Functional and Structural Imaging and Motor Control in Spinocerebellar Ataxia

NCT02488031 | Completed

• 2 other identifiers: IRB201500202-NR21NS094946
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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).

Conditions

Spinocerebellar Ataxia

Keywords

SCA, dysmetria

Outcome Measures

Primary Outcomes (1)

• 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).

  Change from Baseline to 1 month

Secondary Outcomes (3)

• International Cooperative Ataxia Rating Scale(ICARS) Assessment

  Change from Baseline to 1 month

• Change in Motor Unit Discharge Rate Variability

  Change from Baseline to 1 month

• Change in Blood-oxygen-level-dependent(BOLD) Activity of Motor Cortex

  Change from Baseline to 1 month

Study Arms (2)

Error-reduction

EXPERIMENTAL

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.

Behavioral: Error-reduction; Behavioral: International Cooperative Ataxia Rating Scale; Behavioral: Scale for the Assessment and Rating of Ataxia; Behavioral: Beck Depression Inventory, 2nd Ed; Behavioral: Stroop; Behavioral: Purdue Pegboard; Behavioral: Brief Test of Attention; Behavioral: 6-minute Walk; Behavioral: Hand Grip Dynamometer; Behavioral: Montreal Cognitive Assessment; Behavioral: Physical Performance Function; Behavioral: Biomechanical Assessments of Dysmetria; Behavioral: Neurophysiological assessment of brain activity; Behavioral: Biomechanical gait analysis

Best Medical Management

EXPERIMENTAL

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.

Behavioral: International Cooperative Ataxia Rating Scale; Behavioral: Scale for the Assessment and Rating of Ataxia; Behavioral: Beck Depression Inventory, 2nd Ed; Behavioral: Stroop; Behavioral: Purdue Pegboard; Behavioral: Brief Test of Attention; Behavioral: 6-minute Walk; Behavioral: Hand Grip Dynamometer; Behavioral: Montreal Cognitive Assessment; Behavioral: Physical Performance Function; Behavioral: Biomechanical Assessments of Dysmetria; Behavioral: Neurophysiological assessment of brain activity; Behavioral: Biomechanical gait analysis

Interventions

Error-reduction BEHAVIORAL

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.

Error-reduction

International Cooperative Ataxia Rating Scale BEHAVIORAL

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.

Best Medical Management; Error-reduction

Scale for the Assessment and Rating of Ataxia BEHAVIORAL

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.

Also known as: SARA

Best Medical Management; Error-reduction

Beck Depression Inventory, 2nd Ed BEHAVIORAL

This is a 21 question self-report inventory for measuring severity of depression.

Best Medical Management; Error-reduction

Stroop BEHAVIORAL

This test measures selective attention and cognitive flexibility through reading aloud of color names or color of the print.

Best Medical Management; Error-reduction

Purdue Pegboard BEHAVIORAL

This test consists of a series of timed hand coordination and dexterity tasks.

Best Medical Management; Error-reduction

Brief Test of Attention BEHAVIORAL

A cognitive test assessing focus and attention.

Best Medical Management; Error-reduction

6-minute Walk BEHAVIORAL

This test consists on a timed 6-minute walk test to evaluate how much distance is covered.

Best Medical Management; Error-reduction

Hand Grip Dynamometer BEHAVIORAL

This tests measures hand grip strength.

Best Medical Management; Error-reduction

Montreal Cognitive Assessment BEHAVIORAL

This test is used to assess cognitive abilities.

Best Medical Management; Error-reduction

Physical Performance Function BEHAVIORAL

This test consists of a series of physical activities used to evaluate speed, coordination, and ease of movement.

Best Medical Management; Error-reduction

Biomechanical Assessments of Dysmetria BEHAVIORAL

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.

Best Medical Management; Error-reduction

Neurophysiological assessment of brain activity BEHAVIORAL

Neurophysiology will be assessed by monitoring brain activity using Task-based fMRI and motor unit pool activity using a specialized EMG system.

Best Medical Management; Error-reduction

Biomechanical gait analysis BEHAVIORAL

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).

Best Medical Management; Error-reduction

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of South Florida: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32611, United States

Location

Related Publications (12)

• Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum. 2005;4(1):2-6. doi: 10.1080/14734220510007914.

  PMID: 15895552 BACKGROUND

• Manto M. Mechanisms of human cerebellar dysmetria: experimental evidence and current conceptual bases. J Neuroeng Rehabil. 2009 Apr 13;6:10. doi: 10.1186/1743-0003-6-10.

  PMID: 19364396 BACKGROUND

• Solodkin A, Gomez CM. Spinocerebellar ataxia type 6. Handb Clin Neurol. 2012;103:461-73. doi: 10.1016/B978-0-444-51892-7.00029-2.

  PMID: 21827907 BACKGROUND

• Schmitz-Hubsch T, Tezenas du Montcel S, Baliko L, Boesch S, Bonato S, Fancellu R, Giunti P, Globas C, Kang JS, Kremer B, Mariotti C, Melegh B, Rakowicz M, Rola R, Romano S, Schols L, Szymanski S, van de Warrenburg BP, Zdzienicka E, Durr A, Klockgether T. Reliability and validity of the International Cooperative Ataxia Rating Scale: a study in 156 spinocerebellar ataxia patients. Mov Disord. 2006 May;21(5):699-704. doi: 10.1002/mds.20781.

  PMID: 16450347 BACKGROUND

• Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. 1994 Nov;8(3):221-8. doi: 10.1038/ng1194-221.

  PMID: 7874163 BACKGROUND

• Reetz K, Costa AS, Mirzazade S, Lehmann A, Juzek A, Rakowicz M, Boguslawska R, Schols L, Linnemann C, Mariotti C, Grisoli M, Durr A, van de Warrenburg BP, Timmann D, Pandolfo M, Bauer P, Jacobi H, Hauser TK, Klockgether T, Schulz JB; axia Study Group Investigators. Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6. Brain. 2013 Mar;136(Pt 3):905-17. doi: 10.1093/brain/aws369. Epub 2013 Feb 18.

  PMID: 23423669 BACKGROUND

• Pasternak O, Shenton ME, Westin CF. Estimation of extracellular volume from regularized multi-shell diffusion MRI. Med Image Comput Comput Assist Interv. 2012;15(Pt 2):305-12. doi: 10.1007/978-3-642-33418-4_38.

  PMID: 23286062 BACKGROUND

• Pasternak O, Sochen N, Gur Y, Intrator N, Assaf Y. Free water elimination and mapping from diffusion MRI. Magn Reson Med. 2009 Sep;62(3):717-30. doi: 10.1002/mrm.22055.

  PMID: 19623619 BACKGROUND

• De Luca CJ, Adam A, Wotiz R, Gilmore LD, Nawab SH. Decomposition of surface EMG signals. J Neurophysiol. 2006 Sep;96(3):1646-57. doi: 10.1152/jn.00009.2006.

  PMID: 16899649 BACKGROUND

• Morton SM, Bastian AJ. Cerebellar control of balance and locomotion. Neuroscientist. 2004 Jun;10(3):247-59. doi: 10.1177/1073858404263517.

  PMID: 15155063 BACKGROUND

• Haines DE, Manto MU. Clinical symptoms of cerebellar disease and their interpretation. Cerebellum. 2007;6(4):360-74. doi: 10.1080/14734220701798199. No abstract available.

  PMID: 18041661 BACKGROUND

• Keller JL, Bastian AJ. A home balance exercise program improves walking in people with cerebellar ataxia. Neurorehabil Neural Repair. 2014 Oct;28(8):770-8. doi: 10.1177/1545968314522350. Epub 2014 Feb 13.

  PMID: 24526707 BACKGROUND

MeSH Terms

Conditions

Spinocerebellar Ataxias; Heart Arrest; Cerebellar Ataxia

Interventions

Weights and Measures; Stroop Test; Walking; Mental Status and Dementia Tests

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Investigative Techniques; Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities; Locomotion; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise; Motor Activity

Study Officials

• Evangelos Christou, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

• David Vaillancourt, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 2, 2015
• Study Start: March 1, 2016
• Primary Completion: January 17, 2019
• Study Completion: January 17, 2019
• Last Updated: May 13, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)