention Description
The ICARS is an assessment of the ataxia severity. The ICARS score is the total sum of the sub scores on specific movements and ranges from 0 to 100, with a score of 100 being indicative of the most severely affected outcome.
Intervention Type
Behavioral
Intervention Name(s)
Scale for the Assessment and Rating of Ataxia
Other Intervention Name(s)
SARA
Intervention Description
The SARA is an assessment of the ataxia severity. The SARA score is the total sum of the sub scores on specific movements and ranges from 0 to 100, with a score of 100 being indicative of the most severely affected outcome.
Intervention Type
Behavioral
Intervention Name(s)
Beck Depression Inventory, 2nd Ed
Intervention Description
This is a 21 question self-report inventory for measuring severity of depression.
Intervention Type
Behavioral
Intervention Name(s)
Stroop
Intervention Description
This test measures selective attention and cognitive flexibility through reading aloud of color names or color of the print.
Intervention Type
Behavioral
Intervention Name(s)
Purdue Pegboard
Intervention Description
This test consists of a series of timed hand coordination and dexterity tasks.
Intervention Type
Behavioral
Intervention Name(s)
Brief Test of Attention
Intervention Description
A cognitive test assessing focus and attention.
Intervention Type
Behavioral
Intervention Name(s)
6-minute Walk
Intervention Description
This test consists on a timed 6-minute walk test to evaluate how much distance is covered.
Intervention Type
Behavioral
Intervention Name(s)
Hand Grip Dynamometer
Intervention Description
This tests measures hand grip strength.
Intervention Type
Behavioral
Intervention Name(s)
Montreal Cognitive Assessment
Intervention Description
This test is used to assess cognitive abilities.
Intervention Type
Behavioral
Intervention Name(s)
Physical Performance Function
Intervention Description
This test consists of a series of physical activities used to evaluate speed, coordination, and ease of movement.
Intervention Type
Behavioral
Intervention Name(s)
Biomechanical Assessments of Dysmetria
Intervention Description
Dysmetria will be assessed using a custom-made goal-directed movement protocol where participant perform unloaded limb movement tasks and attempt to reach a space-time target. During these task muscle activity is monitored using Electromyography (EMG) recording.
Intervention Type
Behavioral
Intervention Name(s)
Neurophysiological assessment of brain activity
Intervention Description
Neurophysiology will be assessed by monitoring brain activity using Task-based fMRI and motor unit pool activity using a specialized EMG system.
Intervention Type
Behavioral
Intervention Name(s)
Biomechanical gait analysis
Intervention Description
Participants will wear APDM's wireless sensors on the hands, legs, trunk and forehead and walk overground a distance of 7 m for 2 minutes. APDM quantifies 80 common biomechanical outcomes of gait (e.g. stride length variability).
Primary Outcome Measure Information:
Title
Change in the Location of the Movement Endpoint Relative to the Target in the Motor Task
Description
Assessment of the subject's ability to stay on target during the motor task. The task is a goal-directed movement that aims to match a spatial target in a specific time(time target).
Time Frame
Change from Baseline to 1 month
Secondary Outcome Measure Information:
Title
International Cooperative Ataxia Rating Scale(ICARS) Assessment
Description
The ICARS is an assessment of the ataxia severity. The ICARS score is the total sum of the sub scores on specific movements and ranges from 0 to 100, with a score of 100 being indicative of the most severely affected outcome.
Time Frame
Change from Baseline to 1 month
Title
Change in Motor Unit Discharge Rate Variability
Description
Amount of motor unit activity occurring during the Electromyography(EMG) task. Lower amount of variability is better. The change reflects the difference in values between the pre- and post-training sessions. The discharge rate variability will change by percent.
Time Frame
Change from Baseline to 1 month
Title
Change in Blood-oxygen-level-dependent(BOLD) Activity of Motor Cortex
Description
Results of blood-oxygen-level-dependent contrast imaging as analyzed from functional Magnetic Resonance Imaging(fMRI). More colors indicates more excitement of the motor cortex.
Time Frame
Change from Baseline to 1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: DNA diagnosis of SCA1, SCA3, or SCA6 phenotype consistent with the DNA diagnosis ability to walk 7 meters the age of 21-85 years capable of providing informed consent and complying with the trial procedures Exclusion Criteria: Known recessive, X-linked or mitochondrial ataxias or any other type of ataxia Concomitant disorder(s) that affect ataxia measures used in this study Cognitive status on the Montreal Cognitive Assessment < 24 Patients who have any type of implanted electrical device (such as a cardiac pacemaker or a neurostimulator), or a certain type of metallic clip in their body (i.e., an aneurysm clip in the brain), and are not eligible for participation in the MRI portion of the study Individuals who are claustrophobic Women who are or might be pregnant and nursing mothers Individuals with psychiatric disorders or dementia, along with other neurological and orthopedic problems that impair hand movements and walking
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Evangelos Christou, PhD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Vaillancourt, PhD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Functional and Structural Imaging and Motor Control in Spinocerebellar Ataxia

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